Glenn S Hirsch, M.D.

The possible role of the kynurenine pathway in adolescent depression with melancholic features
Gabbay, Vilma; Klein, Rachel G; Katz, Yisrael; Mendoza, Sandra; Guttman, Leah E; Alonso, Carmen M; Babb, James S; Hirsch, Glenn S; Liebes, Leonard
2010 Aug;51(8):935-943, Journal of child psychology & psychiatry & allied disciplines
BACKGROUND: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. METHODS: Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be >or= 6 weeks and Children's Depression Rating Scale-Revised (CDRS-R) scores were >or= 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher's protected least significant difference was used for multiple comparisons. RESULTS: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R. CONCLUSIONS: Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome
— id: 111344, year: 2010, vol: 51, page: 935, stat: Journal Article,

Immune system dysregulation in adolescent major depressive disorder
Gabbay, Vilma; Klein, Rachel G; Alonso, Carmen M; Babb, James S; Nishawala, Melissa; De Jesus, Georgette; Hirsch, Glenn S; Hottinger-Blanc, Pauline M Z; Gonzalez, Charles J
2009 May;115(1-2):177-182, Journal of affective disorders
BACKGROUND: A large body of evidence suggests that immune system dysregulation is associated with Major Depressive Disorder (MDD) in adults. This study extends this work to adolescent MDD to examine the hypotheses of immune system dysregulation in adolescents with MDD, as manifested by significantly: (i) elevated plasma levels of cytokines (interferon [IFN]-gamma, tumor necrosis factor-alpha, interleukin [IL]-6, IL-1beta, and IL-4); and (ii) Th1/Th2 cytokine imbalance shifted toward Th1 as indexed by increased IFN-gamma/IL-4. METHOD: Thirty adolescents with MDD (19 females; 13 medication-free/naive; ages 12-19) of at least 6 weeks duration and a minimum severity score of 40 on the Children's Depression Rating Scale-Revised, and 15 healthy comparisons (8 females), group-matched for age, were enrolled. Plasma cytokines were examined using enzyme-linked immunosorbent assay. Mann-Whitney test was used to compare subjects with MDD and controls. RESULTS: Adolescents with MDD had significantly elevated plasma IFN-gamma levels (3.38+/-11.8 pg/ml versus 0.37+/-0.64 pg/ml; p<0.003), and IFN-gamma/IL-4 ratio (16.6+/-56.5 versus 1.76+/-2.28; p=0.007). A trend for IL-6 to be elevated in the MDD group was also observed (1.52+/-2.88 pg/ml versus 0.49+/-0.90 pg/ml; p=0.09). Importantly, findings remained evident when medicated subjects were excluded. CONCLUSIONS: Findings suggest that immune system dysregulation may be associated with adolescent MDD, with an imbalance of Th1/Th2 shifted toward Th1, as documented in adult MDD. Larger studies with medication-free adolescents should follow
— id: 93920, year: 2009, vol: 115, page: 177, stat: Journal Article,

The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up
March, John; Silva, Susan; Curry, John; Wells, Karen; Fairbank, John; Burns, Barbara; Domino, Marisa; Vitiello, Benedetto; Severe, Joanne; Riedal, Karyn; Goldman, Marguerita; Feeny, Norah; Findling, Robert; Stull, Sheridan; Baab, Susan; Weller, Elizabeth B; Robbins, Michele; Weller, Ronald A; Jessani, Naushad; Waslick, Bruce; Sweeney, Michael; Dublin, Randi; Walkup, John; Ginsburg, Golda; Kastelic, Elizabeth; Koo, Hyung; Kratochvil, Christopher; May, Diane; LaGrone, Randy; Vaughan, Brigette; Albano, Anne Marie; Hirsch, Glenn S; Podniesinki, Elizabeth; Chu, Angela; Reincecke, Mark; Leventhal, Bennett; Rogers, Gregory; Jacobs, Rachel; Pathak, Sanjeev; Wells, Jennifer; Lavanier, Sarah A; Danielyan, Arman; Rohde, Paul; Simons, Anne; Grimm, James; Frank, Stephanie; Emslie, Graham; Kennard, Beth; Hughes, Carroll; Mayes, Taryn L; Rosenberg, David; Benazon, Nili; Butkus, Michael; Bartoi, Marla
2009 Oct;166(10):1141-1149, American journal of psychiatry
OBJECTIVE: The Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and their combination in adolescents with major depressive disorder. The authors report effectiveness outcomes across a 1-year naturalistic follow-up period. METHOD: The randomized, controlled trial was conducted in 13 academic and community sites in the United States. Stages I, II, and III consisted of 12, 6, and 18 weeks of acute, consolidation, and continuation treatment, respectively. Following discontinuation of TADS treatments at the end of stage III, stage IV consisted of 1 year of naturalistic follow-up. The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder. No TADS treatment was provided during the follow-up period; treatment was available in the community. The primary dependent measures, rated by an independent evaluator blind to treatment status, were the total score on the Children's Depression Rating Scale-Revised and the rate of response, defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure. RESULTS: Sixty-six percent of the eligible subjects participated in at least one stage IV assessment. The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality. CONCLUSIONS: In contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up
— id: 149997, year: 2009, vol: 166, page: 1141, stat: Journal Article,

Bored at school: Multimodal treatment of Tourette's disorder
Hirsch, Glenn S; Koplewicz, Harold S
DSM-IV-TRReg Washington, DC, US: American Psychiatric Publishing, Inc., 2006,
This chapter presents the case of a young boy with Tourette's disorder. History is first, including presenting symptoms, course of illness, and presenting mental status. Next is diagnosis. Finally, treatment is discussed, including recommendations, treatment course, and a concluding discussion
— id: 4774, year: 2006, vol: , page: 3, stat: Chapter,

Epidemiological Aspects of PTSD in Children and Adolescents
Gabbay, Vilma; Oatis, Melvin D; Silva, Raul R; Hirsch, Glenn S
Posttraumatic stress disorders in children and adolescents: Handbook New York, NY, US: W W Norton & Co., 2004,
(from the chapter) With the ever increasing exposure of children and adolescents to the hostilities of school shootings, terrorist attacks, threats of war, destruction of public property, suicide bombings and natural disasters, posttraumatic stress disorder (PTSD) has become recognized as a major public health problem. The widespread coverage of the September llth, 2001, terrorist attacks on the United States has underscored the importance of epidemiological research regarding PTSD. In this chapter, important aspects involving the epidemiology of PTSD in children and adolescents will be discussed. Current research data regarding prevalence of PTSD in the general population will be presented as well as the relation to specific traumatic experiences in the realms of child maltreatment, disasters, car accidents, war zones, medical illness, and violence.
— id: 3788, year: 2004, vol: , page: 1, stat: Chapter,

ADHD drug therapy
Hirsch GS
2001 May;18(3):35-38, School nurse news
— id: 26851, year: 2001, vol: 18, page: 35, stat: Journal Article,

Tardive dyskinesia and pregnancy and delivery complications
El-DeFrawi, Mohamed H; Hirsch, Glenn; Jurkowicz, Abel; Craig, Thomas J
1996 Spring;26(3):151-157, Child psychiatry & human development
Reports on a pilot study that examined the relationship between presence of treatment-emergent tardive dyskinesia (TD) and history of pregnancy and delivery complications in a sample of 61 child and adolescent psychiatric inpatients. Ss were assessed over a 7-mo period using the Abnormal Involuntary Movement Scale for the presence of treatment-emergent TD on admission and after 2 and 4 wks of neuroleptic treatment. Charts and records were also reviewed to obtain clinical data. Results show that 20% of the sample received a diagnosis of treatment-emergent TD. Neonatal and perinatal complications were significantly associated with the presence of treatment-emergent TD while there was no significant association with developmental delay or neurological events. Findings suggest that pregnancy and delivery complications may increase the risk of the development of treatment-emergent TD.
— id: 24897, year: 1996, vol: 26, page: 151, stat: Journal Article,

The somatizing disorders: Somatoform disorders, factitious disorders, and malingering
Williams, Daniel T; Hirsch, Glenn
Handbook of clinical assessment of children and adolescents New York, NY, US: New York University Press. xxvii, 1170pp,
(from the chapter) it is an important responsibility of the well-trained child and adolescent psychiatrist to be sensitive and informed about the complexities of this group of disorders [somatizing disorders], so that appropriate evaluation and intervention at an early stage can minimize or prevent a progression toward chronic somatization clinical entities / somatoform disorders / conversion disorder / idiopathic pain disorder / somatization disorder / hypochondriasis / factitious disorders / munchausen syndrome by proxy / malingering epidemiology / differential diagnosis / etiology / diagnosis / treatment
— id: 2672, year: 1988, vol: , page: 743, stat: Chapter,