John Rotrosen, M.D.

Buprenorphine-naloxone maintenance following release from jail
Lee, Joshua D; Grossman, Ellie; Truncali, Andrea; Rotrosen, John; Rosenblum, Andrew; Magura, Stephen; Gourevitch, Marc N
2012 Jan;33(1):40-47, Substance abuse
ABSTRACT Primary care is understudied as a reentry drug and alcohol treatment setting. This study compared treatment retention and opioid misuse among opioid-dependent adults seeking buprenorphine/naloxone maintenance in an urban primary care clinic following release from jail versus community referrals. Postrelease patients were either (a) induced to buprenorphine in-jail as part of a clinical trial, or (b) seeking buprenorphine induction post release. From 2007 to 2008, N = 142 patients were new to primary care buprenorphine: n = 32 postrelease; n = 110 induced after community referral and without recent incarceration. Jail-released patients were more likely African American or Hispanic and uninsured. Treatment retention rates for postrelease (37%) versus community (30%) referrals were similar at 48 weeks. Rates of opioid positive urines and self-reported opioid misuse were also similar between groups. Postrelease patients in primary care buprenorphine treatment had equal treatment retention and rates of opioid abstinence versus community-referred patients
— id: 150570, year: 2012, vol: 33, page: 40, stat: Journal Article,

Barriers to providing health services for HIV/AIDS, hepatitis C virus infection and sexually transmitted infections in substance abuse treatment programs in the United States
Bini, Edmund J; Kritz, Steven; Brown, Lawrence S Jr; Robinson, Jim; Alderson, Don; Rotrosen, John
2011 Apr;30(2):98-109, Journal of addictive diseases
We sought to identify barriers to offering services for HIV/AIDS, hepatitis C virus, and sexually transmitted infections in substance abuse treatment programs. We surveyed treatment program administrators and clinicians within the National Drug Abuse Treatment Clinical Trials Network to evaluate the availability of medical and non-medical services for patients with or at risk for acquiring these infections. A substantial proportion of programs do not offer services (particularly medical services) for these infections. The most commonly cited barriers were funding, health insurance benefits, patient acceptance, and staff training. The findings highlight a missed opportunity to positively impact these infectious disease epidemics
— id: 134683, year: 2011, vol: 30, page: 98, stat: Journal Article,

Program, counselor, and patient variability in the alliance: A multilevel study of the alliance in relation to substance use outcomes
Crits-Christoph, Paul; Hamilton, Jessica L; Ring-Kurtz, Sarah; Gallop, Robert; McClure, Bridget; Kulaga, Agatha; Rotrosen, John
2011 Jun;40(4):405-413, Journal of substance abuse treatment
We explored patient, therapist, and program variability in the alliance in relation to drug and alcohol use during treatment, and whether alliance mediates the relation of program characteristics to drug/alcohol use. Data (N = 1,613 patients) were drawn from a randomized clinical trial investigating the efficacy of an intervention that provided alliance and outcome feedback to 112 counselors across 20 community-based outpatient substance abuse treatment clinics in the northeast United States. Program characteristics were measured using the Organization Readiness for Change scale. Using multilevel modeling, we found that alliance was related to both drug and alcohol use during the past week at the patient and program levels of analysis, but not the counselor level. Several program characteristics were related to average drug and alcohol use. The alliance was not a mediator of these relationships. Program variability in the alliance is important to the alliance-outcome relationship in the treatment of substance abuse. Better outcomes can be achieved by improving both organizational functioning and the patient-counselor alliance
— id: 133357, year: 2011, vol: 40, page: 405, stat: Journal Article,

Reduced Interhemispheric Resting State Functional Connectivity in Cocaine Addiction
Kelly C; Zuo XN; Gotimer K; Cox CL; Lynch L; Brock D; Imperati D; Garavan H; Rotrosen J; Castellanos FX; Milham MP
2011 Apr 1;69(7):684-692, Biological psychiatry
BACKGROUND: Models of cocaine addiction emphasize the role of disrupted frontal circuitry supporting cognitive control processes. However, addiction-related alterations in functional interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. We examined interhemispheric resting-state functional connectivity (RSFC) in cocaine dependence using a recently validated approach, voxel-mirrored homotopic connectivity. METHODS: We compared interhemispheric RSFC between 25 adults (aged 35.0 +/- 8.8) meeting DSM-IV criteria for cocaine dependence within the past 12 months but currently abstaining (>2 weeks) from cocaine and 24 healthy comparisons (35.1 +/- 7.5), group-matched on age, sex, education, and employment status. RESULTS: We observed reduced prefrontal interhemispheric RSFC in cocaine-dependent participants relative to control subjects. Further analyses demonstrated a striking cocaine-dependence-related reduction in interhemispheric RSFC among nodes of the dorsal attention network, comprising bilateral lateral frontal, medial premotor, and posterior parietal areas. Further, within the cocaine-dependent group, RSFC within the dorsal attention network was associated with self-reported attentional lapses. CONCLUSIONS: Our findings provide further evidence of an association between chronic exposure to cocaine and disruptions within large-scale brain circuitry supporting cognitive control. We did not detect group differences in diffusion tensor imaging measures, suggesting that alterations in the brain's functional architecture associated with cocaine exposure can be observed in the absence of detectable abnormalities in the white matter microstructure supporting that architecture
— id: 122711, year: 2011, vol: 69, page: 684, stat: Journal Article,

Screening and interventions for substance use in dental clinics: A survey of dentists on current clinical practices, policies and barriers
McNeely J.; Wright S.; Rotrosen J.; Shelley D.; Matthews A.G.; Buccholz M.; Curro F.
2011 ;4(2):110-110, Clinical & Translational Science
OBJECTIVES/SPECIFIC AIMS: Substance use has substantial effects on oral health, and dental visits provide an opportunity to address substance use disorders. We surveyed dentists to learn whether they might play a role in substance use screening and interventions. METHODS/STUDY POPULATION: All dentists active in the PEARL dental practice-based research network were invited to complete a web-based survey in summer 2010. The 41-item survey assessed clinic policies and dentists' practices, attitudes, and perception of barriers regarding screening, counseling, and referrals for substance use. RESULTS/ANTICIPATED RESULTS: One hundred forty-three dentists completed the survey (68% response rate). Almost all respondents felt it was important to screen patients for tobacco (99%), alcohol (92%) and illicit drug (93%) use, though actual screening rates were much lower. Counseling or referrals were infrequently provided for users of alcohol (29%) and illicit drugs (25%), but were more common for tobacco (63%). The most frequently identified barrier to addressing substance use was insufficient knowledge/training. Other barriers were lack of referral sites, staff resistance, and time constraints. If reimbursement were available, many dentists said they would offer counseling and assistance for tobacco (67%), alcohol (52%), and illicit drugs (48%); an affirmative response was significantly more likely among the 43 dentists who saw Medicaid patients (p < 0.01). DISCUSSION/SIGNIFICANCE OF IMPACT: Dentists recognize the importance of screening for substance use, but lack the clinical training and systems that might allow them to intervene. If these barriers were reduced, dentists could be willing partners in addressing substance use disorders
— id: 142065, year: 2011, vol: 4, page: 110, stat: Journal Article,

Smoking Cessation Treatment among Patients in Community-Based Substance Abuse Rehabilitation Programs: Exploring Predictors of Outcome as Clues Toward Treatment Improvement
Reid, Malcolm S; Jiang, Huiping; Fallon, Bryan; Sonne, Susan; Rinaldi, Paul; Turrigiano, Eva; Arfken, Cynthia; Robinson, James; Rotrosen, John; Nunes, Edward V
2011 Sep;37(5):472-478, American journal of drug & alcohol abuse
Background: Predictors of smoking cessation (SC) treatment outcome were explored in a multisite clinical trial of SC treatment at community-based, outpatient, substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment Clinical Trials Network. Objectives: To explore baseline demographic and clinical predictors of abstinence during treatment. Methods: Cigarette smokers from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned to SC treatment as an adjunct to substance abuse treatment as usual or to substance abuse treatment as usual. SC treatment consisted of group counseling (weeks 1-8) plus transdermal nicotine patch treatment (21 mg/day, weeks 1-6; 14 mg/day, weeks 7-8). Demographic and clinical predictors of smoking abstinence were evaluated among those patients assigned to the active SC condition (N = 153) using logistic regression. Results: Abstinence during treatment was positively associated with younger age, Hispanic or Caucasian (as opposed to African American) ethnicity/race, employment or student status, fewer cigarettes per day at baseline, lower severity of the primary substance problem at baseline, and higher methadone doses (among the subsample in methadone treatment). Conclusions and Scientific Significance: During future efforts to improve SC treatments among drug- and alcohol-dependent patients, consideration should be given to adequate treatment to reduce the severity of the primary drug or alcohol problem, tailoring treatments for patients with greater severity of smoking and of the primary substance problem, and culturally sensitive interventions. Analysis of predictors of outcome may be a useful tool for treatment development
— id: 136946, year: 2011, vol: 37, page: 472, stat: Journal Article,

Substance abuse treatment as HIV prevention: more questions than answers
Brown, Lawrence S Jr; Kritz, Steven; Bini, Edmund J; Louie, Ben; Robinson, Jim; Alderson, Donald; Rotrosen, John
2010 Dec;102(12):1183-1191, Journal of the National Medical Association
This report examines associations between the availability of human immunodeficiency virus (HIV)-related health services in substance abuse treatment programs and characteristics of the programs and the patients they serve. In a cross-sectional, descriptive design and via a validated survey, program administrators within the National Drug Abuse Treatment Clinical Trials Network provided information on program characteristics, patient characteristics (rates of risky sexual and drug behaviors and HIV infection), and the availability of 31 different HIV-related health services. Of 319 programs, 84% submitted surveys. Service availability rates ranged from: 10% (pneumococcal vaccination) to 86% (drug testing) for the 6 HIV-related services offered to all patients, 13% (Pap smear for women) to 54% (tuberculin skin testing) for the 6 services offered to new patients, 2% (sterile injection equipment) to 64% (male condoms) for the 4 risk-reduction services, 37% (Pap smear for women) to 61% (tuberculin skin testing) for the 11 biological assessments offered to HIV-positive patients, and 33% (medical treatments) to 52% (counseling) for the 4 other services offered to HIV-positive patients. The availability of these HIV-related services was associated with clinical settings, the types of addiction treatment services, the rates of risky drug and sexual behaviors, and HIV infection rates among patients. Availability of such services was below published guidelines. While the results provide another basis for the infection-related prevention benefits of substance abuse treatment, the variability in the availability of HIV-related health care deserves further study and has health policy implications in determining how to utilize substance abuse treatment in reducing drug-related HIV transmission
— id: 131661, year: 2010, vol: 102, page: 1183, stat: Journal Article,

A randomized controlled study of a web-based performance improvement system for substance abuse treatment providers
Crits-Christoph, Paul; Ring-Kurtz, Sarah; McClure, Bridget; Temes, Christina; Kulaga, Agatha; Gallop, Robert; Forman, Robert; Rotrosen, John
2010 Apr;38(3):251-262, Journal of substance abuse treatment
We report here the results of a randomized, controlled trial evaluating the efficacy of a semiautomated performance improvement system ('patient feedback') that enables real-time monitoring of patient outcomes in outpatient substance abuse treatment clinics. The study involved 118 clinicians working at 20 community-based outpatient substance abuse treatment clinics in the northeast United States. Ten clinics received 12 weeks of the patient feedback performance improvement intervention, and 10 clinics received no intervention during the 12 weeks. More than 1,500 patients provided anonymous ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol use. There was no evidence of an intervention effect on the primary drug and alcohol use scales. There was also no evidence of an intervention effect on secondary measures of therapeutic alliance. Clinician-rated measures of organizational functioning and job satisfaction also showed no intervention effect. Possible insights from these findings and alternative methods of utilizing feedback reports to enhance clinical outcomes are proposed
— id: 120733, year: 2010, vol: 38, page: 251, stat: Journal Article,

Extended-release naltrexone for treatment of alcohol dependence in primary care
Lee, Joshua D; Grossman, Ellie; DiRocco, Danae; Truncali, Andrea; Hanley, Kathleen; Stevens, David; Rotrosen, John; Gourevitch, Marc N
2010 Jul;39(1):14-21, Journal of substance abuse treatment
The feasibility of using extended-release injectable naltrexone (XR-NTX) to treat alcohol dependence in routine primary care settings is unknown. An open-label, observational cohort study evaluated 3-month treatment retention, patient satisfaction, and alcohol use among alcohol-dependent patients in two urban public hospital medical clinics. Adults seeking treatment were offered monthly medical management (MM) and three XR-NTX injections (380 mg, intramuscular). Physician-delivered MM emphasized alcohol abstinence, medication effects, and accessing mutual help and counseling resources. Seventy-two alcohol-dependent patients were enrolled; 90% (65 of 72) of eligible subjects received the first XR-NTX injection; 75% (49 of 65) initiating treatment received the second XR-NTX injection; 62% (40 of 65), the third. Among the 56% (n = 40) receiving three injections, median drinks per day decreased from 4.1 (95% confidence interval = 2.9-6) at baseline to 0.5 (0-1.7) during Month 3. Extended-release naltrexone delivered in a primary care MM model appears a feasible and acceptable treatment for alcohol dependence
— id: 111657, year: 2010, vol: 39, page: 14, stat: Journal Article,

Multisite effectiveness trials of treatments for substance abuse and co-occurring problems: have we chosen the best designs?
Nunes, Edward V; Ball, Samuel; Booth, Robert; Brigham, Gregory; Calsyn, Donald A; Carroll, Kathleen; Feaster, Daniel J; Hien, Denise; Hubbard, Robert L; Ling, Walter; Petry, Nancy M; Rotrosen, John; Selzer, Jeffrey; Stitzer, Maxine; Tross, Susan; Wakim, Paul; Winhusen, Theresa; Woody, George
2010 Jun;38 Suppl 1:S97-112, Journal of substance abuse treatment
Multisite effectiveness trials such as those carried out in the National Drug Abuse Treatment Clinical Trials Network (CTN) are a critical step in the development and dissemination of evidence-based treatments because they address how such treatments perform in real-world clinical settings. As Brigham et al. summarized in a recent article (G. S. Brigham, D. J. Feaster, P. G. Wakim, & C. L. Dempsey C. L., 2009), several possible experimental designs may be chosen for such effectiveness trials. These include (a) a new treatment intervention (Tx) is compared to an existing mode of community based treatment as usual (TAU): Tx versus TAU; (b) a new intervention is added to TAU and compared to TAU alone: Tx + TAU versus TAU; or (c) a new intervention is added to TAU and compared to a control condition added to TAU: Tx + TAU versus control + TAU. Each of these designs addresses a different question and has different potential strengths and weaknesses. As of December 2009, the primary outcome paper had been published for 16 of the multisite randomized clinical trials conducted in the CTN, testing various treatments for drug abuse, HIV risk behavior, or related problems. This paper systematically examines, for each of the completed trials, the experimental design type chosen and its original rationale, the main findings of the trial, and the strengths and weaknesses of the design in hindsight. Based on this review, recommendations are generated to inform the design of future effectiveness trials on treatments for substance abuse, HIV risk, and other behavioral health problems
— id: 109782, year: 2010, vol: 38 Suppl 1, page: S97, stat: Journal Article,

The relationship between depression and smoking cessation outcomes in treatment-seeking substance abusers
Sonne, Susan C; Nunes, Edward V; Jiang, Huiping; Tyson, Clare; Rotrosen, John; Reid, Malcolm S
2010 Mar;19(2):111-118, American journal on addictions
The National Drug Abuse Treatment Clinical Trials Network (CTN) recently completed a randomized, open label trial comparing treatment as usual (TAU) combined with nicotine patches plus cognitive behavioral group counseling for smoking cessation (n = 153) to TAU alone (n = 72) for patients enrolled in treatment programs for drug or alcohol dependence, who were interested in quitting smoking. This report is a secondary analysis evaluating the effect of depressive symptomatology (n = 70) or history of depression (n = 110) on smoking cessation outcomes. A significant association was seen between measures of depression and difficulty quitting cigarettes. Specifically, there was a greater probability for smoking abstinence for those with lower baseline Beck Depression Inventory II (BDI-II) scores. These data suggest that evaluation and treatment of depressive symptoms may play an important role in improving smoking cessation outcomes. (Am J Addict 2010;00:1-8)
— id: 109282, year: 2010, vol: 19, page: 111, stat: Journal Article,

Screening and imputed prevalence of ADHD in adult patients with comorbid substance use disorder at a residential treatment facility
Adler, Lenard A; Guida, Frank; Irons, Shirley; Rotrosen, John; O'Donnell, Katherine
2009 Sep;121(5):7-10, Postgraduate medicine
BACKGROUND: Although attention deficit/hyperactive disorder (ADHD) is a common comorbidity in individuals who are diagnosed with substance use disorder (SUD), little data currently exist on the utility of screening tools in large samples of adults with SUD in inpatient treatment and the prevalence of ADHD in this population. The aims of this study were to assess the screen positive rate on the Adult ADHD Self Report Scale (ASRS) v.1.1 Screener in a large sample of adults being treated for SUD in a residential treatment facility (RTF) and to establish the imputed prevalence of adult ADHD. METHODS: Adults with SUD who were either newly admitted (abstinent for < 1 week) or in treatment in the RTF (abstinent < 3 months) were administered the ASRS v.1.1 Screener. Adults who screened positive on the ASRS v1.1 Screener (>or= 4/6 significant items) were then administered the Adult Clinician Diagnostic Scale (ACDS) v.1.2 to establish a diagnosis of ADHD and the positive predictive value (PPV) in this population. The imputed prevalence of adult ADHD was calculated based on the known rate of ADHD in the screened positive cohort and a calculated rate of ADHD in the screened negative sample based on prior studies of the ASRS v1.1 Screener in community-based and managed care samples. RESULTS: 1064 adults were screened via the ASRS v.1.1 Screener, with 92 screening positive (8.6% had >or= 4 significant items present). Fifty-three of those who screened positive were diagnosed as having adult ADHD (PPV = 57.6%). The imputed prevalence of adult ADHD in this population was 7.5%. CONCLUSIONS: The PPV for the ASRS v1.1 Screener for adult ADHD in this sample of adults with SUD was similar to that observed in a prior study of a managed care sample, but was somewhat less than that observed in the community-based sample. The imputed prevalence rate for comorbid ADHD in this study of adults with SUD in a RTF was similar to, but slightly lower than the prevalence rate of ADHD in patients with any SUD observed in the community-based sample
— id: 104357, year: 2009, vol: 121, page: 7, stat: Journal Article,

Disparities in Health Services for HIV/AIDS, Hepatitis C Virus, and Sexually Transmitted Infections: Role of Substance Abuse Treatment Programs
Brown, Lawrence S; Kritz, Steven; Muhammad, Adashima; Bini, Edmund J; Goldsmith, R Jeffrey; Robinson, Jim; Alderson, Donald; Hasin, Deborah S; Rotrosen, John
2009 Jun;3(2):95-102, Journal of addiction medicine : JAM
OBJECTIVES: This report focused upon the availability of infection-related health services in substance abuse treatment programs with and without addiction services tailored for special populations (women and non-white populations). METHODS: In a cross-sectional, descriptive design, treatment program administrators across the United States within the National Drug Abuse Treatment Clinical Trials Network provided information on program characteristics, the availability of infection-related services (four medical services and three non-medical services for HIV, HCV, and STI), and barriers to providing infection-related services. RESULTS: Of 319 programs, 269 submitted surveys (84% response rate). Of these, 80% provided addiction services for special populations. Programs providing addiction services designed for at least one special population, were more likely to provide infection-related health services, especially HIV-related education (94% versus 85%, p = 0.05) and patient counseling (76% versus 60%, p = 0.03) and were more likely to include outpatient addiction services (86% versus 57%, p<0.001) and outreach and support services (92% versus 70%, p=0.01). Barriers to providing infection-related services included funding (cited by 48.3% to 74.7% of programs), health insurance (cited by 28.9% to 60.8% of programs), and patient acceptance (cited by 23.2% to 54.3% of programs). CONCLUSIONS: Despite many barriers, infection-related healthcare is available in programs with addiction treatment services tailored for special populations, especially for African Americans and Latino Americans. Tailoring substance abuse treatment along with reducing barriers to infection-related care represent public health interventions with potential to reduce the burdens and disparities associated with these infections
— id: 138357, year: 2009, vol: 3, page: 95, stat: Journal Article,

Extended-Release Naltrexone Injectable Suspension for Treatment of Alcohol Dependence in Urban Primary Care
Lee, J. D.; Grossman, E.; DiRocco, D.; Truncali, A.; Rotrosen, J.; Stevens, D.; Gourevitch, M. N.
2009 OCT ;30(1):85-85, Substance abuse
— id: 114203, year: 2009, vol: 30, page: 85, stat: Journal Article,

Heroin addiction in African Americans: a hypothesis-driven association study
Levran, O; Londono, D; O'Hara, K; Randesi, M; Rotrosen, J; Casadonte, P; Linzy, S; Ott, J; Adelson, M; Kreek, MJ
2009 JUL ;8(5):531-540, Genes, brain & behavior
Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify gene variants associated with heroin addiction in African Americans. The emphasis was on genes involved in reward modulation, behavioral control, cognitive function, signal transduction and stress response. We have performed a case-control association analysis by screening with 1350 variants of 130 genes. The sample consisted of 202 former severe heroin addicts in methadone treatment and 167 healthy controls with no history of drug abuse. Single nucleotide polymorphism (SNP), haplotype and multi-SNP genotype pattern analyses were performed. Seventeen SNPs showed point-wise significant association with heroin addiction (nominal P < 0.01). These SNPs are from genes encoding several receptors: adrenergic (ADRA1A), arginine vasopressin (AVPR1A), cholinergic (CHRM2), dopamine (DRD1), GABA-A (GABRB3), glutamate (GRIN2A) and serotonin (HTR3A) as well as alcohol dehydrogenase (ADH7), glutamic acid decarboxylase (GAD1 and GAD2), the nucleoside transporter (SLC29A1) and diazepam-binding inhibitor (DBI). The most significant result of the analyses was obtained for the GRIN2A haplotype G-A-T (rs4587976-rs1071502-rs1366076) with protective effect (P-uncorrected = 9.6E- 05, P-corrected = 0.058). This study corroborates several reported associations with alcohol and drug addiction as well as other related disorders and extends the list of variants that may affect the development of heroin addiction. Further studies will be necessary to replicate these associations and to elucidate the roles of these variants in drug addiction vulnerability
— id: 101089, year: 2009, vol: 8, page: 531, stat: Journal Article,

Substance abuse treatment clinician opinions and infectious disease service delivery
Tracy, Kathlene; Brown, Lawrence S; Kritz, Steven; Alderson, Donald; Robinson, Jim; Bini, Edmund J; Levy, Michael; Calsyn, Donald; Rieckmann, Traci; Fuller, Bret; McAuliffe, Pat; Rotrosen, John
2009 ;28(1):8-12, Journal of addictive diseases
Substance abuse treatment programs are an important platform for delivery of services for infectious diseases associated with drug and alcohol use. However, important components of infectious disease care are not universally provided. Clinician training often focuses on information about infectious diseases and less attention is paid to provider opinions and attitudes that may be barriers to providing infectious diseases services. In a national multi-site trial conducted by the National Drug Abuse Treatment Clinical Trials Network (CTN), we investigated the relationship between clinician opinions and the delivery of services for human immunodeficiency virus, hepatitis C virus, and sexually transmitted infections in substance abuse treatment settings. Survey data were collected from 1,723 clinicians at 269 CTN treatment programs. Clinician opinion was found to be significantly related to infectious disease service delivery. Implications for training are discussed
— id: 95039, year: 2009, vol: 28, page: 8, stat: Journal Article,

Cingulate-precuneus interactions: a new locus of dysfunction in adult attention-deficit/hyperactivity disorder
Castellanos, F Xavier; Margulies, Daniel S; Kelly, Clare; Uddin, Lucina Q; Ghaffari, Manely; Kirsch, Andrew; Shaw, David; Shehzad, Zarrar; Di Martino, Adriana; Biswal, Bharat; Sonuga-Barke, Edmund J S; Rotrosen, John; Adler, Lenard A; Milham, Michael P
2008 Feb 1;63(3):332-337, Biological psychiatry
BACKGROUND: Pathophysiologic models of attention-deficit/hyperactivity disorder (ADHD) have focused on frontal-striatal circuitry with alternative hypotheses relatively unexplored. On the basis of evidence that negative interactions between frontal foci involved in cognitive control and the non-goal-directed 'default-mode' network prevent attentional lapses, we hypothesized abnormalities in functional connectivity of these circuits in ADHD. METHODS: Resting-state blood oxygen level-dependent functional magnetic resonance imaging (fMRI) scans were obtained at 3.0-Tesla in 20 adults with ADHD and 20 age- and sex-matched healthy volunteers. RESULTS: Examination of healthy control subjects verified presence of an antiphasic or negative relationship between activity in dorsal anterior cingulate cortex (centered at x = 8, y = 7, z = 38) and in default-mode network components. Group analyses revealed ADHD-related compromises in this relationship, with decreases in the functional connectivity between the anterior cingulate and precuneus/posterior cingulate cortex regions (p < .0004, corrected). Secondary analyses revealed an extensive pattern of ADHD-related decreases in connectivity between precuneus and other default-mode network components, including ventromedial prefrontal cortex (p < 3 x 10(-11), corrected) and portions of posterior cingulate (p < .02, corrected). CONCLUSIONS: Together with prior unbiased anatomic evidence of posterior volumetric abnormalities, our findings suggest that the long-range connections linking dorsal anterior cingulate to posterior cingulate and precuneus should be considered as a candidate locus of dysfunction in ADHD
— id: 76108, year: 2008, vol: 63, page: 332, stat: Journal Article,

States and substance abuse treatment programs: funding and guidelines for infection-related services
Kritz, Steven; Brown, Lawrence S Jr; Goldsmith, R Jeffrey; Bini, Edmund J; Robinson, Jim; Alderson, Donald; Novo, Patricia; Rotrosen, John
2008 May;98(5):824-826, American journal of public health. AJPH
Community-based substance abuse treatment programs provide HIV, hepatitis C virus, and sexually transmitted infection services. To explore how state funding and guidelines affect practice, we surveyed state agency administrators and substance abuse treatment program administrators and clinicians regarding 8 infection-related services. Although state funding for infection-related services is widely available, substance abuse treatment programs do not always access it. Substance abuse treatment program guidelines are clearer in states that have written guidelines. Improved communication between state agencies and substance abuse treatment programs may enhance service
— id: 95145, year: 2008, vol: 98, page: 824, stat: Journal Article,

Genetic susceptibility to heroin addiction: a candidate gene association study
Levran, O; Londono, D; O'Hara, K; Nielsen, DA; Peles, E; Rotrosen, J; Casadonte, P; Linzy, S; Randesi, M; Ott, J; Adelson, M; Kreek, MJ
2008 OCT ;7(7):720-729, Genes, brain & behavior
Heroin addiction is a chronic complex disease with a substantial genetic contribution. This study was designed to identify genetic variants that are associated with susceptibility to develop heroin addiction by analyzing 1350 variants in 130 candidate genes. All subjects had Caucasian ancestry. The sample consisted of 412 former severe heroin addicts in methadone treatment, and 184 healthy controls with no history of drug abuse. Nine variants, in six genes, showed the lowest nominal P values in the association tests (P < 0.01). These variants were in noncoding regions of the genes encoding the mu (OPRM1; rs510769 and rs3778151), kappa (OPRK1; rs6473797) and delta (OPRD1; rs2236861, rs2236857 and rs3766951) opioid receptors; the neuropeptide galanin (GAL; rs694066); the serotonin receptor subtype 3B (HTR3B; rs3758987) and the casein kinase 1 isoform epsilon (CSNK1E; rs1534891). Several haplotypes and multilocus genotype patterns showed nominally significant associations (e.g. OPRM1; P = 0.0006 and CSNK1E; P = 0.0007). Analysis of a combined effect of OPRM1 and OPRD1 showed that rs510769 and rs2236861 increase the risk of heroin addiction (P = 0.0005). None of these associations remained significant after adjustment for multiple testing. This study suggests the involvement of several genes and variants in heroin addiction, which is worthy of future study
— id: 89775, year: 2008, vol: 7, page: 720, stat: Journal Article,

Brain macrostructural and microstructural abnormalities in cocaine dependence
Lim, Kelvin O; Wozniak, Jeffrey R; Mueller, Bryon A; Franc, Daniel T; Specker, Sheila M; Rodriguez, Craig P; Silverman, Amy B; Rotrosen, John P
2008 Jan 1;92(1-3):164-172, Drug & alcohol dependence
RATIONALE: Two previous studies have utilized diffusion tensor imaging (DTI) to examine microstructural integrity in cocaine abuse and found evidence of brain abnormalities in white matter. OBJECTIVE: Using anatomical magnetic resonance imaging (MRI), DTI, and clinical evaluation, the macrostructural and microstructural correlates of cocaine abuse were investigated. METHODS: Twenty-one men and women (mean age 42.5 and mean 18.9 years of cocaine use) and 21 age/gender-matched controls were included. Fractional anisotropy (FA) was measured in frontal white matter ROIs. Gray and white matter volumes in superior and inferior frontal regions were compared. RESULTS: DTI data revealed that cocaine users had lower FA than controls, specifically in inferior frontal white matter. FA differences were not seen in other areas. Significant volumetric differences were not seen, but both gray and white matter inferior frontal volumes trended toward smaller in the cocaine group. The data suggested that duration of use was associated with decreased gray and white matter volumes. FA and gray matter volume were correlated in cocaine users. CONCLUSIONS: Both macrostructural and microstructural abnormalities were seen in a group of cocaine abusers. Length of cocaine use was associated with severity of the brain abnormalities. Future studies of white matter tissue integrity are warranted including examination of the relationship between DTI measures and traditional volumetric measures
— id: 94534, year: 2008, vol: 92, page: 164, stat: Journal Article,

Cingulate-precuneus interactions: A new locus of dysfunction in attention-deficit/hyperactivity disorder
Milham, MP; Margulies, DS; Kelly, AMC; Uddin, LQ; Di Martino, A; Sonuga-Barke, EJS; Rotrosen, J; Adler, LA; Castellanos, FX
2008 APR 1 ;63(7):43S-43S, Biological psychiatry
— id: 78664, year: 2008, vol: 63, page: 43S, stat: Journal Article,

Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding
Palmer, Abraham A; Brown, Alan S; Keegan, Debbra; Siska, Lara DeSanti; Susser, Ezra; Rotrosen, John; Butler, Pamela D
2008 Oct 27;1237:62-74, Brain research
Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse
— id: 95291, year: 2008, vol: 1237, page: 62, stat: Journal Article,

Smoking cessation treatment in community-based substance abuse rehabilitation programs
Reid, Malcolm S; Fallon, Bryan; Sonne, Susan; Flammino, Frank; Nunes, Edward V; Jiang, Huiping; Kourniotis, Eva; Lima, Jennifer; Brady, Ron; Burgess, Cynthia; Arfken, Cynthia; Pihlgren, Eric; Giordano, Louis; Starosta, Aron; Robinson, James; Rotrosen, John
2008 Jul;35(1):68-77, Journal of substance abuse treatment
Nicotine dependence is highly prevalent among drug- and alcohol-dependent patients. A multisite clinical trial of smoking cessation (SC) treatment was performed at outpatient community-based substance abuse rehabilitation programs affiliated with the National Drug Abuse Treatment, Clinical Trials Network. Cigarette smokers (N=225) from five methadone maintenance programs and two drug and alcohol dependence treatment programs were randomly assigned in a 2:1 ratio to receive either (1) SC treatment as an adjunct to substance abuse treatment-as-usual (TAU) or (2) substance abuse TAU. Smoking cessation treatment consisted of 1 week of group counseling before the target quit date and 8 weeks of group counseling plus transdermal nicotine patch treatment (21 mg/day for Weeks 1-6 and 14 mg/day for Weeks 7 and 8) after the target quit date. Smoking abstinence rates in SC, 10%-11% during treatment and 5%-6% at the 13- and 26-week follow-up visits, were significantly better than those in TAU during treatment (p< .01). In addition, SC was associated with significantly greater reductions as compared with TAU in cigarettes smoked per day (75% reduction, p< .001), exhaled carbon monoxide levels (p< .001), cigarette craving (p< .05), and nicotine withdrawal (p< .05). Smoking cessation did not differ from TAU on rates of retention in substance abuse treatment, abstinence from primary substance of abuse, and craving for primary substance of abuse. Compliance with SC treatment, moderate at best, was positively associated with smoking abstinence rates. Smoking cessation treatment resulted in significant reductions in daily smoking and modest smoking abstinence rates without having an adverse impact on substance abuse rehabilitation when given concurrently with outpatient substance abuse treatment. Substance abuse treatment programs should not hesitate to implement SC for established patients
— id: 80814, year: 2008, vol: 35, page: 68, stat: Journal Article,

Network homogeneity reveals decreased integrity of default-mode network in ADHD
Uddin, Lucina Q; Kelly, A M Clare; Biswal, Bharat B; Margulies, Daniel S; Shehzad, Zarrar; Shaw, David; Ghaffari, Manely; Rotrosen, John; Adler, Lenard A; Castellanos, F Xavier; Milham, Michael P
2008 Mar 30;169(1):249-254, Journal of neuroscience methods
Examination of spontaneous intrinsic brain activity is drawing increasing interest, thus methods for such analyses are rapidly evolving. Here we describe a novel measure, 'network homogeneity', that allows for assessment of cohesiveness within a specified functional network, and apply it to resting-state fMRI data from adult ADHD and control participants. We examined the default mode network, a medial-wall based network characterized by high baseline activity that decreases during attention-demanding cognitive tasks. We found reduced network homogeneity within the default mode network in ADHD subjects compared to age-matched controls, particularly between the precuneus and other default mode network regions. This confirms previously published results using seed-based functional connectivity measures, and provides further evidence that altered precuneus connectivity is involved in the neuropathology of ADHD. Network homogeneity provides a potential alternative method for assessing functional connectivity of specific large-scale networks in clinical populations
— id: 76811, year: 2008, vol: 169, page: 249, stat: Journal Article,

Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature
Wilens, Timothy E; Adler, Lenard A; Adams, Jill; Sgambati, Stephanie; Rotrosen, John; Sawtelle, Robert; Utzinger, Linsey; Fusillo, Steven
2008 Jan;47(1):21-31, Journal of the American Academy of Child & Adolescent Psychiatry
OBJECTIVE: Recent studies have provided variable information on the frequency and context of diversion and the use of nonprescribed and prescribed stimulant medications in adolescent and young adult populations. The purpose of this systematic review of the literature is to evaluate the extent and characteristics of stimulant misuse and diversion in attention-deficit/hyperactivity disorder (ADHD) and non-ADHD individuals. METHOD: We conducted a systematic review of the literature of available studies looking at misuse and diversion of prescription ADHD medications using misuse, diversion, stimulants, illicit use, and ADHD medications as key words for the search. RESULTS: We identified 21 studies representing 113,104 subjects. The studies reported rates of past year nonprescribed stimulant use to range from 5% to 9% in grade school- and high school-age children and 5% to 35% in college-age individuals. Lifetime rates of diversion ranged from 16% to 29% of students with stimulant prescriptions asked to give, sell, or trade their medications. Recent work suggests that whites, members of fraternities and sororities, individuals with lower grade point averages, use of immediate-release compared to extended-release preparations, and individuals who report ADHD symptoms are at highest risk for misusing and diverting stimulants. Reported reasons for use, misuse, and diversion of stimulants include to concentrate, improve alertness, 'get high,' or to experiment. CONCLUSIONS: The literature suggests that individuals both with and without ADHD misuse stimulant medications. Recent work has begun to document the context, motivation, and demographic profile of those most at risk for using, misusing, and diverting stimulants. The literature highlights the need to carefully monitor high-risk individuals for the use of nonprescribed stimulants and educate individuals with ADHD as to the pitfalls of the misuse and diversion of the stimulants
— id: 93597, year: 2008, vol: 47, page: 21, stat: Journal Article,

"Barriers to providing health services for HIV/AIDS, hepatitis C virus infection, and sexually transmitted infections in substance abuse treatment programs in the United States"
Bini, EJ; Kritz, S; Brown, LS; Robinson, J; Alderson, D; Rotrosen, J
2007 ;132(4):A468-A468, Gastroenterology
— id: 108203, year: 2007, vol: 132, page: A468, stat: Journal Article,

Health services for HIV/AIDS, HCV, and sexually transmitted infections in substance abuse treatment programs
Brown, Lawrence S Jr; Kritz, Steven; Goldsmith, R Jeffrey; Bini, Edmund J; Robinson, Jim; Alderson, Donald; Rotrosen, John
2007 Jul-Aug;122(4):441-451, Public health reports
The National Drug Abuse Treatment Clinical Trials Network conducted this study to determine the availability of and factors associated with infection-related health services in substance abuse treatment settings. In a cross-sectional descriptive design, state policies, reimbursement for providers, state level of priority, and treatment program characteristics were studied via written surveys of administrators of substance abuse treatment programs and of state health and substance abuse departments. Data from health departments and substance abuse agencies of 48 states and from 269 substance abuse treatment programs revealed that human immunodeficiency virus/acquired immunodeficiency syndrome-related services are more frequent than hepatitis C virus or sexually transmitted infection-related services, and that nonmedical services are more frequent than medical services. While the availability of infection-related health services is associated with medical staffing patterns, addiction pharmacotherapy services, and state priorities, reimbursement was the most significant determining factor. These findings suggest that greater funding of these health services in substance abuse treatment settings, facilitated by supportive state policies, represents an effective response to the excess morbidity and mortality of these substance use-related infections
— id: 95149, year: 2007, vol: 122, page: 441, stat: Journal Article,

A feasibility study of a web-based performance improvement system for substance abuse treatment providers
Forman, Robert; Crits-Christoph, Paul; Kaynak, Ovgu; Worley, Matt; Hantula, Donald A; Kulaga, Agatha; Rotrosen, John; Chu, Melissa; Gallop, Robert; Potter, Jennifer; Muchowski, Patrice; Brower, Kirk; Strobbe, Stephen; Magruder, Kathy; Chellis, A'Delle H; Clodfelter, Tad; Cawley, Margaret
2007 Dec;33(4):363-371, Journal of substance abuse treatment
We report here on the feasibility of implementing a semiautomated performance improvement system-Patient Feedback (PF)-that enables real-time monitoring of patient ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol use in outpatient substance abuse treatment clinics. The study was conducted in six clinics within the National Institute on Drug Abuse Clinical Trials Network. It involved a total of 39 clinicians and 6 clinic supervisors. Throughout the course of the study (consisting of five phases: training period [4 weeks], baseline [4 weeks], intervention [12 weeks], postintervention assessment [4 weeks], sustainability [1 year]), there was an overall collection rate of 75.5% of the clinic patient census. In general, the clinicians in these clinics had very positive treatment satisfaction and alliance ratings throughout the study. However, one clinic had worse drug use scores at baseline than other participating clinics and showed a decrease in self-reported drug use at postintervention. Although the implementation of the PF system proved to be feasible in actual clinical settings, further modifications of the PF system are needed to enhance any potential clinical usefulness
— id: 86623, year: 2007, vol: 33, page: 363, stat: Journal Article,

Relation of neurological soft signs to psychiatric symptoms in schizophrenia
Mittal, Vijay A; Hasenkamp, Wendy; Sanfilipo, Michael; Wieland, Susan; Angrist, Burton; Rotrosen, John; Duncan, Erica J
2007 Aug;94(1-3):37-44, Biological psychiatry
INTRODUCTION: Although several studies have identified abnormal rates of neurological soft signs (NSS) as a manifestation of CNS dysfunction in schizophrenia, differences in sample populations have contributed to a discrepancy in empirical findings. Furthermore, little is known about the potential of NSS to predict a clinical response to antipsychotic medications. The present study tests the associations between NSS and schizophrenia symptomatology and examines NSS as a potential marker for predicting treatment response. METHODS: Nineteen unmedicated male schizophrenia patients were treated prospectively with haloperidol for six weeks. The subjects were assessed for pre and post-treatment NSS and schizophrenia symptomatology (Brief Psychiatric Rating Scale, BPRS). RESULTS: NSS at baseline were significantly associated with baseline symptoms on the Positive, Negative, and Psychological Discomfort BPRS subscales. NSS showed a strong trend toward improvement during six weeks of a prospective haloperidol trial. Hierarchical linear regression analyses indicated that more severe baseline NSS predicted poorer response to haloperidol treatment as measured by post-treatment BPRS Total subscale scores. DISCUSSION: NSS at untreated baseline are associated with baseline symptom severity, and elevated NSS are predictive of a smaller degree of improvement in symptoms after antipsychotic treatment. These findings are consistent with the hypothesis that NSS are linked to the neuropathology that underlies schizophrenia symptomatology and course
— id: 106679, year: 2007, vol: 94, page: 37, stat: Journal Article,

Implementation of a smoking cessation treatment study at substance abuse rehabilitation programs: Smoking behavior and treatment feasibility across varied community-based outpatient programs
Reid, MS; Fallon, B; Sonne, S; Nunes, EV; Lima, J; Jiang, H; Tyson, C; Hiott, R; Arfken, C; Bohs, R; Orr, D; Muir, J; Pihlgren, E; Loree, A; Fuller, BE; Giordano, L; Robinson, J; Rotrosen, J
2007 SEP ;1(3):154-160, Journal of addiction medicine : JAM
Cigarette smoking is widely prevalent among individuals in treatment for drug or alcohol dependence; however, the treatment of nicotine addiction in this population has numerous obstacles at both programmatic and patient levels. Despite these difficulties, recent studies have demonstrated moderate success in implementing smoking cessation treatment in drug rehabilitation programs. The National Drug Abuse Treatment Clinical Trials Network sponsored a smoking cessation study in 13 community-based outpatient substance abuse rehabilitation programs across the country. The study evaluated the effectiveness of smoking cessation treatment provided as an adjunct to substance abuse treatment-as-usual. This report summarizes the practical and clinical experiences encountered at each of the study sites with regard to implementing the smoking cessation treatment intervention. Smoking behavior of the treatment clientele was assessed by anonymous survey at each site. In addition, sites were systematically characterized by using program review and assessment tools completed by the respective staff and program directors at the site. Survey and recruitment data indicated that cigarette smoking is more prevalent and that smoking cessation treatment is more feasible, in methadone maintenance treatment programs. Other factors associated with smoking behavior and with the recruitment of drug- and alcohol-dependent individuals into the smoking cessation treatment study are described
— id: 86970, year: 2007, vol: 1, page: 154, stat: Journal Article,

Characteristics of substance abuse treatment programs providing services for HIV/AIDS, hepatitis C virus infection, and sexually transmitted infections: the National Drug Abuse Treatment Clinical Trials Network
Brown, Lawrence S Jr; Kritz, Steven Allan; Goldsmith, R Jeffrey; Bini, Edmund J; Rotrosen, John; Baker, Sherryl; Robinson, Jim; McAuliffe, Patrick
2006 Jun;30(4):315-321, Journal of substance abuse treatment
Illicit drug users sustain the epidemics of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis C (HCV), and sexually transmitted infections (STIs). Substance abuse treatment programs present a major intervention point in stemming these epidemics. As a part of the 'Infections and Substance Abuse' study, established by the National Drug Abuse Treatment Clinical Trials Network, sponsored by National Institute on Drug Abuse, three surveys were developed; for treatment program administrators, for clinicians, and for state and District of Columbia health and substance abuse department administrators, capturing service availability, government mandates, funding, and other key elements related to the three infection groups. Treatment programs varied in corporate structure, source of revenue, patient census, and medical and non-medical staffing; medical services, counseling services, and staff education targeted HIV/AIDS more often than HCV or STIs. The results from this study have the potential to generate hypotheses for further health services research to inform public policy
— id: 68541, year: 2006, vol: 30, page: 315, stat: Journal Article,

Clarity of state guidance on infection-related health services in substance abuse treatment programs
Brown, LS; Kritz, SA; Rotrosen, J; Goldsmith, RJ; Bini, EJ; Robinson, J; Alderson, D
2006 ;31(4):S142-S142, Neuropsychopharmacology
— id: 108208, year: 2006, vol: 31, page: S142, stat: Journal Article,

Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials
Ciraulo, DA; Hitzemann, RJ; Somoza, E; Knapp, CM; Rotrosen, J; Sarid-Segal, O; Ciraulo, AM; Greenblatt, DJ; Chiang, CN
2006 FEB ;46(2):179-192, Journal of clinical pharmacology
In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest
— id: 62384, year: 2006, vol: 46, page: 179, stat: Journal Article,

Medication status affects the relationship of symptoms to prepulse inhibition of acoustic startle in schizophrenia
Duncan, Erica J; Bollini, Annie M; Lewison, Barbara; Keyes, Megan; Jovanovic, Tanja; Gaytan, Osvaldo; Egan, Glenn; Szilagyi, Sandor; Schwartz, Marion; Parwani, Arti; Chakravorty, Subhajit; Rotrosen, John
2006 Dec 7;145(2-3):137-145, Psychiatry research
Inhibition of the acoustic startle response by a smaller preliminary nonstartling stimulus is termed prepulse inhibition (PPI). Schizophrenia patients have impairments in PPI that may not fully normalize even when they are clinically stable on medication, particularly typical antipsychotics. There is evidence that more severe symptoms are associated with more severe PPI abnormalities, but the effect of antipsychotics on this relationship is not clear. Seventy-three male schizophrenia patients underwent acoustic startle and PPI testing. Symptom ratings were performed using the Brief Psychiatric Rating Scale (BPRS) and its subscales. Fifty-two subjects were treated with antipsychotic medication at time of testing; 21 were unmedicated. For all subjects, PPI was negatively correlated with the BPRS psychological discomfort subscale but not with BPRS total symptoms, BPRS positive symptoms or BPRS negative symptoms. For medicated subjects analyzed separately, there were no correlations with BPRS total scores or any subscales. For the unmedicated subjects analyzed separately, there were significant correlations of lower PPI with greater severity of BPRS total symptoms, positive symptoms and the psychological discomfort subscale. These data indicate that more severe symptoms are associated with lower PPI, but that medication status is an important factor in the relationship between symptom severity and sensorimotor gating
— id: 136559, year: 2006, vol: 145, page: 137, stat: Journal Article,

Diurnal variation in plasma homovanillic acid in patients with schizophrenia and healthy controls
Duncan, Erica; Bollini, Annie M; Sanfilipo, Michael; Wieland, Susan; Angrist, Burt; Cooper, Thomas B; Rotrosen, John
2006 Jan 31;81(2-3):323-326, Biological psychiatry
— id: 106680, year: 2006, vol: 81, page: 323, stat: Journal Article,

Reliability of low frequency reaction time oscillations in adult controls and preliminary data in patients with psychiatric and addictive disorders
Rotrosen, J; Debowy, D; Minerly, C; Di Martino, A; Castellanos, FX
2006 DEC ;31(2):S192-S192, Neuropsychopharmacology
— id: 70914, year: 2006, vol: 31, page: S192, stat: Journal Article,

Acute akathisia
Adler, Lenard A; Angrist, Burt; Rotrosen, John
Drug-induced movement disorders Malden, MA : Blackwell Futura, 2005,
— id: 5275, year: 2005, vol: , page: ?, stat: Chapter,

Nefazodone treatment of cocaine dependence with comorbid depressive symptoms
Ciraulo, Domenic A; Knapp, Clifford; Rotrosen, John; Sarid-Segal, Ofra; Ciraulo, Ann Marie; LoCastro, Joseph; Greenblatt, David J; Leiderman, Deborah
2005 ;100(Suppl1):23-31 Mar, Addiction
(from the journal abstract) Aims: In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5-HT-sub(2A) receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use. Design: An 8-week, double blind, placebo-controlled design was used. Setting: The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center. Participants: Subjects (n=69) met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher. Intervention: Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n=34) or matching placebo (n=35). All subjects received individual counseling. Measurements: Urinary measurements of benzoylecgonine (BE, three times per week) and self-reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning. Findings: Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self-reported cocaine use. Conclusions: These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels.
— id: 55774, year: 2005, vol: 100, page: 23, stat: Journal Article,

Nefazodone treatment of cocaine dependence with comorbid depressive symptoms
Ciraulo, Domenic A; Knapp, Clifford; Rotrosen, John; Sarid-Segal, Ofra; Ciraulo, Ann Marie; LoCastro, Joseph; Greenblatt, David J; Leiderman, Deborah
2005 Mar;100 Suppl 1:23-31, Addiction
AIMS: In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5-HT(2A) receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use. DESIGN: An 8-week, double blind, placebo-controlled design was used. SETTING: The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center. PARTICIPANTS: Subjects (n = 69) met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher. INTERVENTION: Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n = 34) or matching placebo (n = 35). All subjects received individual counseling. MEASUREMENTS: Urinary measurements of benzoylecgonine (BE, three times per week) and self-reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning. FINDINGS: Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self-reported cocaine use. CONCLUSIONS: These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels
— id: 140331, year: 2005, vol: 100 Suppl 1, page: 23, stat: Journal Article,

Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence
Elkashef, Ahmed; Holmes, Tyson H; Bloch, Daniel A; Shoptaw, Steve; Kampman, Kyle; Reid, Malcolm S; Somoza, Eugene; Ciraulo, Domenic; Rotrosen, John; Leiderman, Deborah; Montgomery, Ann; Vocci, Frank
2005 Mar;100 Suppl 1:91-101, Addiction
AIM: To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size. DESIGN: Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo. SETTING: Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University. PARTICIPANTS: The pooled data set consisted of 357 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized. INTERVENTION: All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy. MEASURES: Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group. FINDINGS: Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion. CONCLUSIONS: Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence
— id: 109291, year: 2005, vol: 100 Suppl 1, page: 91, stat: Journal Article,

A placebo controlled, double-blind study of mecamylamine treatment for cocaine dependence in patients enrolled in an opiate replacement program
Reid, Malcolm S; Angrist, Burt; Baker, Sherryl A; O'leary, Siobhan; Stone, Jennifer; Schwartz, Marion; Leiderman, Deborah; Montgomery, Ann; Elkashef, Ahmed; Majewska, Dorota; Robinson, James; Rotrosen, John
2005 Jun;26(2):5-14, Substance abuse
A placebo controlled, double-blind trial of mecamylamine treatment of cocaine dependence was performed in methadone or LAAM maintained subjects who met DSM-IV criteria for cocaine dependence. After an eight-week placebo run-in screening period, 35 subjects were randomly assigned to receive either mecamylamine (6 mg/day) or placebo transdermal patches for a 16-week treatment period. Outcome measures included quantitative urine benzoylecognine (BE) levels, self-report of cocaine use, cocaine craving, global impression scores, mood, retention, and safety. Mecamylamine was well tolerated, and study retention did not differ by treatment group. Evidence for cocaine use, based on urine BE levels and cocaine abstinence rates, did not differ by treatment group. Self reported cocaine use, cocaine craving, and global impression scores showed moderate improvement in both groups, with a significantly greater reduction in cocaine craving (p < 0.05) and self-rated severity of cocaine dependence (p < 0.05) in the placebo group. This pilot study does not support the effectiveness of mecamylamine for the treatment of cocaine dependence in methadone or LAAM maintained patients
— id: 74156, year: 2005, vol: 26, page: 5, stat: Journal Article,

A placebo-controlled screening trial of celecoxib for the treatment of cocaine dependence
Reid, Malcolm S; Angrist, Burt; Baker, Sherryl; Woo, Caroline; Schwartz, Marion; Montgomery, Ann; Majewska, Dorota; Robinson, James; Rotrosen, John
2005 Mar;100 Suppl 1:32-42, Addiction
AIMS: To conduct a medication screening trial study on the efficacy of celecoxib versus placebo for the treatment of cocaine dependence. DESIGN: A modified blinded, parallel group study in an outpatient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design. SETTING: The study was performed at the New York Medications Development Research Unit (MDRU). PARTICIPANTS: All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Twenty-three participants were enrolled in the treatment phase of the study. INTERVENTION: After a 2-week screening period, subjects were assigned randomly to receive either celebrex (200 mg/day) or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment. MEASUREMENTS: Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs and extrapyramidal side-effects tests. RESULTS: Study retention was similar across both treatment groups and safety measures indicated that celecoxib was moderately tolerated. Cocaine use, as measured by self-report and urine BE levels at end of treatment, indicated weaker improvement in the celecoxib group. Reductions in the intensity of cocaine craving were also weaker in the celecoxib group. Cocaine abstinence rates, global impression scores and all other related psychometric measures did not differ significantly between treatment groups. CONCLUSION: This study does not support the effectiveness of celecoxib for the treatment of cocaine dependence
— id: 56141, year: 2005, vol: 100 Suppl 1, page: 32, stat: Journal Article,

A placebo-controlled screening trial of olanzapine, valproate, and coenzyme Q10/L-carnitine for the treatment of cocaine dependence
Reid, Malcolm S; Casadonte, Paul; Baker, Sherryl; Sanfilipo, Michael; Braunstein, Dania; Hitzemann, Robert; Montgomery, Ann; Majewska, Dorota; Robinson, James; Rotrosen, John
2005 Mar;100 Suppl 1:43-57, Addiction
AIMS: To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L-carnitine combination versus placebo for the treatment of cocaine dependence. DESIGN: A four-arm, modified blinded, parallel group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design. SETTING: The study was performed at the New York Medications Development Research Unit (MDRU). PARTICIPANTS: All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Sixty-eight participants were enrolled with 39 completing the study. INTERVENTION: After a 2-week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day) combination or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment. MEASUREMENTS: Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side-effects tests. RESULTS: Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self-report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed. CONCLUSION: This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment of cocaine dependence
— id: 56140, year: 2005, vol: 100 Suppl 1, page: 43, stat: Journal Article,

Attention-deficit/hyperactivity disorder in adult patients with posttraumatic stress disorder (PTSD): is ADHD a vulnerability factor?
Adler, L A; Kunz, M; Chua, H C; Rotrosen, J; Resnick, S G
2004 Aug;8(1):11-16, Journal of attention disorders
OBJECTIVE: There is limited evidence suggesting a link between posttraumatic stress disorder (PTSD) and Attention-Deficit/ Hyperactivity Disorder (ADHD). This study examined the association between PTSD and ADHD using retrospective and current clinical evaluations. METHOD: Twenty-five male veterans with PTSD and 22 male veterans with panic disorder were evaluated for ADHD. The data was analyzed using chi-square and student's t-tests. RESULTS: Thirty-six percent of participants with PTSD and 9% of participants with panic disorder met criteria for childhood ADHD. Twenty-eight percent of participants with PTSD and 5% of participants with panic disorder met criteria for current ADHD. CONCLUSIONS: There appears to be a significant association of PTSD with ADHD. ADHD or common predisposing factors may increase the vulnerability for developing PTSD
— id: 48729, year: 2004, vol: 8, page: 11, stat: Journal Article,

Effects of D-cycloserine on negative symptoms in schizophrenia
Duncan, Erica J; Szilagyi, Sandor; Schwartz, Marion P; Bugarski-Kirola, Dragana; Kunzova, Alena; Negi, Shobhit; Stephanides, Myrsini; Efferen, Toby R; Angrist, Burt; Peselow, Eric; Corwin, June; Gonzenbach, Stephen; Rotrosen, John P
2004 Dec 1;71(2-3):239-248, Schizophrenia research
INTRODUCTION: The negative and cognitive symptoms of schizophrenia are poorly responsive to neuroleptic treatment. Glutamatergic dysfunction may mediate some of these symptoms. Low dose D-cycloserine (DCS) is a partial agonist at the glycine site of the NMDA-associated receptor complex, noncompetitively enhancing NMDA neurotransmission. Prior studies suggest a beneficial effect of DCS on negative symptoms and cognition. This treatment trial was initiated to confirm and extend these findings. METHODS: Twenty-two male schizophrenic subjects displaying prominent negative symptoms who were stabilized on typical neuroleptics completed the study. A randomized double-blind parallel group design was used to compare the effects of 50 mg p.o. QD of DCS to placebo over 4 weeks. The two subject groups did not differ significantly in age, age of onset of illness or time on current neuroleptic treatment. Symptoms were rated by means of the SANS, BPRS and Abrams and Taylor rating scale. Cognition was assessed with the Sternberg Memory Test and the Continuous Performance Test. RESULTS: Both medication groups improved over the 4 weeks of treatment. However, there were no significant differences between the DCS and placebo group on any symptom rating. DCS effects on cognition did not differ from placebo. DISCUSSION: This study did not detect improvement in negative symptoms or cognitive performance with DCS treatment that has been found in some prior studies. This negative finding may be attributed to small sample size, relatively short duration of treatment and the overall modest effect of DCS. Future studies of DCS should be adequately powered to detect a small to medium effect size and should provide for a longer treatment phase than was used in this study in order to avoid a type II error
— id: 94535, year: 2004, vol: 71, page: 239, stat: Journal Article,

Menstrual cycle phase effects on prepulse inhibition of acoustic startle
Jovanovic, Tanja; Szilagyi, Sandor; Chakravorty, Subhajit; Fiallos, Ana M; Lewison, Barbara J; Parwani, Arti; Schwartz, Marion P; Gonzenbach, Stephen; Rotrosen, John P; Duncan, Erica J
2004 May;41(3):401-406, Psychophysiology
Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating
— id: 94536, year: 2004, vol: 41, page: 401, stat: Journal Article,

Use of rivastigmine in patients with traumatic brain injury with cognitive deficits: A pilot study
Silver, JM; Rabinowitz, A; Koumaras, B; Chen, M; Potkin, SG; Arciniegas, DB; Reyes, PF; Warden, D; Harvey, PD; Rotrosen, J; Mirski, D
2004 DEC ;29(1):S237-S237, Neuropsychopharmacology
— id: 98182, year: 2004, vol: 29, page: S237, stat: Journal Article,

An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder
Somoza, Eugene C; Winhusen, Theresa M; Bridge, T Peter; Rotrosen, John P; Vanderburg, Douglas G; Harrer, Judy M; Mezinskis, Juris P; Montgomery, Margaret A; Ciraulo, Domenic A; Wulsin, Lawson R; Barrett, Jera A
2004 ;23(1):77-92, Journal of addictive diseases
A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted
— id: 94006, year: 2004, vol: 23, page: 77, stat: Journal Article,

Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia
Duncan, EJ; Szilagyi, S; Efferen, TR; Schwartz, MP; Parwani, A; Chakravorty, S; Madonick, SH; Kunzova, A; Harmon, JW; Angrist, B; Gonzenbach, S; Rotrosen, JP
2003 APR 15 ;53(8):184S-184S, Biological psychiatry
— id: 37114, year: 2003, vol: 53, page: 184S, stat: Journal Article,

Effects of D-cycloserine on negative symptoms in schizophrenia
Duncan, EJ; Szilagyi, S; Schwartz, M; Kunzova, A; Negi, S; Stephanides, M; Bugarski-Kirola, D; Efferen, TR; Peselow, E; Gonzenbach, S; Angrist, B; Rotrosen, JP
2003 APR 15 ;53(8):184S-184S, Biological psychiatry
— id: 37115, year: 2003, vol: 53, page: 184S, stat: Journal Article,

Effect of treatment status on prepulse inhibition of acoustic startle in schizophrenia
Duncan, Erica J; Szilagyi, Sandor; Efferen, Toby R; Schwartz, Marion P; Parwani, Arti; Chakravorty, Subhajit; Madonick, Steven H; Kunzova, Alena; Harmon, James W; Angrist, Burt; Gonzenbach, Stephen; Rotrosen, John P
2003 Apr;167(1):63-71, Psychopharmacology
RATIONALE: The acoustic startle response is inhibited when the startling stimulus is preceded by a weaker non-startling acoustic stimulus. This phenomenon, termed prepulse inhibition of acoustic startle (PPI), is impaired in schizophrenics compared to normal controls. To date, there is conflicting evidence regarding whether PPI impairments improve with antipsychotic treatment. OBJECTIVES: To examine the effect of medication status on PPI in schizophrenic subjects. METHODS: First, we performed acoustic startle testing on 16 schizophrenic subjects when they were acutely decompensated off medication and later after they were stabilized on antipsychotic treatment. Second, in a between-group design, we tested 21 schizophrenic subjects off medication, 16 subjects on atypical neuroleptics, and 27 subjects on typical neuroleptics. RESULTS: In both the test-retest study and the between-group study, ANOVAs revealed no significant changes in startle to pulse alone stimuli, habituation of startle to pulse alone stimuli, PPI, latency to response onset, or latency to response peak between the treatment conditions. CONCLUSIONS: Our results do not support the hypothesis that impaired sensorimotor gating in schizophrenia improves with antipsychotic treatment. Rather, impaired gating persists despite symptomatic improvement on medication
— id: 94537, year: 2003, vol: 167, page: 63, stat: Journal Article,

Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol
Duncan, Erica; Szilagyi, Sandor; Schwartz, Marion; Kunzova, Alena; Negi, Shobhit; Efferen, Toby; Peselow, Eric; Chakravorty, Subhajit; Stephanides, Myrsini; Harmon, James; Bugarski-Kirola, Dragana; Gonzenbach, Stephen; Rotrosen, John
2003 Aug 30;120(1):1-12, Psychiatry research
Studies of the acoustic startle response and of its inhibition by the presentation of a non-startling preliminary stimulus (prepulse inhibition, PPI) have revealed deficits in PPI in schizophrenic subjects compared to healthy controls. Animal studies indicate that atypical antipsychotics improve PPI deficits induced by NMDA antagonists more consistently than typical antipsychotics. The effect of medication status on PPI in schizophrenia is unresolved in the literature. In the current study the effects on PPI of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol were compared to the unmedicated state in subjects with schizophrenia. In a between-group design, 11 schizophrenic subjects on olanzapine, 16 subjects on haloperidol, and 14 subjects who were on no medication received acoustic startle testing with PPI determination. ANOVAs revealed no significant differences in startle to pulse alone stimuli, habituation of startle, or PPI between the olanzapine, haloperidol and unmedicated groups. These 41 subjects with schizophrenia were compared to a group of 21 historical healthy controls and found to have reduced PPI. These data do not indicate a preferential effect of olanzapine compared to haloperidol on sensorimotor gating in schizophrenia. The results are consistent with the hypothesis that PPI impairments are relatively stable across treatment conditions
— id: 106116, year: 2003, vol: 120, page: 1, stat: Journal Article,

Quantitative electroencephalographic studies of cue-induced cocaine craving
Reid, Malcolm S; Prichep, Leslie S; Ciplet, Debra; O'Leary, Siobhan; Tom, MeeLee; Howard, Bryant; Rotrosen, John; John, E Roy
2003 Jul;34(3):110-123, Clinical electroencephalography
Quantitative electroencephalographic (qEEG) profiles were studied in cocaine dependent patients in response to cocaine cue exposure. Using neurometric analytical methods, the spectral power of each primary bandwidth was computed and topographically mapped. Additional measures of cue-reactivity included cocaine craving, anxiety and related subjective ratings, and physiological measures of skin conductance, skin temperature, heart rate, and plasma cortisol and HVA levels. Twenty-four crack cocaine-dependent subjects were tested for their response to tactile, visual and audio cues related to crack cocaine or neutral items. All measures were analyzed for significant difference by comparing cocaine versus neutral cue conditions. An increase in cocaine craving, anxiety and related subjective ratings, elevated plasma cortisol levels, and a decrease in skin temperature, were induced by cocaine cue exposure. Distinct qEEG profiles were found during the paraphernalia handling and video viewing (eyes-open), and guided imagery (eyes-closed), phases of cocaine cue exposure. During paraphernalia handling and video viewing, there was an increase in beta activity accompanied by a drop in delta power in the frontal cortex, and an increase in beta mean frequency in the occipital cortex. In contrast, during guided imagery there was an increase in theta and delta power in the frontal cortex, and an increase in beta power in the occipital cortex. Correlation analyses revealed that cue-induced anxiety during paraphernalia handling and video viewing was associated with reduced high frequency and enhanced low frequency EEG activity. These findings demonstrated that EEG activation during cue-induced cocaine craving may be topographically mapped and subsequently analyzed for functional relevance
— id: 39049, year: 2003, vol: 34, page: 110, stat: Journal Article,

Measuring outcome in cocaine clinical trials: a comparison of sweat patches with urine toxicology and participant self-report
Winhusen, TM; Somoza, EC; Singal, B; Kim, S; Horn, PS; Rotrosen, J
2003 MAR ;98(3):317-324, Addiction
Aims To evaluate the advantages of using a sweat patch (PharmCheck(TM)) for detecting cocaine abuse in cocaine- dependent patients participating in a clinical trial: The utility of the sweat patch was assessed from the following perspectives: the reliability and validity of quantitative sweat patch results, the possible degradation of cocaine to benzoylecgonine (BE) as a function of the length of time that a patch is worn, the completeness of the dataset yielded by thrice-weekly urine toxicology compared with thrice-weekly and weekly sweat patches, and the relative costs associated with sweat patch versus urine measures. Design Data were collected during a 10-week out-patient clinical trial in which participants wore two sweat patches, one applied every visit and one applied weekly. Urine samples were collected thrice weekly, as were self-reports of substance use. Setting A multi- site clinical trial conducted in Boston, Cincinnati and New York, USA. Participants Twenty-seven participants with comorbid diagnoses of cocaine dependence and adult attention deficit disorder completed the study. Measurements Sweat patch and urine samples were analyzed by standard methods for cocaine and cocaine metabolites. Findings Quantitative sweat patch measures had good reliability in that the correlation between the weekly and per-visit patches was 0.96 (P < 0.0001). The concurrent validity, as judged by the correlation between quantitative urine BE levels and either weekly (0.76, P<0.0001) or per-visit (0.73, P<0.0001) cocaine sweat patch levels was reasonable. The correlation between the self-report of cocaine use and these same two patches, however, was lower (0.40, P < 0.05 and 0.30, P < 0.05, respectively). The results revealed no significant degradation of cocaine to BE associated with wearing the patch for a longer time. Finally, the per-visit patch provided cocaine use data on 80.5% of all study days (a total of 70), while urine toxicology and the weekly patch provided 77.4% and 76.1%, respectively. Conclusions The present findings suggest that the PharmCheck(TM) patch might be an attractive alternative to urine toxicology for use as an outcome measure in cocaine clinical trials
— id: 34089, year: 2003, vol: 98, page: 317, stat: Journal Article,

Inferior frontal white matter anisotropy and negative symptoms of schizophrenia: a diffusion tensor imaging study
Wolkin, Adam; Choi, Steven J; Szilagyi, Sandor; Sanfilipo, Michael; Rotrosen, John P; Lim, Kelvin O
2003 Mar;160(3):572-574, American journal of psychiatry
OBJECTIVE: The purpose of this study was test the hypothesis that abnormalities of inferior frontal white matter are related to the negative symptoms of schizophrenia. METHOD: Fractional anisotropy of white matter tracts in the prefrontal area of 10 schizophrenic patients was determined by diffusion tensor imaging. Patients were also assessed for severity of negative symptoms by using the Schedule for the Assessment of Negative Symptoms (SANS). RESULTS: Inferior frontal white matter fractional anisotropy was significantly inversely correlated with the SANS global ratings of negative symptoms. CONCLUSIONS: These data, while preliminary, suggest that impaired white matter integrity in the inferior frontal region may be associated with the severity of negative symptoms in schizophrenia
— id: 94337, year: 2003, vol: 160, page: 572, stat: Journal Article,

Reduced frontal white matter integrity in cocaine dependence: a controlled diffusion tensor imaging study
Lim, Kelvin O; Choi, Steven J; Pomara, Nunzio; Wolkin, Adam; Rotrosen, John P
2002 Jun 1;51(11):890-895, Biological psychiatry
BACKGROUND: In vivo magnetic resonance studies have found that cocaine dependence is associated with T2 signal hyperintensities and metabolite abnormalities in cerebral white matter (WM). Functional neuroimaging studies have suggested that chronic cocaine use is primarily associated with frontal lobe deficits in regional cerebral blood flow and brain glucose metabolism levels; however, the effects of cocaine dependence, if any, on frontal WM microstructure are unknown. Thus, we sought to examine the effects of cocaine dependence on frontal WM integrity. METHODS: Diffusion tensor imaging was employed to examine the WM integrity of frontal regions at four levels: 10 mm above, 5 mm above, 0 mm above, and 5 mm below the anterior commissure-posterior commissure (AC-PC) plane. The fractional anisotropy (FA) of 12 cocaine-dependent patients and 13 age-similar control subjects was compared. RESULTS: The cocaine-dependent patients had significantly reduced FA in the frontal WM at the AC-PC plane and a trend toward reduced FA at 5 mm below the AC-PC plane, suggestive of reduced WM integrity in these regions. CONCLUSIONS: These findings were consistent with the hypothesis that cocaine dependence involves alterations in orbitofrontal connectivity, which may be involved in the decision-making deficits seen in this disorder
— id: 32117, year: 2002, vol: 51, page: 890, stat: Journal Article,

Treatment predictors of extrapyramidal side effects in patients with tardive dyskinesia: results from Veterans Affairs Cooperative Study 394
Lohr, James B; Caligiuri, Michael P; Edson, Robert; Lavori, Philip; Adler, Lenard A; Rotrosen, John; Hitzemann, Robert
2002 Apr;22(2):196-200, Journal of clinical psychopharmacology
Predictors for the development of tardive dyskinesia (TD) have been studied extensively over the years, yet there are few studies of predictors of the course of TD after it has developed. Moreover, few studies have examined predictors of the course of other extrapyramidal side effects (EPS) in patients maintained on neuroleptics. The purpose of this study was to determine which modifiable variables are important in the prediction of EPS in patients with persistent TD over a period of as long as 2 years. One hundred fifty-eight patients enrolled in the Veterans Affairs Cooperative Study 394 were included in this study. A linear mixed-effects (LME) analysis to estimate the Abnormal Involuntary Movement Scale score (for TD severity), Simpson-Angus Scale (for parkinsonism severity), and Barnes Akathisia Scale at any given time after intake assessment was performed. The severity of each of the TD and EPS outcomes at any given visit was predicted by their respective baseline severity scores. Additional predictors of a favorable course of TD included lower doses of antipsychotic medications and use of anticholinergic medications. Other predictors of a favorable course of EPS included younger age and the use of atypical antipsychotic medication (for rigidity) and the use of anticholinergic medication (for tremor). These findings indicate that clinician-modifiable factors related to medication usage can influence the outcome of TD and EPS in patients with persistent TD
— id: 66502, year: 2002, vol: 22, page: 196, stat: Journal Article,

Cognitive performance in schizophrenia: relationship to regional brain volumes and psychiatric symptoms
Sanfilipo, Michael; Lafargue, Todd; Rusinek, Henry; Arena, Luigi; Loneragan, Celia; Lautin, Andrew; Rotrosen, John; Wolkin, Adam
2002 Nov 30;116(1-2):1-23, Psychiatry research
In an all-male sample of schizophrenic patients stabilized by medication (n=62) and normal controls (n=27), we obtained neuropsychological test data and high-resolution whole brain magnetic resonance scans, as well as detailed psychiatric rating scales on a subset of the patients (n=47). Schizophrenic patients had significantly worse overall age-adjusted cognitive performance than normal controls (average z-score=-0.90, range=-0.60 to -1.81), which included relatively more severe deficits with different types of memory, psychomotor speed, verbal fluency and verbal abstraction. Schizophrenic patients also had significantly smaller bilateral volumes in gray but not white matter in the prefrontal region, superior temporal gyrus and whole temporal lobe, but no group differences were observed in the hippocampus and parahippocampus. Correlations between the brain regions and cognitive performance revealed different sets of significant relationships for the two groups, particularly in the prefrontal and hippocampal regions. In addition, inverse correlations were observed between certain cognitive abilities (psychomotor speed, cognitive flexibility and verbal fluency) and patients' psychiatric ratings, especially with measures of negative symptoms. The convergence of findings for schizophrenic patients regarding the prefrontal region, negative symptoms, psychomotor speed and cognitive flexibility suggests that schizophrenic negative symptoms may involve disruption of frontal-subcortical connections
— id: 73261, year: 2002, vol: 116, page: 1, stat: Journal Article,

Differential effects of dopamine antagonists on locomotor activity, conditioned activity and conditioned place preference induced by cocaine in rats
Adams JU; Careri JM; Efferen TR; Rotrosen J
2001 Dec;12(8):603-611, Behavioural pharmacology
Neuronal substrates that mediate the conditioned effects of cocaine have not been well characterized. To examine dopaminergic mechanisms, three antagonists were tested for their capacity to inhibit the expression of conditioned locomotor activity and conditioned place preference in rats. Antagonists were also assessed against acute cocaine-stimulated locomotor activity for comparison. For locomotor activity conditioning, six conditioning sessions were conducted over a 10-day period. Paired rats received 10 mg/kg cocaine prior to activity sessions and saline after; unpaired controls received saline prior and cocaine after. For place preference conditioning, eight conditioning sessions were conducted over a 13-day period; rats received 10 mg/kg cocaine while restricted to one of two distinct chambers and, on alternate days, they received saline in the other. Antagonists (haloperidol, raclopride and SCH23390; 0.03-0.1 mg/kg) were given only on test days for conditioned effects. All three antagonists significantly and dose-dependently attenuated the direct stimulatory effect of cocaine. SCH23390 showed a tendency to reduce the expression of conditioned locomotor activity, and only haloperidol blocked the expression of conditioned place preference. Thus, direct and conditioned stimulant effects of cocaine were shown to be differentially sensitive to dopamine receptor blockade. Further, conditioned stimulant effects differed from conditioned reinforcing effects in this regard
— id: 39458, year: 2001, vol: 12, page: 603, stat: Journal Article,

Prepulse inhibition of the acoustic startle response in cocaine-withdrawn rats
Adams JU; Efferen TR; Duncan EJ; Rotrosen J
2001 Apr;68(4):753-759, Pharmacology biochemistry & behavior
Prepulse inhibition (PPI) of startle is a sensorimotor gating task in which a low-intensity acoustic stimulus presented prior to a high-intensity, startle-eliciting stimulus can attenuate the acoustic startle response (ASR). Previous studies on startle reactivity in cocaine-withdrawn rats have found minimal changes; the present study extends this work to the gating of ASR. In Experiment 1, rats were injected daily with either saline or cocaine (30 mg/kg i.p.) for 2 weeks. ASR and PPI were measured prior to, and at 3- and 14-day withdrawal from, the chronic treatment. No effect of cocaine treatment was found on either measure. In Experiment 2, treatment was extended to 8 weeks, and an earlier withdrawal time point (1 day) was added. Rats treated with cocaine for 8 weeks exhibited lower startle reactivity during withdrawal compared with saline-treated controls. PPI did not differ between treatment groups. Thus, extended chronic treatment with cocaine rendered significant effects on startle responsivity. Further, this finding mirrors the blunted ASR exhibited in chronic cocaine users [Neuropsychopharmacology 22 (2000) 89.]
— id: 23554, year: 2001, vol: 68, page: 753, stat: Journal Article,

Commentary on: "Differential effects of amphetamine and neuroleptics on negative vs. positive symptoms in schizophrenia." Psychopharmacology (1980) 72:17-19
Angrist, B; Rotrosen, J; Gershon, S
2001 Nov;158(3):219-221, Psychopharmacology
— id: 106681, year: 2001, vol: 158, page: 219, stat: Journal Article,

Effects of smoking on acoustic startle and prepulse inhibition in humans
Duncan E; Madonick S; Chakravorty S; Parwani A; Szilagyi S; Efferen T; Gonzenbach S; Angrist B; Rotrosen J
2001 Jul;156(2-3):266-272, Psychopharmacology
RATIONALE: Prepulse inhibition of the acoustic startle response (PPI) is a paradigm in which a startle response to an auditory stimulus is reduced when that stimulus is preceded by a lower intensity, non-startling stimulus (prepulse). PPI is used as an operational measure of sensorimotor gating in both humans and other mammals. Acute administration of nicotine enhances PPI in rats, an effect that has been recently demonstrated in humans. OBJECTIVES: We compared PPI in 12 male smokers and 14 male non-smokers tested in four repeat startle sessions across 2 test days in order to examine further the effects of smoking and smoking withdrawal on acoustic startle and PPI. METHODS: In a crossover design, the smokers smoked ad lib or abstained from smoking overnight prior to 9 a.m. testing. These 2 test days were in randomized order. On both days, smokers were immediately retested after smoking three cigarettes. Non-smokers were tested twice on each of 2 separate days. RESULTS: Across sessions, the smokers had reduced startle to pulse alone stimuli in the first block of each session when compared to the non-smokers. The non-smokers had no change in gating across their four test sessions. For the smokers, the abstinence condition produced a non-significant reduction in PPI compared to that of the ad lib smoking day. During the smoking abstinence session, smokers had comparable gating to non-smokers. Smoking immediately after washout produced a significant improvement in PPI such that gating in the smokers exceeded that of the non-smokers. CONCLUSION: Smoking after overnight washout from cigarettes enhanced sensorimotor gating compared to pre-smoking values and compared to gating in non-smokers
— id: 23573, year: 2001, vol: 156, page: 266, stat: Journal Article,

Clinical and sensorimotor gating effects of ketamine in normals
Duncan EJ; Madonick SH; Parwani A; Angrist B; Rajan R; Chakravorty S; Efferen TR; Szilagyi S; Stephanides M; Chappell PB; Gonzenbach S; Ko GN; Rotrosen JP
2001 Jul;25(1):72-83, Neuropsychopharmacology
The clinical similarities between PCP psychosis and schizophrenia have contributed importantly to the development of the glutamate hypothesis of schizophrenia. Sensory gating, as measured by prepulse inhibition of the acoustic startle reflex (PPI), is impaired in patients with schizophrenia. In animals, the noncompetitive NMDA antagonists PCP and ketamine disrupt PPI in a way that resembles the defect seen in schizophrenia. The purpose of this work is to investigate the modulation of sensory gating in humans by subanaesthetic doses of ketamine. 16 healthy male subjects received a 60-min infusion of ketamine (0.5 mg/kg) or normal saline on two separate days in a randomized double-blind crossover design. Clinical ratings and PPI were done during the infusion on both days. Ketamine produced robust clinical effects. Dissociative symptoms as measured by the CADSS increased from 0 +/- 0.0 to 29.3 +/- 14.3; negative symptoms (Affect Rating Scale) increased from 17.2 +/- 0.8 to 24.8 +/- 3.1; and total BPRS scores increased from 18.3 +/- 0.8 to 26.4 +/- 5.1. ANOVAs for these ratings were all significant at the p <.000 level, although BPRS increases were not in the range seen in decompensated schizophrenic patients. The amplitudes of the startle responses to pulse-alone stimuli were not significantly different on ketamine and placebo days. Ketamine did not cause disruption in PPI as expected. On the contrary, in the first block of the PPI session ketamine significantly enhanced PPI (ANOVA; F=6.15, p =.026). These results indicate that the clinical effects of ketamine are not coupled with schizophrenic-like disruption of PPI in normal controls
— id: 20471, year: 2001, vol: 25, page: 72, stat: Journal Article,

Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain
Fowler JS; Volkow ND; Logan J; Franceschi D; Wang GJ; MacGregor R; Shea C; Garza V; Pappas N; Carter P; Netusil N; Bridge P; Liederman D; Elkashef A; Rotrosen J; Hitzemann R
2001 May 4;68(24):2759-2768, Life sciences
In this study, we investigated whether treatment with L-deprenyl, a selective monoamine oxidase B (MAO B) inhibitor, also inhibits MAO A or the dopamine transporter in the human brain. Six normal volunteers (age 46+/-6 yrs) had two PET sessions, one at baseline and one following L-deprenyl (10 mg/day) for 1 week. Each session included one scan with [11C]clorgyline (to assess MAO A) and one scan 2 hours later with [11C]cocaine (to assess dopamine transporter availability). A 3-compartment model was used to compare the plasma-to-brain transfer constant, K1 (a function of blood flow) and lambdak3 (a kinetic term proportional to brain MAO A) before and after treatment. Dopamine transporter availability was measured as the ratio of distribution volumes of the striatum to cerebellum (DVR) which is equal to Bmax/KD +1. L-Deprenyl treatment for 1 week did not affect either brain MAO A activity or dopamine transporter availability. There was a non-significant trend for an increase in K1 after L-deprenyl. These results confirm that L-deprenyl after one week of treatment at doses typically used clinically is selective for MAO B and that it does not produce a measurable affect on the dopamine transporter, suggesting that MAO A inhibition and dopamine transporter blockade do not contribute to its pharmacological effects
— id: 23574, year: 2001, vol: 68, page: 2759, stat: Journal Article,

Conditioned locomotor stimulant effects of cocaine in rats do not result from interference with habituation
Adams JU; Careri JM; Efferen TR; Rotrosen J
2000 Jul;151(1):13-18, Psychopharmacology
RATIONALE: Classical conditioning has been proposed to account for the hyperactivity observed in drug-free rats when placed in an environment previously paired with cocaine administration. However, an alternative explanation is that hyperactivity results from an inability of rats to habituate to the environment under the influence of cocaine. OBJECTIVES: In this study, preconditioning exposure to the test environment was increased from one session (standard procedure) to seven (modified procedure) to test the 'antihabituation' hypothesis. METHODS: After preconditioning exposure, six conditioning sessions took place over a 10-day to 13-day period. Paired rats received 10 mg/kg cocaine i.p. prior to activity sessions and saline i.p. upon return to the colony room. Unpaired rats received saline prior to and cocaine after activity sessions. Time-off rats were withheld from the activity boxes, but were subject to all other procedures during conditioning. On the test day, all rats received saline prior to activity sessions. RESULTS: In the standard procedure, paired rats exhibited significantly greater activity than unpaired rats on the test day, consistent with previous reports. In the modified procedure, mean activity (all rats) decreased between the first and last preconditioning sessions. Still, the paired group exhibited greater activity than the unpaired group on the test day, suggesting that a conditioned stimulant effect developed in habituated rats. Activity in the time-off group did not significantly differ from the unpaired group demonstrating the habituation had not dissipated over this time period. CONCLUSIONS: These results support the conclusion that hyperactivity observed on the test day was not a result of antihabituation effects of cocaine
— id: 23555, year: 2000, vol: 151, page: 13, stat: Journal Article,

Diminished acoustic startle in chronic cocaine users
Efferen TR; Duncan EJ; Szilagyi S; Chakravorty S; Adams JU; Gonzenbach S; Angrist B; Butler PD; Rotrosen J
2000 Jan;22(1):89-96, Neuropsychopharmacology
— id: 8600, year: 2000, vol: 22, page: 89, stat: Journal Article,

Impaired prepulse inhibition of acoustic startle in schizophrenia
Parwani A; Duncan EJ; Bartlett E; Madonick SH; Efferen TR; Rajan R; Sanfilipo M; Chappell PB; Chakravorty S; Gonzenbach S; Ko GN; Rotrosen JP
2000 Apr 1;47(7):662-669, Biological psychiatry
BACKGROUND: Schizophrenics show deficits in sensorimotor gating, as measured by prepulse inhibition of acoustic startle (PPI). The goal of this investigation is to further characterize PPI and habituation deficits in schizophrenia, and to examine whether differing subgroups of schizophrenics would show comparable PPI deficits. METHODS: PPI was measured in 24 male schizophrenic subjects (9 acutely decompensated inpatients and 15 stable outpatients) and in 20 age-matched normal control subjects. Schizophrenic subjects were rated for positive and negative symptoms at the time of testing. RESULTS: Schizophrenic subjects showed deficits in prepulse inhibition and habituation as compared to normal subjects. Similar latency facilitation was produced by the prepulse in both groups. Acutely decompensated inpatients and stable outpatients did not differ in percent PPI. PPI did not correlate with severity of positive or negative symptoms. CONCLUSIONS: These results suggest that schizophrenic subjects have impaired central inhibitory mechanisms as measured by PPI, and support the hypothesis that periods of relative clinical remission are not accompanied by normalization of sensorimotor gating
— id: 20472, year: 2000, vol: 47, page: 662, stat: Journal Article,

Fine volumetric analysis of the cerebral ventricular system in schizophrenia: further evidence for multifocal mild to moderate enlargement
Sanfilipo M; Lafargue T; Arena L; Rusinek H; Kushner K; Lautin A; Loneragan C; Vaid G; Rotrosen J; Wolkin A
2000 ;26(1):201-216, Schizophrenia bulletin
We used traditional volumetric regional analysis and a finer anterior-posterior (AP) profile volumetric analysis to examine the cerebral ventricular system in an all-male, demographically matched sample of schizophrenia patients (n = 73) and normal controls (n = 29) using 2.8-mm-thin coronal T1-weighted magnetic resonance images from a 1.5 tesla scanner. Traditional regional analysis was performed on various regions using absolute volumes after adjusting for intracranial volume (ICV) and age. The fine AP profile analysis was done by intrasubject 'stacking' of contiguous coronal cross-sectional volumes (adjusted for ICV and age) across the AP plane, intersubject AP alignment of all slices relative to the mammillary bodies, and plotting of slice volumes along the AP plane with 95 percent t-test-based confidence intervals. Schizophrenia subjects had mild to moderate multifocal ventricular enlargement (overall effect size d = 0.48), which was especially prominent in the right posterior temporal horn and, more generally, in the central to posterior portions of the lateral and third ventricles. Schizophrenia subjects also had milder enlargement in the left frontal horn, but no significant differences were found in the anterior temporal horns and the right frontal horn. Post hoc analyses of demographic, clinical, and neuropsychological variables did not account for much variance in the ventriculomegaly observed in the schizophrenia group. The lack of a single locus in the observed ventricular enlargement, the nonsignificant results from schizophrenia subtypes based on regional distributions, and the strong positive correlations among the ventricular regions for the schizophrenia group suggest that the ventriculomegaly seen in this chronic population reflects a single brainwide disease process leading to a multifocal or patchy loss of integrity in brain structure
— id: 23575, year: 2000, vol: 26, page: 201, stat: Journal Article,

Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms
Sanfilipo M; Lafargue T; Rusinek H; Arena L; Loneragan C; Lautin A; Feiner D; Rotrosen J; Wolkin A
2000 May;57(5):471-480, Archives of general psychiatry
BACKGROUND: Previous research has provided evidence for brain abnormalities in schizophrenia, but their relationship to specific clinical symptoms and syndromes remains unclear. METHODS: With an all-male demographically similar sample of 53 schizophrenic patients and 29 normal control subjects, cerebral gray and white matter volumes (adjusted for intracranial volume and age were determined for regions in the prefrontal lobe and in the superficial and mesial temporal lobe using T1-weighted magnetic resonance imaging with 2.8-mm coronal slices. RESULTS: As a group, schizophrenic patients had wide-spread bilateral decrements in gray matter in the pre-frontal (7.4%) and temporal lobe regions (8.9%), but not in white matter in these regions. In the temporal lobe, gray matter reductions were found bilaterally in the superior temporal gyrus (6.0%), but not in the hippocampus and parahippocampus. While there were no overall group differences in white matter volumes, widespread decrements in prefrontal white matter in schizophrenic patients (n = 53) were related to higher levels of negative symptoms (partial r[49] = -0.42, P = .002), as measured by the Scale for the Assessment of Negative Symptoms. A post hoc analysis revealed that schizophrenic patients with high negative symptoms had generalized prefrontal white matter reductions (11.4%) that were most severe in the orbitofrontal subregion (15.1%). CONCLUSIONS: These results suggest that gray matter deficits may be a fairly common structural abnormality of schizophrenia, whereas reductions in prefrontal white matter may be associated with schizophrenic negative symptoms
— id: 23576, year: 2000, vol: 57, page: 471, stat: Journal Article,

Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study #394 Study Group
Adler, L A; Rotrosen, J; Edson, R; Lavori, P; Lohr, J; Hitzemann, R; Raisch, D; Caligiuri, M; Tracy, K
1999 Sep;56(9):836-841, Archives of general psychiatry
BACKGROUND: Several short-term, controlled trials have documented the efficacy of vitamin E in treating tardive dyskinesia. However, the persistent nature of the disease prompted us to perform a multicenter, longer-term trial of vitamin E. METHODS: The study was a prospective, randomized, 9-site trial of up to 2 years of treatment with d-vitamin E (1600 IU/d) vs matching placebo. One hundred fifty-eight subjects with tardive dyskinesia who were receiving neuroleptic medications were enrolled. The blinded assessments performed were clinical (Abnormal Involuntary Movements Scale, Barnes Akathisia Scale, and Modified Simpson-Angus [for Extrapyramidal Symptoms] Scale) and electromechanical assessments of movement disorders, psychiatric status (Brief Psychiatric Rating Scale), and functioning (Global Assessment of Functioning). There were no significant differences in baseline demographic characteristics or in study assessments between the group that received vitamin E and the group that received placebo. RESULTS: Vitamin E was well tolerated and subject compliance with medication was good and similar between treatment groups. One hundred seven subjects (70% of those receiving vitamin E and 66% of subjects receiving placebo) completed at least 1 year of treatment. There were no significant effects of vitamin E on total scores or subscale scores for the AIMS, electromechanical measures of dyskinesia, or scores from the other 4 scales. CONCLUSION: This long-term, randomized trial of vitamin E vs placebo found no evidence for efficacy of vitamin E in the treatment of tardive dyskinesia
— id: 132303, year: 1999, vol: 56, page: 836, stat: Journal Article,

Vitamin E in the treatment of
Adler, LA; Edson, R; Rotrosen, J; Lavori, P; Tracy, K; Lohr, J; Hitzemann, R; Caligiuri, M; Raisch, D
1999 APR 15 ;45(8S):108S-108S, Biological psychiatry
— id: 54035, year: 1999, vol: 45, page: 108S, stat: Journal Article,

Long-term treatment effects of vitamin E for tardive dyskinesia
Adler LA; Edson R; Lavori P; Peselow E; Duncan E; Rosenthal M; Rotrosen J
1998 Jun 15;43(12):868-872, Biological psychiatry
BACKGROUND: Several studies have found that alpha-tocopherol (vitamin E) can effectively treat tardive dyskinesia (TD). A limitation of these trials is their short treatment durations (maximum of 12 weeks), which do not allow us to address the effects of long-term treatment. METHODS: To participate, patients had to have TD and be on stable oral medications. The study enrolled 40 patients who received up to 36 weeks of treatment with d-vitamin E (1600 IU per day) or placebo. RESULTS: Using the Abnormal Involuntary Movements Scale (AIMS) score (sum of items #1-7) to measure TD severity, the study found a significant difference (3 points) in mean AIMS scores, in favor of vitamin E, starting at 10 weeks of treatment and continuing through the full 36 weeks. We used linear mixed-effects regression to quantify the impact of several covariates, and found that treatment assignment. TD duration, and chlorpromazine equivalents had significant effects on decreasing the AIMS score. CONCLUSIONS: The study's finding that vitamin E is effective in treating TD agrees with results from prior studies and provides evidence that the effect may extend to treatment of up to 36 weeks. These findings are in direct contrast to those of VA Cooperative Study #394, a much larger, long-term, multi-site study, conducted by many of the same investigators, in which Vitamin E was not superior to placebo
— id: 23578, year: 1998, vol: 43, page: 868, stat: Journal Article,

Structural magnetic resonance image averaging in schizophrenia
Wolkin A; Rusinek H; Vaid G; Arena L; Lafargue T; Sanfilipo M; Loneragan C; Lautin A; Rotrosen J
1998 Aug;155(8):1064-1073, American journal of psychiatry
OBJECTIVE: Intersubject averaging of structural magnetic resonance (MR) images has been infrequently used as a means to study group differences in cerebral structure throughout the brain. In the present study, the authors used linear intersubject averaging of structural MR images to evaluate the validity and utility of this technique and to extend previous research, conducted using a different approach to image averaging, in which reduction in thalamic size and abnormalities in perithalamic white matter tracts in the brains of schizophrenic patients were reported by Andreasen et al. METHOD: A 1.5-T MR scanner was used to obtain high-resolution, whole brain T1-weighted structural MR images for an age-matched sample of 25 schizophrenic patients and 25 normal control subjects. A 'bounding box' procedure was used to create a single 'averaged' brain for the schizophrenic group and for the control group. Differences in signal intensity between the two average brains were examined on a pixel-wise basis through use of one-tailed effect size maps. RESULTS: Effect size maps revealed widespread patchy signal intensity differences between the two groups in both cortical and periventricular areas, including major white matter tracts. The signal intensity differences were consistent with cortical thinning/sulcal widening and ventricular enlargement. No differences were found within thalamus or in immediately surrounding white matter. Effect size maps for differences (schizophrenic minus normal subjects) had only small values. CONCLUSIONS: These results are consistent with diffuse structural brain abnormalities of both gray and white matter in schizophrenic populations such as the one in this study
— id: 23577, year: 1998, vol: 155, page: 1064, stat: Journal Article,

Reliability of an instrumental assessment of tardive dyskinesia: results from VA Cooperative Study #394
Caligiuri MP; Lohr JB; Rotrosen J; Adler L; Lavori P; Edson R; Tracy K
1997 Jul;132(1):61-66, Psychopharmacology
Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant treatment for tardive dyskinesia (TD) conducted by the Department of Veteran Affairs Cooperative Studies Program. One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia. Dyskinetic hand movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient. In the present report, we describe the training procedures and results of a multi-center reliability assessment of this procedure. Data from nine study centers comprising 45 individual patients with six trials each (three from left hand and three from right hand) were reanalyzed by an independent investigator and the results were subjected to reliability assessment. For the statistic of interest (average coefficient of variation over trials 2 and 3 for each hand, then take the larger of these two values), we found very high intraclass correlation coefficients for reliability over all patients across sites (ICC = 0.995). We also calculated the reliability of the measures across trials within patient for each combination of hand (right, left, dominant), rater group (site, control), and trials set (all three, trials 2 and 3). For a given hand and trial set, the reliability of the site raters was similar to that of the control. This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training
— id: 23579, year: 1997, vol: 132, page: 61, stat: Journal Article,

Interrater reliability issues in multicenter trials, Part II: Statistical procedures used in Department of Veterans Affairs Cooperative Study #394
Edson R; Lavori P; Tracy K; Adler LA; Rotrosen J
1997 ;33(1):59-67, Psychopharmacology bulletin
The primary goal of Veterans Affairs (VA) Cooperative Study (CS) #394 is to determine if vitamin E is a safe and efficacious treatment for tardive dyskinesia (TD). The study uses various instruments to assess subjects for movement disorders (Abnormal Involuntary Movement Scale [AIMS], and Barnes Akathisia Scale [BAS]), psychopathology (Anchored Brief Psychiatric Rating Scale [BPRS]), and level of functioning (Global Assessment of Functioning scale [GAF]). Since the study involves nine sites, each with its own set of raters, it is important to establish and maintain high interrater reliability (IRR) on these instruments throughout the study and to identify raters who differ significantly from the others. To make this determination, personnel at each site assessed subjects from standardized videotapes on the AIMS, BAS, and Anchored BPRS, and rated written vignettes on the GAF. We fit these data to a two-way additive model to identify nonstandardized raters (i.e., those whose average ratings were significantly lower or higher than the others, or those whose scores, after adjusting for subject and rater effects, were highly variable). The proportion of nonstandardized raters ranged from 7 percent (Anchored BPRS) to 33 percent (AIMS). The estimated intraclass correlation coefficients (ICCs) indicated moderate reliability for the AIMS, BAS, and Anchored BPRS (0.73 to 0.75) and excellent agreement for the GAF (0.90). The companion article (Part I: Tracy et al. 1997, page 53 of this issue) describes the procedures used to train the raters for this study
— id: 23580, year: 1997, vol: 33, page: 59, stat: Journal Article,

Interrater reliability issues in multicenter trials, Part I: Theoretical concepts and operational procedures used in Department of Veterans Affairs Cooperative Study #394
Tracy K; Adler LA; Rotrosen J; Edson R; Lavori P
1997 ;33(1):53-57, Psychopharmacology bulletin
This article describes a standardized method for establishing and maintaining desired levels of interrater reliability (IRR) in multicenter trials. The procedure involves six steps: distribution of procedural guides, distribution of an introduction tape, initial distribution of patient interviews to rate, training at the study kickoff meeting, ongoing IRR monitoring, and group training throughout the study. This method is being used in a national Veterans Affairs Cooperative Study (CS #394), involving nine sites to examine the treatment effects of vitamin E on tardive dyskinesia. The six-step standardized process allowed for early detection of areas of concern in assessment administration. When comparing intraclass correlation coefficients (ICCs) at different points in the initial training, the Barnes Akathisia Scale and Anchored Brief Psychiatric Rating Scale reliability improved from 0.68 to 0.74 and from 0.54 to 0.87, respectively. After analyzing the ratings collected prior to the start of CS #394, data were collected to conduct the first check on Abnormal Involuntary Movement Scale (AIMS) IRR during enrollment; the estimated ICC for the AIMS had decreased from 0.87 to 0.60. Raters were instructed to re-assess the subjects from the first videotape on the AIMS and received additional training. The re-rating indicated very good reliability, 0.84, IRR was measured once for the Global Assessment of Functioning Scale resulting in an ICC of 0.90. The companion article (Part II: Edson et al. 1997, page 59 of this issue) describes the statistical procedures used to measure IRR
— id: 12411, year: 1997, vol: 33, page: 53, stat: Journal Article,

Co-morbidity of attention deficit disorder in adult patients screened for
Adler, LA; Resnick, S; Rotrosen, J
1996 APR 1 ;39(7):185-185, Biological psychiatry
— id: 52981, year: 1996, vol: 39, page: 185, stat: Journal Article,

Prescribing characteristics of newer generation antidepressants in a veterans affairs psychiatry clinic
Adler, LA; Vanderburg, D; Resnick, S; Rotrosen, J
1996 NOV ;32(3):406-406, Psychopharmacology bulletin
— id: 52725, year: 1996, vol: 32, page: 406, stat: Journal Article,

Interrater reliability issues in multicenter trials .2. Statistical procedures used in VA Cooperative Study #394
Edson, R; Lavori, P; Tracy, K; Adler, LA; Rotrosen, J
1996 NOV ;32(3):436-436, Psychopharmacology bulletin
— id: 52729, year: 1996, vol: 32, page: 436, stat: Journal Article,

The relationship between clozapine and obsessive-compulsive disorder
Levin Z; Hwang MY; Rotrosen J
1996 Jan-Feb;37(1):74-74, Comprehensive psychiatry
— id: 23582, year: 1996, vol: 37, page: 74, stat: Journal Article,

Antioxidant treatment of tardive dyskinesia
Rotrosen J; Adler L; Lohr J; Edson R; Lavori P
1996 Aug;55(1-2):77-81, Prostaglandins, leukotrienes, & essential fatty acids
Tardive dyskinesia (TD) is a frequently occurring side effect of treatment with neuroleptic antipsychotic drugs. TD is a persistent and often irreversible syndrome characterized by abnormal movements, including lingual and orofacial dyskinesia, grimacing, tics, choreic movements of the limbs and trunk, and athetosis and dystonia. In some patients the muscles of respiration and speech may also be involved. There is no established treatment for TD
— id: 23581, year: 1996, vol: 55, page: 77, stat: Journal Article,

Amphetamine and negative symptoms of schizophrenia
Sanfilipo M; Wolkin A; Angrist B; van Kammen DP; Duncan E; Wieland S; Cooper TB; Peselow ED; Rotrosen J
1996 Jan;123(2):211-214, Psychopharmacology
The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia. Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale, the Abrams and Taylor Scale, and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine (n = 26) or placebo (n = 11). Our results indicated that amphetamine administration generally did not improve negative symptoms, even when accounting for changes in positive symptoms. However, greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment. Therefore, amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe
— id: 23583, year: 1996, vol: 123, page: 211, stat: Journal Article,

Interrater reliability issues in multicenter trials .1. Theoretical concepts and operational procedures in VA Cooperative Study #394
Tracy, K; Adler, LA; Rotrosen, J; Edson, R; Lavori, P
1996 NOV ;32(3):526-526, Psychopharmacology bulletin
— id: 52731, year: 1996, vol: 32, page: 526, stat: Journal Article,

Blunted change in cerebral glucose utilization after haloperidol treatment in schizophrenic patients with prominent negative symptoms
Wolkin A; Sanfilipo M; Duncan E; Angrist B; Wolf AP; Cooper TB; Brodie JD; Laska E; Rotrosen JP
1996 Mar;153(3):346-354, American journal of psychiatry
OBJECTIVE: The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerebral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical antipsychotic effect. METHOD: Cerebral glucose utilization, as determined by position emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. RESULTS: Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. CONCLUSIONS: Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences
— id: 7060, year: 1996, vol: 153, page: 346, stat: Journal Article,

NEW ANTIPSYCHOTICS TREATMENTS FOR SCHIZOPHRENIA - PANEL DISCUSSION - QUESTIONS FROM THE AUDIENCE
BORISON, RL; ROTROSEN, J; ERESHEFSKY, L; MCEVOY, JP; SCHOOLER; OPLER, LA
1995 MAY ;25(5):311-313, Psychiatric annals
— id: 87296, year: 1995, vol: 25, page: 311, stat: Journal Article,

THE IMPORTANCE OF SIDE-EFFECTS IN THE DEVELOPMENT OF NEW ANTIPSYCHOTIC-DRUGS
ROTROSEN, J; ADLER, L
1995 MAY ;25(5):306-310, Psychiatric annals
— id: 87295, year: 1995, vol: 25, page: 306, stat: Journal Article,

TRAINING RATERS TO ASSESS NEUROLEPTIC-INDUCED AKATHISIA USING STANDARDIZED VIDEOTAPES
ADLER, LA; NIERENBERA, AA; FAVA, M; HANNIBAL, J; ROTROSEN, J
1994 MAY 1 ;35(9):696-696, Biological psychiatry
— id: 52474, year: 1994, vol: 35, page: 696, stat: Journal Article,

VITAMIN-E TREATMENT OF TD - DEVELOPMENT OF A VA COOPERATIVE STUDY
ADLER, LA; ROTROSEN, J; LAVORI, P; EDSON, R
1994 MAY 1 ;35(9):730-731, Biological psychiatry
— id: 52478, year: 1994, vol: 35, page: 730, stat: Journal Article,

Vitamin E in tardive dyskinesia: Effects of longer term treatment
Adler, Lenard A.; Peselow, Eric D.; Angrist, Burt; Rosenthal, Michele; Rotrosen, John
1994 ;30(1):87-87, Psychopharmacology bulletin
— id: 106729, year: 1994, vol: 30, page: 87, stat: Journal Article,

NEUROLOGICAL SOFT SIGNS IN SCHIZOPHRENIA - RELATIONSHIP TO THOUGHT-DISORDER
DUNCAN, E; SANFILIPO, M; WIELAND, S; ANGRIST, B; ROTROSEN, J
1994 MAY 1 ;35(9):715-715, Biological psychiatry
— id: 52476, year: 1994, vol: 35, page: 715, stat: Journal Article,

Persistent psychosis after reduction in pre- and post-synaptic dopaminergic function
Wolkin A; Duncan E; Sanfilipo M; Wieland S; Cooper TB; Rotrosen J
1994 ;95(1):49-61, Journal of neural transmission
The purpose of this study was to evaluate the hypothesis that neuroleptic non-response in the face of 'adequate' DA post-synaptic receptor blockade reflects failure of regulatory mechanisms to decrease DA pre-synaptic activity. Eight chronic schizophrenics, meeting rigorous criteria for neuroleptic non-response, were treated for four weeks with alpha-methylparatyrosine as an adjunct to their previously stable neuroleptic dose. Treatment with AMPT produced a prompt decrease in plasma HVA that was, on average, 72% lower at the end of the study. While there was also strong clinical evidence of reduction in central dopaminergic activity (both a significant reduction in dyskinetic movements and increase in extrapyramidal symptoms), there was virtually no change in severity of psychotic symptoms. Thus, in this group of non-responders, psychotic symptoms persisted despite both extensive dopamine post-synaptic receptor blockade and marked reduction of presynaptic activity. These symptoms may not be directly DA dependent
— id: 23584, year: 1994, vol: 95, page: 49, stat: Journal Article,

Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology
Wolkin A; Sanfilipo M; Angrist B; Duncan E; Wieland S; Wolf AP; Brodie JD; Cooper TB; Laska E; Rotrosen JP
1994 Sep 1;36(5):317-325, Biological psychiatry
The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a placebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparent relationship between the effects of amphetamine-induced changes in regional cerebral metabolism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporesponsivity to stimulant challenge, however
— id: 8462, year: 1994, vol: 36, page: 317, stat: Journal Article,

Vitamin E treatment of tardive dyskinesia
Adler LA; Peselow E; Rotrosen J; Duncan E; Lee M; Rosenthal M; Angrist B
1993 Sep;150(9):1405-1407, American journal of psychiatry
OBJECTIVE: The authors studied the effects of vitamin E treatment of tardive dyskinesia; earlier studies have produced contradictory results. METHOD: Twenty-eight patients with tardive dyskinesia were treated in a double-blind, parallel-group comparison study of 8-12 weeks of treatment with vitamin E (1600 IU/day) or matching placebo capsules. RESULTS: The Abnormal Involuntary Movement Scale scores of the patients treated with vitamin E improved significantly compared to the scores of the patients given placebo. CONCLUSIONS: These results support earlier findings of the efficacy of vitamin E in treating tardive dyskinesia
— id: 8277, year: 1993, vol: 150, page: 1405, stat: Journal Article,

Plasma homovanillic acid in neuroleptic responsive and nonresponsive schizophrenics
Duncan E; Wolkin A; Angrist B; Sanfilipo M; Wieland S; Cooper TB; Rotrosen J
1993 Oct 15;34(8):523-528, Biological psychiatry
Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic responsive and nonresponsive schizophrenics in order to delineate parameters of dopamine regulation, which may underlie differences in neuroleptic responsivity. Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of treatment. Subjects were pretreated with debrisoquin in order to reduce the peripheral production of HVA. The responders had an initial rise in HVA at 24 hr after first neuroleptic dose, followed by a decline back to baseline over the 6 weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic predicted treatment response; a fall in HVA at 6 weeks to below pretreatment values was associated with neuroleptic nonresponse
— id: 57549, year: 1993, vol: 34, page: 523, stat: Journal Article,

Elevated PLA2 activity in schizophrenics and other psychiatric patients
Noponen M; Sanfilipo M; Samanich K; Ryer H; Ko G; Angrist B; Wolkin A; Duncan E; Rotrosen J
1993 Nov 1;34(9):641-649, Biological psychiatry
We measured serum phospholipase A2 (PLA2) activity in 39 schizophrenics, 26 psychiatric controls, and 26 normal controls using a radioenzymatic assay with phosphatidylcholine as precursor. Serum PLA2 activity was significantly higher in schizophrenics (p = 0.002) and other psychiatric (including substance abusing) patients (p = 0.032) than in normal controls. Enzyme activity did not differ between the schizophrenic patients and psychiatric controls. Fifty-one percent of the schizophrenics and 46% of psychiatric controls had PLA2 values above the highest value for normal controls. In the psychiatric control group higher than normal PLA2 activities were observed in all diagnostic categories, including major depression, bipolar disorder, posttraumatic stress disorder (PTSD), and substance abuse. In the context of others' findings of increased circulating PLA2 in infectious and inflammatory conditions, these increases must be viewed as disease nonspecific. The significance of these changes and their relationship to other acute-phase protein changes needs to be clarified in future research
— id: 23585, year: 1993, vol: 34, page: 641, stat: Journal Article,

ELEVATED PLA-2 ACTIVITY IN SCHIZOPHRENICS AND PSYCHIATRIC CONTROLS
NOPONEN, M; SANFILIPO, M; SAMANICH, K; FUKUI, T; RYER, H; KO, G; ROTROSEN, J
1993 MAR 15 ;33(6A):A98-A98, Biological psychiatry
— id: 54175, year: 1993, vol: 33, page: A98, stat: Journal Article,

Acute neuroleptic-induced akathisia
Adler, Lenard A; Angrist, Burt; Rotrosen, John
Drug-induced movement disorders Mt. Kisco NY : Futura, 1992,
— id: 5274, year: 1992, vol: , page: ?, stat: Chapter,

Negative symptoms and hypofrontality in chronic schizophrenia
Wolkin A; Sanfilipo M; Wolf AP; Angrist B; Brodie JD; Rotrosen J
1992 Dec;49(12):959-965, Archives of general psychiatry
Frontal lobe dysfunction is widely suspected to underlie negative symptoms of schizophrenia. This hypothesis is based largely on long-standing observations of the similarities between the effects of frontal lobe lesions and negative symptoms. However, there is little direct evidence specifically for such an association in schizophrenic patients. We measured the relationship between decreased relative prefrontal cortex glucose metabolism (hypofrontality) using positron emission tomography and evaluated the severity of negative symptoms in 20 chronic schizophrenics who underwent scanning while not receiving neuroleptic drugs. We found a close relationship between negative symptoms and prefrontal hypometabolism, particularly in the right dorsolateral convexity. This association was regionally specific. Furthermore, there was no evidence that this relationship was an artifact of age, cerebral atrophy, or severity of positive symptoms
— id: 57503, year: 1992, vol: 49, page: 959, stat: Journal Article,

Lack of efficacy of d-propranolol in neuroleptic-induced akathisia
Adler LA; Angrist B; Fritz P; Rotrosen J; Mallya G; Lipinski JF Jr
1991 Feb;4(2):109-115, Neuropsychopharmacology
d-Propranolol lacks clinically significant beta-adrenergic receptor blocking properties, but has the same membrane stabilizing effects as racemic (d,l) propranolol. To assess the role of beta-blockade versus membrane stabilization or other shared nonspecific effects in the therapeutic action of propranolol in neuroleptic-induced akathisia (NIA) we treated 11 patients with NIA in a crossover, double-blind study of d-propranolol versus placebo. Akathisia scores were unchanged after both d-propranolol and placebo. Eight patients were subsequently treated in a nonblind manner with racemic propranolol, with a significant reduction in akathisia scores. These findings suggest that beta-blockade, not membrane stabilization or other shared nonspecific effects, contributes to the efficacy of propranolol in NIA
— id: 23587, year: 1991, vol: 4, page: 109, stat: Journal Article,

Efficacy of betaxolol in neuroleptic-induced akathisia
Adler LA; Angrist B; Rotrosen J
1991 Nov;39(2):193-198, Psychiatry research
Betaxolol, a beta 1-selective antagonist, produced marked improvement in eight patients with neuroleptic-induced akathisia. No further improvement was seen with subsequent propranolol treatment. These findings, along with the results of prior studies of betaxolol and metoprolol, suggest that blockade of central beta 1-receptors may be sufficient for efficacy in akathisia
— id: 23586, year: 1991, vol: 39, page: 193, stat: Journal Article,

Studies on the time course and efficacy of beta-blockers in neuroleptic-induced akathisia and the akathisia of idiopathic Parkinson's disease
Adler LA; Angrist B; Weinreb H; Rotrosen J
1991 ;27(2):107-111, Psychopharmacology bulletin
This investigation reports pilot data on two points originally raised in the earliest reports of the efficacy of beta-blockers in akathisia: their potential utility in the akathisia of idiopathic Parkinson's disease and the possibility of determining a central vs. a peripheral site of action by comparing the time course of the effects of lipophilic and hydrophilic agents. Akathisia improved in 4 patients with idiopathic Parkinson's disease after low dose propranolol treatment. Six patients with neuroleptic-induced akathisia were treated with the hydrophilic beta-blocker nadolol. Effects on akathisia occurred, but evolved much more slowly than after treatment with lipophilic agents, such as propranolol and metoprolol, thus suggesting a central site of action
— id: 23589, year: 1991, vol: 27, page: 107, stat: Journal Article,

Stability of resting deoxyglucose metabolic values in PET studies of schizophrenia
Bartlett EJ; Barouche F; Brodie JD; Wolkin A; Angrist B; Rotrosen J; Wolf AP
1991 May;40(1):11-20, Psychiatry research
Positron emission tomography (PET) and the deoxyglucose method were used to determine the test-retest stability of regional cerebral glucose metabolism in 8 male schizophrenic patients and 11 normal control subjects, scanned twice under baseline (resting) conditions. Normal and schizophrenic subjects showed comparable stability of regional metabolism. When the regional values were scaled to compensate for the effects of changes in whole brain metabolism, the resulting mean regional changes were reduced to about 1-2% in both groups. This study demonstrates that the baseline resting state is an appropriate reference state for schizophrenic subjects in deoxyglucose PET experiments
— id: 14038, year: 1991, vol: 40, page: 11, stat: Journal Article,

Serum iron levels and akathisia [see comments]
Nemes ZC; Rotrosen J; Angrist B; Peselow E; Schoentag R
1991 Feb 15;29(4):411-413, Biological psychiatry
— id: 14130, year: 1991, vol: 29, page: 411, stat: Journal Article,

SERUM IRON AND AKATHESIA - REPLY
NEMES, Z; ROTROSEN, J; WHITE, T; ANGRIST, B; PESELOW, E; SHOENTAG, R; BROWN, KW
1991 NOV 15 ;30(10):1064-1065, Biological psychiatry
— id: 51532, year: 1991, vol: 30, page: 1064, stat: Journal Article,

Disappearance of memory deficits in outpatient depressives responding to imipramine
Peselow ED; Corwin J; Fieve RR; Rotrosen J; Cooper TB
1991 Mar;21(3):173-183, Journal of affective disorders
We evaluated learning and memory in 50 depressed patients prior to and following 4 week treatment with imipramine compared to 21 normal controls tested at corresponding times. At baseline, the depressives did worse than normals on most memory tasks with the difficult memory tasks, regardless of store, modality or type of task best distinguishing between depressive and normal memory. Following imipramine treatment, responders performed better than nonresponders on the difficult memory tasks, and not significantly differently from controls on most tasks. This, as well as the fact that the responders improved to a greater degree than controls on most measures (in a few cases the difference was statistically significant) and the fact that at 4 weeks complete responders to imipramine did significantly better than partial responders to imipramine, indicates that relief from depression is highly related to improved memory functioning. The finding that complete responders to imipramine were not significantly worse than normal controls suggests that imipramine did not have significant adverse effects on memory
— id: 14124, year: 1991, vol: 21, page: 173, stat: Journal Article,

The prevalence of tardive dyskinesia
Woerner MG; Kane JM; Lieberman JA; Alvir J; Bergmann KJ; Borenstein M; Schooler NR; Mukherjee S; Rotrosen J; Rubinstein M; et al.
1991 Feb;11(1):34-42, Journal of clinical psychopharmacology
A total of 2250 subjects from psychiatric and geriatric settings was examined for abnormal involuntary movements by the same team of trained raters employing a standard examination technique and rating scale. 'Spontaneous' dyskinesia rates were 1.3% among 400 healthy elderly people surveyed at senior citizens centers, 4.8% among medical geriatric inpatients and ranged from 0 to 2% among psychiatric patients never exposed to neuroleptics. For samples of neuroleptic-treated patients, prevalence rates ranged from 13.3% among patients at a voluntary psychiatric hospital to 36.1% among state hospital patients. Logistic regression analyses revealed a large effect of age on tardive dyskinesia prevalence and an interaction of age with sex. Among younger subjects, men had higher rates; among subjects over age 40, rates were higher for women. Edentulousness and presence of other neurological disorders were possible contributors to high rates for the elderly. Even with control for age, sex and duration of neuroleptic exposure, prevalence differed markedly across study site
— id: 23588, year: 1991, vol: 11, page: 34, stat: Journal Article,

Metoprolol versus propranolol
Adler LA; Angrist B; Rotrosen J
1990 Mar 15;27(6):673-675, Biological psychiatry
— id: 23592, year: 1990, vol: 27, page: 673, stat: Journal Article,

Effects of buspirone in seven schizophrenic subjects
Brody D; Adler LA; Kim T; Angrist B; Rotrosen J
1990 Feb;10(1):68-69, Journal of clinical psychopharmacology
— id: 23593, year: 1990, vol: 10, page: 68, stat: Journal Article,

Psychological and behavioral impact among intravenous drug users of learning HIV test results
Casadonte PP; Des Jarlais DC; Friedman SR; Rotrosen JP
1990 Apr;25(4):409-426, International journal of the addictions
In 1984 as part of a New York City study to examine the prevalence of HIV infection in a substance-abusing population and to test the validity of HIV screening kits, 94 patients at the New York VAMC were tested. Results were made available to 50 (35 seronegative, 15 seropositive) patients in January 1986. Psychological and behavioral impact of learning test results was assessed using standardized psychiatric rating scales. A comparison group of 31 nontested subjects were also evaluated. Ratings were done preresults, approximately 1-2 weeks after results, and 8-10 weeks after informing patients of their HIV status. No major stress reactions were observed. Seropositives experienced a higher level of anxiety 1-2 weeks after learning results but anxiety generally diminished; they made significant behavior changes which were maintained. Seronegatives experienced relief and maintained IV drug risk reduction behavior. Anxiety about contracting AIDS increased in nontested subjects as the study progressed
— id: 21390, year: 1990, vol: 25, page: 409, stat: Journal Article,

Disorders of decision in affective disease: an effect of beta-adrenergic dysfunction?
Corwin J; Peselow E; Feenan K; Rotrosen J; Fieve R
1990 Apr 15;27(8):813-833, Biological psychiatry
We investigated response bias (defined as the decision rule subjects adopt when uncertain) in two experiments using a variant of Signal Detection Theory (SDT) with the discrimination measure d'L and the bias measure CL, under which it is possible to independently evaluate discrimination and response bias. In the first experiment, manics, depressed subjects, and matched psychiatrically normal controls were tested with a recognition memory task with easier and more difficult components before and after 1 month of appropriate pharmacological treatment. This experiment showed that abnormally conservative bias was characteristic of depression and liberal (yea-saying) bias was found in mania regardless of severity of illness; discrimination deficits were found only when symptoms were severe. After treatment, aspects of discrimination worsened in both hypomanic and depressed nonresponders whereas response bias remained unchanged in these patients. In both groups of responders, improvements in response bias were more dramatic than improvements in discrimination. In the second experiment, psychiatrically normal hypertensives were tested with a Sternberg short-term memory scanning task on and off treatment with the centrally active beta-blocker propranolol. This experiment showed that treatment with propranolol modeled the bias deficit of depression; that is, bias became more conservative. Both sets of results suggest that disorders of decision may be modulated by beta-adrenergic function
— id: 23590, year: 1990, vol: 27, page: 813, stat: Journal Article,

Nifedipine in the treatment of tardive dyskinesia
Duncan E; Adler L; Angrist B; Rotrosen J
1990 Dec;10(6):414-416, Journal of clinical psychopharmacology
There have been several case reports of improvement in tardive dyskinesia (TD) after treatment with calcium-blocking agents. We have conducted prior single-blind (rater-blind) studies of verapamil and diltiazem and found a statistically significant improvement in TD with verapamil, and a small improvement that did not reach statistical improvement after diltiazem treatment. We now report a single-blind (rater-blind) study of a third calcium antagonist, nifedipine, in the treatment of TD. Nifedipine (30-60 mg/day) was administered to eight schizophrenic patients with TD. Mean AIMS scores on items 1-7 decreased from 12.9 +/- 2.0 (SD) at baseline to 10.8 +/- 2.7 after treatment (t = 3.66, p = 0.01). All subjects were able to tolerate the maximal dose of nifedipine without significant side effects. TD is known to be affected by drugs that affect dopamine neurotransmission. Several lines of pre-clinical and clinical evidence suggest interactions between the calcium antagonists and the CNS dopamine system and provide a possible explanation for the effects on TD seen with calcium antagonists
— id: 8225, year: 1990, vol: 10, page: 414, stat: Journal Article,

Basal ganglia calcification in schizophrenia
Fernandez-Bouzas A; Angrist B; Hemdal P; Adler LA; Rotrosen J
1990 Mar 15;27(6):682-685, Biological psychiatry
— id: 23591, year: 1990, vol: 27, page: 682, stat: Journal Article,

Scopolamine and olfactory function
Serby M; Flicker C; Rypma B; Weber S; Rotrosen JP; Ferris SH
1990 Jul 1;28(1):79-82, Biological psychiatry
— id: 23569, year: 1990, vol: 28, page: 79, stat: Journal Article,

Effects of a specific beta 2-receptor blocker in neuroleptic-induced akathisia
Adler L; Duncan E; Angrist B; Hemdal P; Rotrosen J; Slotnick V
1989 Jan;27(1):1-4, Psychiatry research
To assess the role of blockade of beta-receptor subpopulations in the treatment of neuroleptic-induced akathisia (NIA), the specific beta 2-antagonist ICI 118,551 was compared to placebo in a double-blind study. After a baseline evaluation on placebo, patients were treated with ICI 118,551 or placebo. Five of six patients treated with ICI 118,551 showed improvements in NIA, while only one of four patients improved on placebo. Patients were then treated openly with propranolol, a mixed beta 1, beta 2-antagonist. Compared to ICI 118,551, no further improvement on objective measures of akathisia was seen on propranolol. Mean subjective assessments of NIA declined on propranolol, but changes were variable and not statistically significant
— id: 23601, year: 1989, vol: 27, page: 1, stat: Journal Article,

Neuroleptic-induced akathisia: a review
Adler LA; Angrist B; Reiter S; Rotrosen J
1989 ;97(1):1-11, Psychopharmacology
Neuroleptic-induced akathisia (NIA) is a relatively common side effect of neuroleptics, in which patients complain of a subjective sense of restlessness usually referable to the legs and have characteristic motor movements. This paper will review: 1) history of spontaneously occurring syndromes of pathologic restlessness and NIA, 2) the clinical significance of NIA, 3) issues concerning the diagnosis and quantification of NIA, 4) treatments of NIA and 5) possible future directions for research in this area. Special attention will be paid to newer treatments for this syndrome, specifically beta-blockers
— id: 23600, year: 1989, vol: 97, page: 1, stat: Journal Article,

Akathisia: selective beta-blockers and rating instruments
Adler LA; Duncan E; Kim A; Hemdal P; Rotrosen J; Angrist B
1989 ;25(3):451-456, Psychopharmacology bulletin
beta-Blockers, particularly propranolol, have been shown to be an effective treatment for neuroleptic-induced akathisia (NIA). To examine the relative contribution of beta-1 and beta-2 receptor blockade to the therapeutic effect of propranolol, we studied a beta-1 selective agent (low dose metoprolol) and a beta-2 specific blocker (ICI 118,551). Both agents ameliorated NIA. To further evaluate instruments for quantifying NIA we compared (a) two sets of clinical ratings during the metoprolol study and (b) clinical and electromechanical ratings of NIA during the ICI 118,551 study. The changes in clinical ratings of NIA after metoprolol were similar for most patients; however, the changes in electromechanical and clinical ratings after ICI 118,551 were similar in less than half of the patients studied
— id: 23599, year: 1989, vol: 25, page: 451, stat: Journal Article,

Treatment of extrapyramidal side-effects
Adler LA; Duncan E; Reiter S; Rotrosen J; Angrist B
1989 Aug;155(11):269-269, British journal of psychiatry
— id: 23594, year: 1989, vol: 155, page: 269, stat: Journal Article,

NEUROLEPTIC-INDUCED AKATHISIA - REPLY
Adler, LA; Angrist, B; Reiter, S; Rotrosen, J
1989 Aug 15;99(1):135-135, Psychopharmacology
— id: 31790, year: 1989, vol: 99, page: 135, stat: Journal Article,

Neuroleptic augmentation with alprazolam: clinical effects and pharmacokinetic correlates
Douyon R; Angrist B; Peselow E; Cooper T; Rotrosen J
1989 Feb;146(2):231-234, American journal of psychiatry
Alprazolam added to stable doses of neuroleptics in nine schizophrenic patients was associated with a 20%-30% mean reduction in positive and negative symptoms, although clinical response was variable and in some patients particularly brisk. The authors examined the possibilities of a pharmacokinetic effect of alprazolam on neuroleptic plasma levels and of a clinical effect of alprazolam. The modest increase in mean neuroleptic plasma levels did not correlate with clinical change, but those patients with the highest alprazolam plasma levels tended to show more robust clinical responses
— id: 23597, year: 1989, vol: 146, page: 231, stat: Journal Article,

ECT and Parkinson's disease revisited: a "naturalistic" study [see comments]
Douyon R; Serby M; Klutchko B; Rotrosen J
1989 Nov;146(11):1451-1455, American journal of psychiatry
In an open study, seven patients with Parkinson's disease received ECT for major depression. Both the motor dysfunction and the mood impairment of these patients improved following an average of seven ECT sessions. Significant improvement in motor function occurred after only two treatments. All aspects of Parkinson's disease improved significantly after ECT. Older patients showed greater improvement in motor function. The authors conclude that the therapeutic utility of ECT in depressed and nondepressed patients with Parkinson's disease should be further evaluated
— id: 10430, year: 1989, vol: 146, page: 1451, stat: Journal Article,

Efficacy of low-dose metoprolol in neuroleptic-induced akathisia
Kim A; Adler L; Angrist B; Rotrosen J
1989 Aug;9(4):294-296, Journal of clinical psychopharmacology
Recent studies have shown that the beta-blockers can be effective treatments for neuroleptic-induced akathisia. However, the relative contributions of beta-1 versus beta-2 blockade to the therapeutic effect of beta-blockers remains unclear. We treated nine patients who had neuroleptic-induced akathisia with low doses (25-100 mg/day) of the beta-blocker metoprolol. At these doses metoprolol causes selective blockade of beta-1 receptors. Seven patients improved after metoprolol; no further substantial changes were seen after subsequent treatment with propranolol. This finding suggests that neuroleptic-induced akathisia can be improved by selective beta-1 blockade
— id: 23595, year: 1989, vol: 9, page: 294, stat: Journal Article,

GM1 ganglioside as a potential treatment in tardive dyskinesia
Peselow ED; Irons S; Rotrosen J; Alonso MT; Dorsey F
1989 ;25(2):277-280, Psychopharmacology bulletin
— id: 23598, year: 1989, vol: 25, page: 277, stat: Journal Article,

Effects of verapamil on tardive dyskinesia and psychosis in schizophrenic patients
Reiter S; Adler L; Angrist B; Peselow E; Rotrosen J
1989 Jan;50(1):26-27, Journal of clinical psychiatry
Nine hospitalized schizophrenic patients with tardive dyskinesia were treated with the calcium-channel antagonist verapamil under single-blind conditions. The tardive dyskinesia and activation scores decreased, and the anxiety/depression scores increased. The changes were small but statistically significant
— id: 23602, year: 1989, vol: 50, page: 26, stat: Journal Article,

Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia
Wolkin A; Barouche F; Wolf AP; Rotrosen J; Fowler JS; Shiue CY; Cooper TB; Brodie JD
1989 Jul;146(7):905-908, American journal of psychiatry
Because CNS neuroleptic concentration cannot be directly measured in patients, the relation between clinical response and extent of dopamine receptor blockade is unknown. This relationship is critical in ascertaining whether nonresponse to neuroleptics is the result merely of inadequate CNS drug levels or of more basic biological differences in pathophysiology. Using [18F]N-methylspiroperidol and positron emission tomography, the authors assessed dopamine receptor occupancy in 10 schizophrenic patients before and after treatment with haloperidol. Responders and nonresponders had virtually identical indices of [18F]N-methylspiroperidol uptake after treatment, indicating that failure to respond clinically was not a function of neuroleptic uptake or binding in the CNS
— id: 8395, year: 1989, vol: 146, page: 905, stat: Journal Article,

Dopamine receptor occupancy and plasma haloperidol levels
Wolkin A; Brodie JD; Barouche F; Rotrosen J; Wolf AP; Smith M; Fowler J; Cooper TB
1989 May;46(5):482-484, Archives of general psychiatry
— id: 23596, year: 1989, vol: 46, page: 482, stat: Journal Article,

Effects of calcium-channel antagonists on tardive dyskinesia and psychosis
Adler L; Duncan E; Reiter S; Angrist B; Peselow E; Rotrosen J
1988 ;24(3):421-425, Psychopharmacology bulletin
— id: 23606, year: 1988, vol: 24, page: 421, stat: Journal Article,

Neuroleptic-induced akathisia: propranolol versus benztropine
Adler LA; Reiter S; Corwin J; Herndal P; Angrist B; Rotrosen J
1988 Jan 15;23(2):211-213, Biological psychiatry
— id: 23603, year: 1988, vol: 23, page: 211, stat: Journal Article,

CNS EFFECTS OF BETA-BLOCKADE - A COMPARATIVE-STUDY (PSYCHOMETRIC AND COGNITIVE)
ADLER, L; ROTROSEN, JP; HEMDAL, P; CORWIN, J; PESELOW, E; REITANO, JM; REES, RS
1988 FEB 29 ;140(6):52-54, Postgraduate medicine
— id: 41817, year: 1988, vol: 140, page: 52, stat: Journal Article,

Preliminary studies of clonidine in psychotic patients
Angrist B; Smith M; Adler L; Peselow E; Reitano J; Rotrosen J
1988 ;71(2):115-121, Journal of neural transmission
Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study
— id: 23604, year: 1988, vol: 71, page: 115, stat: Journal Article,

Regional glucose metabolism in chronic schizophrenia
Brodie JD; Wolkin A; Wolf AP; Volkow N; Russell JA; Van Gelder P; Jaeger J; Fowler J; Rotrosen J; Cancro R
1988 ;3(1):54-54, American journal of physiologic imaging
— id: 11210, year: 1988, vol: 3, page: 54, stat: Journal Article,

Clinical stages of dementia and the dexamethasone suppression test
Serby M; Zucker D; Kaufman M; Franssen E; Duvvi K; Rypma B; Rotrosen J
1988 ;12(5):833-836, Progress in neuro-psychopharmacology & biological psychiatry
1. This study was undertaken to evaluate the relationship between clinical aspects of primary degenerative dementia and suppression or non-suppression in the dexamethasone suppression test. 2. We studied 34 male patients with primary degenerative dementia (as diagnosed by DSM-III criteria). Dexamethasone 1 mg p.o. was administered at 11:00 PM and blood was drawn for cortisol determination at 4:00 PM the next day. 3. CLINICAL FACTORS INCLUDED: age, age at onset, duration of dementia, history of psychiatric illness, severity as measured by Global Deterioration Scale (GDS) score, and 'malignancy' of dementia (rated by years of onset to institutionalization and as a ratio of Global Deterioration Scale to duration of primary degenerative dementia). 4. RESULTS: 56% of primary degenerative dementia patients failed to suppress. The highest degree of non-suppression was seen in Global Deterioration Scale 5 and 6 subjects (Table). 5. An unexpected finding was that a large number of Global Deterioration Scale 7 patients demonstrated normal post-dexamethasone suppression of the hypothalamic-pituitary-adrenal axis. 6. Some contradictions in previously reported studies may be explained by this pattern
— id: 23605, year: 1988, vol: 12, page: 833, stat: Journal Article,

Low frontal glucose utilization in chronic schizophrenia: a replication study
Wolkin A; Angrist B; Wolf A; Brodie JD; Wolkin B; Jaeger J; Cancro R; Rotrosen J
1988 Feb;145(2):251-253, American journal of psychiatry
Frontal/posterior ratios of cerebral glucose metabolism as determined by positron emission tomography were significantly lower in 13 chronic schizophrenic patients than in eight normal control subjects, as were absolute metabolic rates in both the frontal and posterior regions. The differences were not accounted for by cerebral atrophy
— id: 11197, year: 1988, vol: 145, page: 251, stat: Journal Article,

Noradrenergic mechanisms in akathisia: treatment with propranolol and clonidine
Adler L; Angrist B; Peselow E; Corwin J; Rotrosen J
1987 ;23(1):21-25, Psychopharmacology bulletin
— id: 23615, year: 1987, vol: 23, page: 21, stat: Journal Article,

Clonidine in neuroleptic-induced akathisia
Adler LA; Angrist B; Peselow E; Reitano J; Rotrosen J
1987 Feb;144(2):235-236, American journal of psychiatry
Six hospitalized patients with neuroleptic-induced akathisia were treated with clonidine under single-blind conditions. Akathisia and anxiety at maximum clonidine dose were significantly lower than at baseline, although it was difficult to differentiate specific therapeutic effects from sedation
— id: 23612, year: 1987, vol: 144, page: 235, stat: Journal Article,

Pindolol and propranolol in neuroleptic-induced akathisia
Adler LA; Reiter S; Angrist B; Rotrosen J
1987 Sep;144(9):1241-1242, American journal of psychiatry
— id: 23607, year: 1987, vol: 144, page: 1241, stat: Journal Article,

TIME COURSE OF EFFECTS OF CLONIDINE - REPLY
ADLER, LA; ANGRIST, B; PESELOW, E; REITANO, J; ROTROSEN, J
1987 ;144(11):1519-1519, American journal of psychiatry
— id: 106734, year: 1987, vol: 144, page: 1519, stat: Journal Article,

DIFFERENTIAL-EFFECTS OF PROPRANOLOL AND BENZTROPINE IN PATIENTS WITH NEUROLEPTIC-INDUCED AKATHISIA
Adler, LA; Reiter, S; Corwin, J; Hemdal, P; Angrist, B; Rotrosen, J
1987 Dec 15;23(3):519-521, Psychopharmacology bulletin
— id: 31301, year: 1987, vol: 23, page: 519, stat: Journal Article,

PET STUDIES IN SCHIZOPHRENIA
Brodie, JD; Wolf, AP; Wolkin, A; Arnett, CD; Angrist, B; Fowler, J; Smith, M; Russell, J; Logan, J; Christman, D; Rotrosen, J; Volkow, N
1987 Apr;32(1-2):445-445, International journal of neuroscience
— id: 31391, year: 1987, vol: 32, page: 445, stat: Journal Article,

Lack of effect of carbidopa on plasma homovanillic acid in normal subjects
Brody D; Angrist B; Rotrosen J; Schweitzer J; Friedhoff AJ
1987 Jun;21(2):185-187, Psychiatry research
— id: 23609, year: 1987, vol: 21, page: 185, stat: Journal Article,

Olfaction and hemodialysis: baseline and acute treatment decrements
Conrad P; Corwin J; Katz L; Serby M; LeFavour G; Rotrosen J
1987 ;47(2):115-118, Nephron
The effect of hemodialysis (HD) on olfactory recognition and memory function was investigated in people receiving chronic HD treatment. Fifteen subjects were given an olfactory recognition task 0.5 h before and 0.5 h after a dialysis session in counterbalanced order. Ten dialysis patients received a verbal recall task twice. Ten age-matched normal subjects received the olfactory task twice. Results were: (1) olfactory scores in the HD group were significantly lower than control subjects scores; (2) within the dialysis sample, olfactory identification scores were significantly lower after treatment than before, and (3) there were no parallel decreases in memory performance of the dialysis group after a HD treatment. We therefore conclude that those subjects receiving HD treatment demonstrate acute and chronic deficits in olfactory recognition which are unlikely to be due to fatigue, cognitive disequilibrium, anticoagulant treatment or high levels of uremic toxins
— id: 23613, year: 1987, vol: 47, page: 115, stat: Journal Article,

Double blind controlled trials of cholecystokinin octapeptide in neuroleptic-refractory schizophrenia
Peselow E; Angrist B; Sudilovsky A; Corwin J; Siekierski J; Trent F; Rotrosen J
1987 ;91(1):80-84, Psychopharmacology
A group of 14 schizophrenics who remained symptomatic after neuroleptic treatment received either 0.02 mcg/kg CCK-8 or saline placebo intravenously. Thereafter, 13 received the alternative infusion as a crossover treatment. A second group of 16 such patients received 0.04 mcg/kg CCK-8 or saline intravenously and, thereafter, 14 of these received the alternative infusion as a crossover treatment. Psychopathology was rated prior to, 2-3 h post, and on days 3, 5 and 7 after each infusion. Ratings consisted of the BPRS, the Abrams and Taylor Scale for Emotional Blunting, the Hamilton Anxiety Scale and a Schneiderian 'Positive' symptom scale abstracted from the President State Examination. Parallel groups and cross over design analyses failed to show efficacy for CCK-8
— id: 23616, year: 1987, vol: 91, page: 80, stat: Journal Article,

Atenolol and propranolol in neuroleptic-induced akathisia
Reiter S; Adler L; Angrist B; Corwin J; Rotrosen J
1987 Aug;7(4):279-280, Journal of clinical psychopharmacology
— id: 23608, year: 1987, vol: 7, page: 279, stat: Journal Article,

Essential fatty acids, prostaglandins, and nonsteroidal antiinflammatory agents: physiological and behavioral interactions
Segarnick D; Rotrosen J
1987 Feb;11(1):19-24, Alcoholism: clinical & experimental research
— id: 23611, year: 1987, vol: 11, page: 19, stat: Journal Article,

Effects of amphetamine on local cerebral metabolism in normal and schizophrenic subjects as determined by positron emission tomography
Wolkin A; Angrist B; Wolf A; Brodie J; Wolkin B; Jaeger J; Cancro R; Rotrosen J
1987 ;92(2):241-246, Psychopharmacology
The effects of d-amphetamine (0.5 mg/kg PO) on regional cerebral glucose utilization were measured with Positron Emission Tomography (PET). Subjects included ten chronic schizophrenics and six controls who received amphetamine, and six chronic schizophrenics and nine controls who received placebo or no treatment. Amphetamine decreased glucose metabolism in all regions studied (frontal, temporal, and striatal) in normal and schizophrenic subjects. The metabolic effects of amphetamine were correlated with plasma level of the drug. Cortical atrophy was associated with a blunted metabolic response
— id: 23614, year: 1987, vol: 92, page: 241, stat: Journal Article,

Essential fatty acid supplementation during early alcohol abstinence
Wolkin A; Segarnick D; Sierkierski J; Manku M; Horrobin D; Rotrosen J
1987 Feb;11(1):87-92, Alcoholism: clinical & experimental research
Interactions between ethanol, prostaglandins, and essential fatty acids (EFA) have led to the hypothesis that acute alcohol withdrawal and the sequelae of chronic alcoholism may be related to an EFA/prostaglandin deficiency. To test this hypothesis, EFA profiles in blood-lipid fractions, serum liver enzymes, cognitive function, and alcohol craving were measured in 27 acutely abstinent alcoholics before and after a 3-week double-blind trial of EFA supplementation. Upon entry into the study, alcoholics had significant differences in EFA levels as compared to normal controls, and serum levels of liver enzymes tended to correlate with these EFA levels. After 21 days, cognitive function, alcohol craving, and liver enzymes all improved in both the EFA and placebo groups; most EFA levels also approached normal values. There were no treatment effects of EFA supplementation at the dose used
— id: 23610, year: 1987, vol: 11, page: 87, stat: Journal Article,

A controlled assessment of propranolol in the treatment of neuroleptic-induced akathisia
Adler L; Angrist B; Peselow E; Corwin J; Maslansky R; Rotrosen J
1986 Jul;149(7):42-45, British journal of psychiatry
Twelve patients with neuroleptic-induced akathisia were treated in a randomised, double-blind, cross-over design with propranolol and matching placebo. Propranolol caused significant decrements in both subjective and objective ratings of akathisia, but not in anxiety scores. This confirms prior findings of the efficacy of propranolol in akathisia induced by neuroleptic treatment
— id: 23620, year: 1986, vol: 149, page: 42, stat: Journal Article,

BETA-BLOCKERS AS A TREATMENT FOR NEUROLEPTIC-INDUCED AKATHISIA
ADLER, L; LIPINSKI, J; ANGRIST, B; COHEN, B; PESELOW, E; ROTROSEN, J
1986 ;9(2):428-430, Clinical neuropharmacology
— id: 106735, year: 1986, vol: 9, page: 428, stat: Journal Article,

EFFECTS OF AMPHETAMINE ON LOCAL CEREBRAL METABOLISM IN NORMAL AND SCHIZOPHRENIC SUBJECTS AS DETERMINED BY POSITRON EMISSION TOMOGRAPHY USING [C-11-1] 2-DEOXY-D-GLUCOSE (C-11-2DG)
BRODIE, JD; WOLKIN, A; ANGRIST, B; WOLF, AP; JORDAN, B; JAEGER, J; CANCRO, R; ROTROSEN, J
1986 JUN ;27(6):901-901, Journal of nuclear medicine
— id: 41433, year: 1986, vol: 27, page: 901, stat: Journal Article,

OLFACTORY DEFICITS IN AD - WHAT WE KNOW ABOUT THE NOSE
CORWIN, J; SERBY, M; ROTROSEN, J
1986 NOV-DEC ;7(6):580-582, Neurobiology of aging
— id: 51309, year: 1986, vol: 7, page: 580, stat: Journal Article,

Niacin-induced flush as a measure of prostaglandin activity in alcoholics and schizophrenics
Fiedler P; Wolkin A; Rotrosen J
1986 Nov;21(13):1347-1350, Biological psychiatry
— id: 23617, year: 1986, vol: 21, page: 1347, stat: Journal Article,

The dexamethasone suppression test and response to placebo
Peselow ED; Lautin A; Wolkin A; Rohrs C; Novatt A; Siekierski J; Rotrosen J
1986 Oct;6(5):286-291, Journal of clinical psychopharmacology
The predictive value of the dexamethasone suppression test (DST) was evaluated in two consecutive double-blind, placebo-controlled trials evaluating 61 depressed inpatients randomized to either one of two drugs, sertraline or oxaprotiline, or placebo over a 4-week clinical trial. For 30 patients who completed at least 3 weeks of double-blind treatment on either drug, the initial DST was not predictive of response to drug treatment. For the 17 patients who completed at least 3 weeks of double-blind treatment on placebo, the presence of a positive DST predicted a statistically significantly poorer response to placebo as opposed to a negative DST. These preliminary findings suggest that for depressed individuals who present with a positive DST, remission without active medication is less likely and somatic treatment should be considered
— id: 23618, year: 1986, vol: 6, page: 286, stat: Journal Article,

Naltrexone and Alzheimer's disease
Serby M; Resnick R; Jordan B; Adler J; Corwin J; Rotrosen JP
1986 ;10(3-5):587-590, Progress in neuro-psychopharmacology & biological psychiatry
Naltrexone, an oral opiate antagonist, was administered to nine patients with a diagnosis of Alzheimer's-type dementia (ATD) in a two-phase design: an open dose-ranging phase and a double-blind placebo-controlled trial for patients who showed improvement during the open phase. After a three day placebo (baseline) period, patients received increasing doses of naltrexone over two weeks up to a maximum daily dose of 100 mg. Assessments were made at baseline and at daily dose of 5 mg, 50 mg and 100 mg. Testing was done 2 to 4 hours after medication was administered. Any patient who showed cognitive/behavioral improvement on a given dose of naltrexone was then treated with this dosage in a double-blind crossover comparison to placebo. Criteria for inclusion in the double-blind phase consisted of improvement on three behavioral scales and at least one cognitive test on a given dose of naltrexone. Each double-blind phase followed a one-week washout and was two weeks long. Two of the nine patients demonstrated apparent cognitive enhancement on 100 mg daily of naltrexone and were then tested in the double-blind crossover period. Only one of these patients improved during active naltrexone administration. We conclude that the opiate antagonist naltrexone in a dosage range of 5-100 mg daily is not efficacious in ATD
— id: 23571, year: 1986, vol: 10, page: 587, stat: Journal Article,

Somatostatin regulation of the CRF-ACTH-cortisol axis
Serby M; Richardson SB; Rypma B; Twente S; Rotrosen JP
1986 Aug;21(10):971-974, Biological psychiatry
— id: 23570, year: 1986, vol: 21, page: 971, stat: Journal Article,

SERIAL [F-18] N-METHYLSPIROPERIDOL (F-18 NMS) PET STUDIES MEASURE CHANGES IN ANTIPSYCHOTIC DRUG D2 RECEPTOR OCCUPANCY IN SCHIZOPHRENICS
SMITH, M; WOLF, AP; SHIUE, CY; FOWLER, JS; RUSSELL, JAG; MACGREGOR, R; ARNETT, C; LOGAN, J; WOLKIN, A; ROTROSEN, J; BRODIE, JD
1986 JUN ;27(6):880-880, Journal of nuclear medicine
— id: 41431, year: 1986, vol: 27, page: 880, stat: Journal Article,

Essential fatty acid supplementation in tardive dyskinesia
Wolkin A; Jordan B; Peselow E; Rubinstein M; Rotrosen J
1986 Jul;143(7):912-914, American journal of psychiatry
Preclinical and clinical observations suggest that enhancement of prostaglandin activity inhibits catecholamine release and may have antidyskinetic effects. A double-blind therapeutic trial with prostaglandin precursor essential fatty acids was conducted in 16 patients with tardive dyskinesia. No beneficial effects were seen
— id: 23619, year: 1986, vol: 143, page: 912, stat: Journal Article,

Efficacy of propranolol in neuroleptic-induced akathesia
Adler L; Angrist B; Peselow E; Corwin J; Rotrosen J
1985 Jun;5(3):164-166, Journal of clinical psychopharmacology
The effects of propranolol, 20 to 30 mg/day, on neuroleptic-induced akathesia were compared with those of lorazepam, 2 mg/day, and periods of no treatment. Raters were blind to treatment condition. As reported in prior open studies, propranolol was found to be dramatically effective in reducing akathesia induced by neuroleptic treatment
— id: 23624, year: 1985, vol: 5, page: 164, stat: Journal Article,

Amphetamine response and relapse risk after depot neuroleptic discontinuation
Angrist B; Peselow E; Rubinstein M; Wolkin A; Rotrosen J
1985 ;85(3):277-283, Psychopharmacology
Twenty-five schizophrenic outpatient subjects in a depot neuroleptic discontinuation study received an amphetamine challenge approximately 6 weeks after their last dose. Only five of these showed greater than three-point increases in positive symptoms on the BPRS, and all five relapsed within 30 days of the challenge. The 20 with less than three-point increases in positive symptoms showed extremely variable stability, relapsing from 20- greater than 600 days after the challenge. Thus, increase in positive symptoms after amphetamine may identify a group at risk for rapid relapse after neuroleptic discontinuation, but lack of such a response gives little prognostic information
— id: 23630, year: 1985, vol: 85, page: 277, stat: Journal Article,

Behavioral effects of phosphatidylserine in the aged Fischer 344 rat: amelioration of passive avoidance deficits without changes in psychomotor task performance
Corwin J; Dean RL 3rd; Bartus RT; Rotrosen J; Watkins DL
1985 Spring;6(1):11-15, Neurobiology of aging
A series of studies was conducted to evaluate the effects of phosphatidylserine (PS) in aged Fischer 344 rats. No effects were observed in any of four psychomotor tasks in which aged rats normally show deficits, nor on measures of shock sensitivity. However, significant dose-related effects on retention of passive avoidance were observed when PS was given both 30 min prior to training and retention. Further, in a second experiment similar positive effects were observed when PS was given only 30 min prior to training, as well as only 5 min following training. These results suggest that one effect of PS may include an ability to enhance neural events involved in the encoding or consolidation of new information into memory
— id: 23628, year: 1985, vol: 6, page: 11, stat: Journal Article,

The prevalence of tardive dyskinesia
Kane JM; Woerner M; Lieberman JA; Weinhold P; Florio W; Rubinstein M; Rotrosen J; Kurucz J; Mukherjee S; Bergmann K; et al.
1985 ;21(1):136-139, Psychopharmacology bulletin
— id: 23631, year: 1985, vol: 21, page: 136, stat: Journal Article,

Conformational changes in muscarinic receptors may produce diminished cholinergic neurotransmission and memory deficits in aged rats
Lippa AS; Loullis CC; Rotrosen J; Cordasco DM; Critchett DJ; Joseph JA
1985 Winter;6(4):317-323, Neurobiology of aging
Both clinical and laboratory studies suggest that age-related memory deficits may be due, at least in part, to disturbances in muscarinic acetylcholine (mAChR) receptors. In order to further evaluate this premise, the present studies examined the electrophysiological responses rates of hippocampal pyramidal cells to iontophoretically applied ACh in young, middle-age and aged animals. The relationship between age and muscarinic agonist and antagonist binding in the hippocampus was also examined. In addition, possible age-related changes in receptor-effector coupling were assessed by determining calmodulin levels and the activities of phospholipid methyl-transferase I and II. Analysis of electrophysiological data showed selective age-related decrements in the ability of ACh to alter burst rate but not simple spike rate. These age-related decreases in the efficacy of ACh to increase burst rate were not paralleled by decreases in mAChR density as assessed by 3H-QNB binding, but they were temporally paralleled by age-related changes in the ability of oxotremorine to inhibit 3H-QNB binding. In the young animals, the resultant Hill coefficients derived from these analyses approached 1, while in the middle and old aged animals, the Hill coefficients deviated significantly from 1, indicating the possible existence of 2 or more receptor states with differential affinity for oxotremorine in the 2 older age groups. When carbamylcholine was used to inhibit 3H-QNB, these complex binding patterns were seen even in the young, since carbamylcholine induces conformational/orientational changes in the mAChR while oxotremorine does not.(ABSTRACT TRUNCATED AT 250 WORDS)
— id: 23629, year: 1985, vol: 6, page: 317, stat: Journal Article,

Prostanoid modulation (mediation?) of certain behavioral effects of ethanol
Segarnick DJ; Cordasco DM; Rotrosen J
1985 Jul;23(1):71-75, Pharmacology biochemistry & behavior
Prostaglandin E1 (PGE1) and prostanoid precursor fatty acids enhance the acute sedative effects of ethanol in mice, and reduce the intensity of withdrawal after chronic exposure to ethanol. Aspirin, and other inhibitors of prostanoid synthesis, attenuate ethanol's sedative effects, and interfere with the beneficial effects of prostanoid precursors (but not of PGE1 itself) in withdrawal. Neither aspirin nor indomethacin administered alone affect withdrawal behavior. In contrast, ethanol impairment of rotorod behavior is not affected by prostanoid precursors nor by aspirin. These findings support a role for prostanoids as modulators (? mediators) of certain direct effects of ethanol and a role for prostanoid deficiency in the pathogenesis of withdrawal behavior
— id: 23622, year: 1985, vol: 23, page: 71, stat: Journal Article,

Gamma-linolenic acid inhibits the development of the ethanol-induced fatty liver
Segarnick DJ; Mandio Cordasco D; Agura V; Cooper NS; Rotrosen J
1985 Mar;17(3):277-282, Prostglandins, leukotrienes & medicine
In the context of recent work showing numerous interactions between ethanol, essential fatty acids (EFA) and prostanoids, we have evaluated the effects of gamma-linolenic acid methyl ester (GLA 99%; 18:3, n-6), on hepatic pathology induced by ethanol in rats. Groups of animals were pair-fed an alcohol-containing liquid diet or an iso-caloric maltose-dextrin diet. Animals fed ethanol for ten days had markedly increased hepatic triglycerides and histological evidence of fatty liver. These effects were partially attenuated by administration of GLA during the period of ethanol administration
— id: 23627, year: 1985, vol: 17, page: 277, stat: Journal Article,

Precursor- and pool-dependent differential effects of ethanol on human platelet prostanoid synthesis
Segarnick DJ; Ryer H; Rotrosen J
1985 Apr 15;34(8):1343-1346, Biochemical pharmacology
— id: 23626, year: 1985, vol: 34, page: 1343, stat: Journal Article,

Olfactory dysfunction in Alzheimer's disease and Parkinson's disease
Serby M; Corwin J; Conrad P; Rotrosen J
1985 Jun;142(6):781-782, American journal of psychiatry
— id: 23623, year: 1985, vol: 142, page: 781, stat: Journal Article,

Olfaction in dementia
Serby M; Corwin J; Novatt A; Conrad P; Rotrosen J
1985 Aug;48(8):848-849, Journal of neurology neurosurgery & psychiatry
— id: 23621, year: 1985, vol: 48, page: 848, stat: Journal Article,

Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography
Wolkin A; Jaeger J; Brodie JD; Wolf AP; Fowler J; Rotrosen J; Gomez-Mont F; Cancro R
1985 May;142(5):564-571, American journal of psychiatry
Local cerebral metabolic rates were determined by positron emission tomography and the deoxyglucose method in a group of 10 chronic schizophrenic subjects before and after somatic treatment and in eight normal subjects. Before treatment, schizophrenic subjects had markedly lower absolute metabolic activity than did normal controls in both frontal and temporal regions and a trend toward relative hyperactivity in the basal ganglia area. After treatment, their metabolic rates approached those seen in normal subjects in nearly all regions except frontal. Persistence of diminished frontal metabolism was manifested as significant relative hypofrontality. These findings suggest specific loci of aberrant cerebral functioning in chronic schizophrenia and the utility of positron emission tomography in characterizing these abnormalities
— id: 23625, year: 1985, vol: 142, page: 564, stat: Journal Article,

Patterns of metabolic activity in the treatment of schizophrenia
Brodie JD; Christman DR; Corona JF; Fowler JS; Gomez-Mont F; Jaeger J; Micheels PA; Rotrosen J; Russell JA; Volkow ND; et al.
1984 ;15 Suppl(3-4):S166-S169, Annals of neurology
Six patients with chronic schizophrenia were studied with positron emission tomography (PET) before and after neuroleptic treatment, using fluorine-18-labeled fluorodeoxyglucose. After treatment, the mean whole-slice glucose metabolic rate at the level of the basal ganglia showed a 25% increase. However, patterns of frontal hypometabolism observed with the schizophrenic patients were not altered by medication. Pattern analysis using the fast Fourier transform was applied to a set of 422 images from a mixed group of normal, depressed, and schizophrenic subjects. Reconstruction of the images with low-frequency coefficients was excellent, reducing considerably the number of variables needed to characterize each image. Hierarchical cluster analysis categorized the transformed images according to anatomical level and subject group (patient versus control). The results suggest the utility of this procedure for the classification and characterization of metabolic PET images from psychiatric patients
— id: 23635, year: 1984, vol: 15 Suppl, page: S166, stat: Journal Article,

REGIONAL GLUCOSE-METABOLISM IN CHRONIC-SCHIZOPHRENIA
Brodie, JD; Wolkin, A; Wolfe, AP; Jaeger, J; Fowler, J; Rotrosen, J; Cancro, R
1984 ;2(3):226-226, International journal of psychophysiology
— id: 30978, year: 1984, vol: 2, page: 226, stat: Journal Article,

Cholecystokinin octapeptide in dementia
Serby M; Angrist B; Corwin J; Funari D; Sudilovsky A; Siekierski J; Peselow E; Rotrosen J
1984 Summer;20(3):546-547, Psychopharmacology bulletin
— id: 23637, year: 1984, vol: 20, page: 546, stat: Journal Article,

Side effects of scopolamine administration
Serby M; Corwin J; Jordan B; Novatt A; Rotrosen J
1984 Aug;141(8):1010-1010, American journal of psychiatry
— id: 23633, year: 1984, vol: 141, page: 1010, stat: Journal Article,

CSF somatostatin in Alzheimer's disease
Serby M; Richardson SB; Twente S; Siekierski J; Corwin J; Rotrosen J
1984 Fall;5(3):187-189, Neurobiology of aging
Studies have previously demonstrated low somatostatin levels in autopsy cortical tissue from Alzheimer's disease (AD) patients and low somatostatin levels in CSF obtained from subjects with dementia. We evaluated levels of this peptide in 21 non-depressed subjects, 10 with AD, 2 with Parkinson's disease (PD), and 9 with other neurological conditions. The AD patients had significantly lower mean CSF somatostatin than the 'other' neurological patients (14.6 +/- 1.5 S.E.M. versus 26.7 +/- 3.2 pg/ml, p less than 0.005). A demented PD subject had a level in the range of the AD group, while the non-demented PD patient had a value above this range. Thus, all 11 patients with AD or PD dementia, analogous disorders, had levels below 21.8 mg/ml, while 7 of the 10 remaining patients had values above 21.8 pg/ml. Age did not explain this finding
— id: 23636, year: 1984, vol: 5, page: 187, stat: Journal Article,

Murine lymphocytes lack clearly defined receptors for muscarinic and dopaminergic ligands
Wazer DE; Rotrosen J
1984 Dec;36(12):853-854, Journal of pharmacy & pharmacology
[3H]Quinuclidinyl benzilate and [3H]spiperone binding to murine lymphocytes is displaceable but differs from binding to brain receptor sites for these ligands: (1) binding to intact lymphocyte preparations was not saturable; (2) disruption of intact lymphocytes was associated with a marked loss of displaceable ligand binding; (3) drugs differentially displace these ligands in lymphocytes compared to brain. Displaceable binding was increased following incubation of lymphocytes under phospholipid methylating conditions; however, marked effects on cell viability and cell recovery make it difficult to interpret these binding changes. If dopaminergic and cholinergic receptors do exist on lymphocytes, their binding characteristics are profoundly different from comparable cns receptors
— id: 23632, year: 1984, vol: 36, page: 853, stat: Journal Article,

TRH test abnormalities in psychiatric disorders
Wolkin A; Peselow ED; Smith M; Lautin A; Kahn I; Rotrosen J
1984 Jun;6(3-4):273-281, Journal of affective disorders
Blunted responses to thyrotropin-releasing hormone (TRH) stimulation have been found consistently in depressed patients, and have been reported in other affective disorders as well. In a smaller number of schizophrenic subjects, TRH tests have generally been normal. Thus, it has been suggested that this test may have diagnostic utility in distinguishing schizophrenia from affective disorders. In the present study the TRH test was performed upon a sample of 51 subjects that included 17 schizophrenics in order to further study the diagnostic or symptom specificity of this endocrine test. Abnormal TRH tests were present in both schizophrenic and affectively disturbed patients. There were no correlations with ratings of depression or other aspects of psychopathology. Factors which may have previously obscured abnormal TRH tests in schizophrenia are discussed
— id: 23634, year: 1984, vol: 6, page: 273, stat: Journal Article,

Differential effects of tricyclic antidepressants on mean arterial pressure in a hypertensive patient
Adler L; Angrist B; Lautin A; Rotrosen J
1983 Apr;3(2):122-122, Journal of clinical psychopharmacology
— id: 23639, year: 1983, vol: 3, page: 122, stat: Journal Article,

Plasma cortisol values after dexamethasone in depressed inpatients
Peselow ED; Serby M; Wolkin A; Deutsch SI; Fricchione G; Rotrosen JP
1983 Feb;3(1):45-46, Journal of clinical psychopharmacology
— id: 23572, year: 1983, vol: 3, page: 45, stat: Journal Article,

LECITHIN AND PIRACETAM IN ALZHEIMERS-DISEASE
SERBY, M; CORWIN, J; ROTROSEN, J; FERRIS, SH; REISBERG, B; FRIEDMAN, E; SHERMAN, KA; JORDAN, B; BARTUS, R
1983 ;19(1):126-129, Psychopharmacology bulletin
— id: 40574, year: 1983, vol: 19, page: 126, stat: Journal Article,

Norepinephrine stimulation of phospholipid methylation in rat cortical synaptosomes: fact or artifact?
Wazer DE; Mandio Cordasco D; Segarnick DJ; Lippa AS; Meyerson LR; Benson D; Rotrosen J
1983 May 30;32(22):2535-2544, Life sciences
Synaptosomes from rat cerebral cortex incubated with 3H-S-adenosyl-L-methionine (3H-SAM) displayed an increase in chloroform- extractable tritium when norepinephrine was added to the reaction mixture. The products of this mixture were maximally generated from intact synaptosomes, only partially inhibited by propranolol, and not enhanced by exogenous phospholipids. Thin layer chromatographic analysis of these chloroform extracts in three solvent systems yielded large norepinephrine- stimulated peaks of radioactivity that did not consistently co-chromatograph with authentic methylated phospholipid standards: phosphatidylmonomethylethanolamine (PME), phosphatidyldimethylethanolamine (PDE), and phosphatidylcholine (PC). Further, attempts to identify these peaks of radioactivity using as standards several putative methylated products of varied chemical classes, failed to elucidate likely candidates. It appears that while norepinephrine markedly stimulates the amount of tritium extracted into the chloroform phase, careful and positive structural elucidation of formed products is required before it can be concluded that these are indeed methylated phospholipids
— id: 23638, year: 1983, vol: 32, page: 2535, stat: Journal Article,

Partial improvement in negative schizophrenic symptoms after amphetamine
Angrist B; Peselow E; Rubinstein M; Corwin J; Rotrosen J
1982 ;78(2):128-130, Psychopharmacology
In stable schizophrenic outpatients with predominantly 'defect state' symptomatology amphetamine caused a reduction in negative symptoms that was statistically significant but not complete (i.e. these symptoms remained clinically discernible). The possibility that dopaminergic hypofunction contributes some elements to the schizophrenic defect state is presented, along with some limited data compatible with this concept. These findings are compared to prior studies in recently hospitalized schizophrenic subjects, and discussed with respect to recent theoretical concepts regarding the role of dopamine in schizophrenic psychopathology
— id: 23641, year: 1982, vol: 78, page: 128, stat: Journal Article,

Red cell phospholipids in schizophrenia
Lautin A; Cordasco DM; Segarnick DJ; Wood L; Mason MF; Wolkin A; Rotrosen J
1982 Dec 27;31(26):3051-3056, Life sciences
Phospholipids in red blood cells (RBCs) of schizophrenics and controls were determined. Three different RBC preparations and two different extraction methods were used. Phospholipids were separated by thin layer chromatography and by high pressure liquid chromatography, and were quantified by phosphorus analysis and by ultraviolet absorption. Findings were consistent with values previously reported for normals. However, in contrast to recent reports of elevated phosphatidylserine levels in schizophrenics' RBCs, we observed no differences between populations
— id: 23640, year: 1982, vol: 31, page: 3051, stat: Journal Article,

Piracetam reduces alcohol withdrawal in mice without potentiating alcohol sedative effects
Serby M; Segarnick DJ; Cordasco DM; Rotrosen J
1982 Fall;6(4):520-522, Alcoholism: clinical & experimental research
— id: 23642, year: 1982, vol: 6, page: 520, stat: Journal Article,

The Benzamides : pharmacology, neurobiology, and clinical aspects
Stanley, Michael; Rotrosen, John
New York : Raven Press, c1982,
— id: 106, year: 1982, vol: , page: , stat: ,

The benzamides: evidence for action at dopamine receptors--shortcomings of current models
Wazer DE; Rotrosen J; Stanley M
1982 ;35(4):83-95, Advances in biochemical psychopharmacology
— id: 23643, year: 1982, vol: 35, page: 83, stat: Journal Article,

RELATIONSHIPS BETWEEN RESPONSES TO DOPAMINE AGONISTS PSYCHO PATHOLOGY NEUROLEPTIC TREATMENT RESPONSE AND NEED FOR NEUROLEPTIC MAINTENANCE IN SCHIZOPHRENIC SUBJECTS
ANGRIST B; PESELOW E; ROTROSEN J; GERSHON S
1981 ;35:P49-54, Advances in the biosciences
— id: 106740, year: 1981, vol: 35, page: P49, stat: Journal Article,

Human platelet phospholipid methylation
Cordasco DM; Segarnick DJ; Rotrosen J
1981 Nov 30;29(22):2299-2309, Life sciences
— id: 23644, year: 1981, vol: 29, page: 2299, stat: Journal Article,

Effect of lithium on glycine levels in patients with affective disorders
Deutsch SI; Peselow ED; Banay-Schwartz M; Gershon S; Virgilio J; Fieve RR; Rotrosen J
1981 May;138(5):683-684, American journal of psychiatry
— id: 23645, year: 1981, vol: 138, page: 683, stat: Journal Article,

DETERMINATION OF GLYCINE IN ULTRAFILTRATES OF PLASMA AND RBC LYSATES BY A DANSYLATION THIN-LAYER CHROMATOGRAPHIC METHOD
DEUTSCH, SI; PESELOW, ED; TRAFICANTE, LJ; VIRGILIO, J; STANLEY, M; ROTROSEN, J
1981 ;6(3):193-204, Research communications in psychology, psychiatry & behavior
— id: 40472, year: 1981, vol: 6, page: 193, stat: Journal Article,

THE EFFECT OF A NOVEL PSYCHOTROPIC AGENT, TREBENZOMINE, ON BRAIN AND PLATELET UPTAKE SYSTEMS
Friedman, E; Hallock, M; Rotrosen, J; Dallob, A
1981 ;6(4):289-294, Research communications in psychology, psychiatry & behavior
— id: 30326, year: 1981, vol: 6, page: 289, stat: Journal Article,

A double-blind comparison of trebenzomine and thioridazine in the treatment of schizophrenia
Georgotas A; Gerbino L; Jordan B; McCarthy M; Gershon S; Kleinberg D; Lautin A; Stanley M; Rotrosen J
1981 ;73(3):292-294, Psychopharmacology
Forty inpatient volunteers with diagnoses of schizophrenia were randomly assigned to treatment either with trebenzomine or thioridazine in a double-blind study of clinical antipsychotic efficacy following a 1-week placebo treatment. Psychopathology was rated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). There was a significant difference in therapeutic response to the two drugs in that psychopathology decreased significantly for the thioridazine group, but not for the trebenzomine group. Serum prolactin was elevated during treatment with thioridazine, but not with trebenzomine. Side effects were more frequently reported for the thioridazine group. These results fail to confirm previous reports of clinical antipsychotic efficacy for trebenzomine
— id: 23647, year: 1981, vol: 73, page: 292, stat: Journal Article,

Discrimination of functionally heterogeneous receptor subpopulations: antipsychotic and antidopaminergic properties of metoclopramide [proceedings]
Rotrosen J; Stanley M; Lautin A; Wazer D; Gershon S
1981 Jan;17(1):110-113, Psychopharmacology bulletin
— id: 23646, year: 1981, vol: 17, page: 110, stat: Journal Article,

SYMPOSIUM ON ALZHEIMERS-DISEASE
Serby, M; Corwin, J; Groher, M; Rotrosen, J
1981 ;2(3):233-234, Neurobiology of aging
— id: 30187, year: 1981, vol: 2, page: 233, stat: Journal Article,

Assessment of dopaminergic function in schizophrenia [proceedings]
Angrist B; Rotrosen J; Gershon S
1980 Jan;16(1):59-60, Psychopharmacology bulletin
— id: 23653, year: 1980, vol: 16, page: 59, stat: Journal Article,

Differential effects of amphetamine and neuroleptics on negative vs. positive symptoms in schizophrenia
Angrist B; Rotrosen J; Gershon S
1980 ;72(1):17-19, Psychopharmacology
Positive symptoms of schizophrenia were diminished by neuroleptics and increased by amphetamine and accounted for most of the change seen in the total Brief Psychiatric Rating Scale (BPRS). Negative symptoms in the same subjects were not affected by neuroleptics but increased after amphetamines to a degree that just attained statistical significance. This increase was due to one item (emotional withdrawal) of the negative symptom factor which responded to neuroleptics and amphetamines as did positive symptoms. These findings are discussed with respect to new ideas about the role of dopamine in schizophrenia
— id: 23654, year: 1980, vol: 72, page: 17, stat: Journal Article,

Responses to apomorphine, amphetamine, and neuroleptics in schizophrenic subjects
Angrist B; Rotrosen J; Gershon S
1980 Jan;67(1):31-38, Psychopharmacology
Twenty-one schizophrenic subjects, who had been neuroleptic-free, were tested for responsiveness to dopaminergic agonists: Apomorphine emesis threshold was determined and change in psychopathology after 0.5 mg/kg d-amphetamine orally was rated. The subjects' subsequent response to neuroleptic treatment were also determined. Sensitivity to apomorphine emesis was also determined in a nonschizophrenic control group. Apomorphine emesis threshold was not significantly different in the schizophrenic and control groups. Correlations were done between baseline psychopathology, apomorphine sensitivity, and changes in psychopathology after amphetamine and after neuroleptic treatment. On the Brief Psychiatric Rating Scale (BPRS), baseline psychopathology correlated with improvement after neuroleptics and, on the clinical global impressions (CGI), increase of psychopathology after amphetamine also correlated with improvement after neuroleptic treatment. An inverse correlation was found between several indices of sensitivity to amphetamine (psychopathology change) and emetic sensitivity to apomorphine. An examination of individual subjects' responses to amphetamine and, subsequently, neuroleptics, suggested that in the absence of significant clinical change after amphetamine a brisk therapeutic response to neuroleptics was rare
— id: 23656, year: 1980, vol: 67, page: 31, stat: Journal Article,

CHRONIC TREATMENT WITH METOCLOPRAMIDE INDUCES BEHAVIORAL SUPER- SENSITIVITY TO APOMORPHINE AND ENHANCES SPECIFIC BINDING OF H- 3-SPIROPERIDOL TO RAT STRIATA
Lautin, A; Wazer, D; Stanley, M; Rotrosen, J; Gershon, S
1980 ;27(4):305-316, Life sciences
— id: 27907, year: 1980, vol: 27, page: 305, stat: Journal Article,

Ethanol and prostaglandin E1: biochemical and behavioral interactions
Rotrosen J; Mandio D; Segarnick D; Traficante LJ; Gershon S
1980 Jun 2;26(22):1867-1876, Life sciences
— id: 23650, year: 1980, vol: 26, page: 1867, stat: Journal Article,

Prostaglandins, platelets, and schizophrenia
Rotrosen J; Miller AD; Mandio D; Traficante LJ; Gershon S
1980 Sep;37(9):1047-1054, Archives of general psychiatry
Prostaglandin (PG) E1 enhances formation of 3H-adenosine-3',5'-cyclic monophasphate (3H-cAMP) in platelets pulse-labeled with 3H-adenine. This response was assessed as an index of receptor sensitivity and of PG function. Prostagladin E1-stimulated 3H-cAMP accumulation in paltelets from schizophrenics was significantly reduced compared with control subjects. Platelet incorporation of 3H-adenine and basal 3H-cAMP accumulation. We discuss the results in terms of the possible role of PGs in the etiopathology of schizophrenia and derivative implications for treatment
— id: 23648, year: 1980, vol: 37, page: 1047, stat: Journal Article,

Experimental dystonia induced by quaternary-chlorpromazine
Rotrosen J; Stanley M; Kuhn C; Wazer D; Gershon S
1980 Aug;30(8):878-881, Neurology
When quaternary-chlorpromazine (Q-CPZ) was administered intraventricularly (ICV) to rats, it induced a lateralized dystonic reaction, which progressed to head-to-tail barrel rolling. The syndrome persisted for approximately 10 minutes, was not antagonized by pretreatment with drugs used to treat extrapyramidal movement disorders, and could not be mimicked by ICV administration of dopamine antagonists. Unlike known dopamine antagonists, Q-CPZ does not alter dopamine turnover, cause prolactin release in vivo, or bind to dopamine/neuroleptic receptors in vitro. These data suggest that Q-CPZ differs substantially from CPZ in pharmacologic action, and that it elicits a behavioral syndrome of potential use for studying dystonias
— id: 23649, year: 1980, vol: 30, page: 878, stat: Journal Article,

Metoclopramide: antipsychotic efficacy of a drug lacking potency in receptor models
Stanley M; Lautin A; Rotrosen J; Gershon S; Kleinberg D
1980 ;71(3):219-225, Psychopharmacology
Metoclopramide is a substituted benzamide derivative, structurally similar to procainamide and sulpiride. In behavioral, biochemical, and neuroendocrine tests it displays classic neuroleptic dopamine (DA) antagonist properties; in contrast to other DA antagonists, it lacks potency in currently used DA receptor models. In clinical studies using low doses or dubious measures, it was considered not to be efficacious as an antipsychotic. We now find that it indeed has a clinical profile similar to known neuroleptics when used in a dose range predicted from animal models. The findings raise questions regarding the validity and universality of several predictive models, as well as hypotheses purporting to explain molecular mechanisms of action of neuroleptic agents. The drug's inactivity in receptor models suggests that an as yet unidentified DA receptor subpopulation may be important as the mediator of many DA dependent neurobiologic phenomena
— id: 23655, year: 1980, vol: 71, page: 219, stat: Journal Article,

Enkephalin inactivation by N-terminal tyrosine cleavage: purification and partial characterization of a highly specific enzyme from human brain
Traficante LJ; Rotrosen J; Siekierski J; Tracer H; Gershon S
1980 May 19;26(20):1697-1706, Life sciences
— id: 23652, year: 1980, vol: 26, page: 1697, stat: Journal Article,

Antibiotics as inhibitors of enkephalin degradation by human brain
Traficante LJ; Siekierski J; Rotrosen J; Gershon S
1980 Jun;12(6):575-580, Pharmacology research communications
— id: 23651, year: 1980, vol: 12, page: 575, stat: Journal Article,

Behavioral and neuroendocrine effects of low dose ET-495: antagonism by haloperidol
Angrist B; Ain M; Rotrosen J; Gershon S; Halpern FS; Sachar EJ
1979 ;44(4):249-262, Journal of neural transmission
Low doses of the dopamine agonist ET-495 were administered to nonpsychotic volunteer subjects by slow intravenous infusion, followed by a bolus of 1.5--2.5 mg haloperidol. ET-495 caused progressive dysphoria and sedation (in some cases, light sleep), effects believed to be mediated by dopaminergic inhibition. However, ET-495 also elevated growth hormone and suppressed prolactin, typical responses to dopamine agonist activity. Haloperidol reversed both the sedation and prolactin suppression induced by ET-495. These findings suggest: (1) that the sedation and hormonal responses were produced by stimulation of dopamine receptors; (2) that neurotransmitter systems mediating behavioral and neuroendocrine regulation may have differential neuropharmacological characteristics
— id: 23660, year: 1979, vol: 44, page: 249, stat: Journal Article,

Neuroendocrine effects of apomorphine: characterization of response patterns and application to schizophrenia research
Rotrosen J; Angrist B; Gershon S; Paquin J; Branchey L; Oleshansky M; Halpern F; Sachar EJ
1979 Nov;135(8153):444-456, British journal of psychiatry
Apomorphine, a direct-acting dopamine agonist, stimulates release of growth hormone (hGH) and suppresses release of prolactin (PRL) from the anterior pituitary. Previous studies comparing the magnitude of these responses in schizophrenics and controls suggest that many acute (and some chronic) schizophrenics have exaggerated hGH responses; many chronic schizophrenics (and patients with tardive dyskinesia) have blunted hGH responses to apomorphine, and possibly blunted PRL responses. The present studies extend and confirm these findings in chronic schizophrenics; in addition, several studies were undertaken to further characterize these apomorphine-induced endocrine responses. Studies in which apomorphine was given on 2 or 3 separate occasions to each of five subjects indicate that the hGH response is a highly reproducible individual index, but PRL suppression is a less satisfactory measure. hGH responses to apomorphine were consistently antagonized by pretreatment with haloperidol, supporting the concept that the hGH-releasing effect of apomorphine is mediated by its action on dopamine receptors. Cyproheptadine pretreatment was associated with erratic increases or decreases in the hGH response to apomorphine, but did not alter PRL levels or apomorphine-induced PRL suppression. The relationship of these findings to biological hypotheses of schizophrenia and to neuroleptic-induced receptor changes is discussed
— id: 23658, year: 1979, vol: 135, page: 444, stat: Journal Article,

Tardive dyskinesia and metoclopramide
Stanley M; Rotrosen J; Lautin A; Wazer D; Gershon S
1979 Dec 1;2(8153):1190-1190, Lancet
— id: 23657, year: 1979, vol: 2, page: 1190, stat: Journal Article,

Atypical antidopaminergic properties of CI-686: a potential antipsychotic agent
Stanley M; Rotrosen J; Sculerati N; Gershon S; Kuhn C; Cohen BM
1979 ;66(1):23-27, Psychopharmacology
The effects of the antipsychotic/antidepressant drug CI-686 on apomorphine- and amphetamine-induced stereotypies, dopamine metabolism, neuroleptic binding, and serum prolactin levels were determined. CI-686 displayed profiles of activity in each of these systems that differs markedly from those of other antipsychotics. CI-686's unique preclinical profile suggests a mechanism of action other than dopamine antagonism which could have implications regarding current thinking on the pathophysiology of schizophrenia
— id: 23661, year: 1979, vol: 66, page: 23, stat: Journal Article,

Rapid in vitro sulfoxidation of chlorpromazine by human blood: inhibition by an endogenous plasma protein factor
Traficante LJ; Sakalis G; Siekierski J; Rotrosen J; Gershon S
1979 Jan 22;24(4):337-345, Life sciences
— id: 23659, year: 1979, vol: 24, page: 337, stat: Journal Article,

PURIFICATION AND PARTIAL CHARACTERIZATION OF A HUMAN-BRAIN ENZYME - SPECIFICITY FOR MET-ENKEPHALIN
TRAFICANTE, LJ; ROTROSEN, J; SIEKIERSKI, J; TRACER, H; GERSHON, S
1979 ;7(11):561-561, IRCS medical science. Biochemistry
— id: 50172, year: 1979, vol: 7, page: 561, stat: Journal Article,

Suppression of prolactin by dopamine agonists in schizophrenics and controls
Rotrosen J; Angrist B; Clark C; Gershon S; Halpers FS; Sachar EJ
1978 Aug;135(8):949-951, American journal of psychiatry
Prolactin levels were determined in plasma samples obtained before and after administration of apomorphine or L-dopa to otherwise unmedicated chronic schizophrenic patients or control subjects. Basal prolactin levels did not differ in these two groups. Suppression of prolactin levels after each dopamine agonist was highly significant. Suppression in schizophrenics was slightly less than in controls following apomorphine and slightly greater following L-dopa. The authors discuss the implications of these findings as well as the limitations of the prolactin regulatory system as an index of dopamine agonist sensitivity
— id: 23665, year: 1978, vol: 135, page: 949, stat: Journal Article,

Neuroendocrine studies with dopamine agonists in schizophrenia
Rotrosen J; Angrist B; Paquin J
1978 Jan;14(1):14-17, Psychopharmacology bulletin
— id: 23667, year: 1978, vol: 14, page: 14, stat: Journal Article,

Thiethylperazine; clinical antipsychotic efficacy and correlation with potency in predictive systems
Rotrosen J; Angrist BM; Gershon S; Aronson M; Gruen P; Sachar EJ; Denning RK; Matthysse S; Stanley M; Wilk S
1978 Sep;35(9):1112-1118, Archives of general psychiatry
A one-to-one relationship between clinical antipsychotic potency and pharmacologic dopaminergic antagonism is implicit in the dopamine hypothesis of neuroleptic action. Thiethylperazine maleate, a classical antiemetic phenothiazine, displays dopaminergic antagonism in behavioral, neurochemical, and neuroendocrine systems, but is paradoxical insofar as it is thought not to possess clinical neuroleptic activity. In three tests of dopaminergic antagonism--elevation of levels of CSF homovanillic acid in monkeys, striatal dihydroxyphenylacetic acid in rats, and prolactin in man--as well as in a clinical trial of neuroleptic efficacy in schizophrenics, thiethylperazine was fully active and approximately three times as potent as chlorpromazine. Differences in efficacy between this and earlier clinical studies can be accounted for on the basis of dosage
— id: 23664, year: 1978, vol: 35, page: 1112, stat: Journal Article,

Reduced PGE1 stimulated 3H-cAMP accumulation in platelets from schizophrenics
Rotrosen J; Miller AD; Mandio D; Traficante LJ; Gershon S
1978 Nov 13;23(20):1989-1996, Life sciences
— id: 23662, year: 1978, vol: 23, page: 1989, stat: Journal Article,

Effects of plant lectins on cation-activated brain ATPases
Rotrosen J; Traficante LJ; Covner B; Basuk P; Gershon S
1978 Sep 25;23(12):1241-1247, Life sciences
— id: 23663, year: 1978, vol: 23, page: 1241, stat: Journal Article,

Effect of lithium on the membrane-bound magnesium-dependent ATPase of mouse neuroblastoma cells
Shenkman L; Traficante LJ; Rotrosen J; Gershon S
1978 ;2(1):65-72, Communications in psychopharmacology
— id: 23668, year: 1978, vol: 2, page: 65, stat: Journal Article,

Stimulation of the membrane-bound, magnesium-dependent adenosine triphosphatase of mouse neuroblastoma by concanavalin A and wheat germ agglutinin
Traficante LJ; Shenkman L; Rotrosen J; Gershon S
1978 Mar;22(12):1059-1066, Life sciences
— id: 23666, year: 1978, vol: 22, page: 1059, stat: Journal Article,

Dopaminergic agonist properties of ephedrine--theoretical implications
Angrist B; Rotrosen J; Kleinberg D; Merriam V; Gershon S
1977 Dec 19;55(2):115-120, Psychopharmacology
Reports of ephedrine-induced psychoses resembling amphetamine psychosis prompted studies of this classic sympathomimetic agent in systems that indicate central dopaminergic actions. Ephedrine induced dose-related stereotyped behavior in rats. This behavior was antagonized by haloperidol, but not by alpha- or beta-adrenergic blockers. Pretreatment with AMPT, but not reserpine, attenuated the stereotypy induced by ephedrine under one of two sets of conditions. Consistent prolactin suppression in humans was not seen. These findings are discussed in the context of clinical and pharmacologic data regarding other dopamine agonist drugs (the central nervous system stimulants, apomorphine, ET 495). These data suggest the possibility that synergistic noradrenergic and dopaminergic facilitation may be important in the induction of the stimulant psychoses
— id: 23669, year: 1977, vol: 55, page: 115, stat: Journal Article,

Neuroendocrine assessment of dopaminergic activity in schizophrenia
Rotrosen, J; Angrist, B M; Gershon, S; Sachar, E J; Halpern, F S
1977 ;16(2):649-53, Advances in biochemical psychopharmacology
— id: 106738, year: 1977, vol: 16, page: 649, stat: Journal Article,

A morphanthridine derivative in schizophrenic patients -- lack of extrapyramidal symptoms
Angrist B; Rotrosen J; Aronson M; Gershon S
1976 Jul;20(1):94-98, Current therapeutic research
— id: 23671, year: 1976, vol: 20, page: 94, stat: Journal Article,

Dopamine receptor alteration in schizophrenia: neuroendocrine evidence
Rotrosen J; Angrist BM; Gershon S; Sachar EJ; Halpern FS
1976 Dec 21;51(1):1-7, Psychopharmacology
Growth hormone (hGH) responses to centrally acting dopamine agonists were used as indices of CNS dopaminergic function in order to test hypotheses implicating dopaminergic alteration in the etiopathology of schizophrenia. Apomorphine, a direct acting dopamine receptor agonist, and L-Dopa, an indirect agonist dependent upon presynaptic conversion to dopamine for its action, both elicited elevations in plasma hGH in most young male schizophrenic- and control-subjects. A highly significant difference was seen between the distribution of hGH responses to apomorphine for schizophrenics and that for controls. Unusually high hGH response to apomorphine was seen in schizophrenics who subsequently failed to respond to neuroleptic therapy; intermediate hGH response was seen in controls; and low hGH response was seen in subsequent neuroleptic responders; differences in hGH response were statistically significant for all intergroup comparisons. No such differences were seen between responses of individuals to L-Dopa and to apomorphine. The findings suggest that the variability of hGH response to apomorphine is a reflection of dopamine receptor sensitivity, and that this variability may be an index of non-endocrine related dopaminergic sensitivity. They are consistent with hypotheses relating schizophrenia to alteration in dopamine receptors, although the type of receptor and the direction of alteration may be complex
— id: 23670, year: 1976, vol: 51, page: 1, stat: Journal Article,

Effects of acute cocaine treatment on the turnover of 5-hydroxytryptamine in the rat brain
Friedman E; Gershon S; Rotrosen J
1975 May;54(1):61-64, British journal of pharmacology
1. The effects of cocaine (20 mg/kg s.c.) on 5-hydroxytryptamine (5-HT) turnover were examined in rats. 2. In vivo cocaine administration resulted in decreased turnover of 5-HT, as indicated by the decreased accumulation of 5-HT after pargyline administration and the decreased accumulation of 5-hydroxyindoleacetic acid (5-HIAA) following probenecid injection. 3. A time-related decrease in 5-HIAA concentrations and a small fall in 5-HT concentrations in the whole brain were observed following the acute administration of cocaine hydrochloride (20 mg/kg). Tryptophan levels were found to be slightly decreased in the brain. 4. Enhanced reactivity, but neither stereotypy nor hyperthermia, was observed following cocaine injection (20 mg/kg). 5. It is concluded that cocaine inhibits the turnover of brain 5-HT and that this action of cocaine may be responsible for the differences in a number of pharmacological effects between cocaine and amphetamine
— id: 23674, year: 1975, vol: 54, page: 61, stat: Journal Article,

Enhancement of reserpine-elicited dopaminergic supersensitivity by repeated treatment with apomorphine and alpha-methyl-p-tyrosine
Friedman E; Rotrosen J; Gurland M; Lambert GA; Gershon S
1975 Sep 15;17(6):867-873, Life sciences
— id: 23672, year: 1975, vol: 17, page: 867, stat: Journal Article,

Striatal adenylate cyclase activity following reserpine and chronic chlorpromazine administration in rats
Rotrosen J; Friedman E; Gershon S
1975 Aug 15;17(4):563-568, Life sciences
— id: 23673, year: 1975, vol: 17, page: 563, stat: Journal Article,

The search for the dopamine receptor: tribulations
Rotrosen J; Friedman E; Gershon S
1975 ;1(2):229-237, Psychopharmacology communications
In an attempt to identify specific binding to dopamine receptors the binding of 3H-pimozide to preparations of brain and to an artificial cellulose membrane was examined. Binding occurred rapidly, was pH and temperature dependent, and was displaceable by other neuroleptics. Displaceable binding was saturable at 5 X 10(-8) M pimozide. A weak correlation between IC50's for displacement of binding by drugs and their clinical potencies was observed. Displaceable binding of 3H-pimozide in different brain areas did not correlate with dopamine levels. The similarity of binding properties to brain and to artificial membrane suggests that these effects are a function of the physical-chemical properties of these drugs, and that these properties may be related to their clinical effect
— id: 23675, year: 1975, vol: 1, page: 229, stat: Journal Article,

Assessment of tolerance to the hallucinogenic effects of DOM
Angrist B; Rotrosen J; Gershon S
1974 Apr 23;36(3):203-207, Psychopharmacology
— id: 23676, year: 1974, vol: 36, page: 203, stat: Journal Article,

A neuropsychopharmacological study of phenmetrazine in several animal species
Wallach MB; Rotrosen J; Gershon S
1973 Jun;12(6):541-548, Neuropharmacology
— id: 23677, year: 1973, vol: 12, page: 541, stat: Journal Article,

Absence of serotonergic influence on apomorphine-induced stereotypy
Rotrosen J; Angrist BM; Wallach MB; Gershon S
1972 Oct;20(1):133-135, European journal of pharmacology
— id: 23678, year: 1972, vol: 20, page: 133, stat: Journal Article,

Antagonism of apomorphine-induced sterotypy and emesis in dogs by thioridazine, haloperidol, and pimozide
Rotrosen J; Wallach MB; Angrist B; Gershon S
1972 ;26(2):185-194, Psychopharmacology
— id: 23679, year: 1972, vol: 26, page: 185, stat: Journal Article,