Melanie E Schwarz, M.D.

Tryptophan depletion and emotional processing in healthy volunteers at high risk for depression
Feder, Adriana; Skipper, Jamie; Blair, James R; Buchholz, Katherine; Mathew, Sanjay J; Schwarz, Markus; Doucette, John T; Alonso, Angelique; Collins, Katherine A; Neumeister, Alexander; Charney, Dennis S
2011 Apr 15;69(8):804-807, Biological psychiatry
BACKGROUND: Studies in depressed patients have demonstrated the presence of emotional bias toward negative stimuli, as well as dysregulated brain serotonin function. The present study compared the effects of acute tryptophan depletion (ATD) on both an emotional processing and a planning task in never-depressed healthy volunteers at high and low familial risk for depression. METHODS: Young adults with no personal psychiatric history were stratified into two groups based on family history (n = 25). Participants were enrolled in a randomized, double-blind, placebo-controlled crossover ATD study and completed the affective go/no-go and Tower of London tasks once during each condition. RESULTS: There was a significant treatment by valence by group interaction on the affective go/no-go, driven primarily by a greater frequency of inappropriate responses to sad than to happy distracters in the high-risk group during ATD. No group differences were observed on the Tower of London. CONCLUSIONS: Asymptomatic individuals at high familial risk for depression showed abnormalities in emotional processing while undergoing experimentally induced tryptophan depletion. These findings support emotional processing disturbances as potential trait-level abnormalities associated with the risk of mood disorder
— id: 146312, year: 2011, vol: 69, page: 804, stat: Journal Article,

Differential effects of 5-HTTLPR genotypes on the behavioral and neural responses to tryptophan depletion in patients with major depression and controls
Neumeister, Alexander; Hu, Xian-Zhang; Luckenbaugh, David A; Schwarz, Markus; Nugent, Allison C; Bonne, Omer; Herscovitch, Peter; Goldman, David; Drevets, Wayne C; Charney, Dennis S
2006 Sep;63(9):978-986, Archives of general psychiatry
CONTEXT: Tryptophan depletion (TD) is a model used to study the contribution of reduced serotonin transmission to the pathogenesis of major depressive disorder (MDD). Recent studies have not sufficiently addressed the relative contribution of a functional-length triallelic polymorphism in the promoter of the serotonin transporter, 5-HTTLPR, to the behavioral and neural responses to TD in individuals with remitted MDD (rMDD) and controls. OBJECTIVE: To determine the role of 5-HTTLPR on the behavioral and neural responses to TD in medication-free patients with rMDD and individually matched controls. DESIGN: Participants were stratified according to diagnosis and 5-HTTLPR genotypes and underwent TD on one test day and sham depletion on the other test day in a prospective, double-blind, randomized order. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven medication-free patients with rMDD (18 women and 9 men) and 26 controls (17 women and 9 men). INTERVENTIONS: Tryptophan depletion was induced by administration of capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing lactose. Fludeoxyglucose F 18 positron emission tomography was performed 6 hours after TD. Magnetic resonance images were obtained for each participant. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral metabolic rates for glucose and measures of depression using the Hamilton Depression Rating Scale. RESULTS: Behavioral responses to TD are affected by 5-HTTLPR in patients with rMDD and controls. A direct effect of 5-HTTLPR on the regulation of regional cerebral metabolic rates for glucose was identified in patients with rMDD for the amygdala, hippocampus, and subgenual anterior cingulate cortex. CONCLUSIONS: Variations in 5-HTTLPR modulate the sensitivity of patients with rMDD and controls to the behavioral effects of TD. In patients with rMDD, variations in triallelic 5-HTTLPR have a direct effect on regulation of regional cerebral metabolic rates for glucose in a corticolimbic circuit that has been implicated in rMDD
— id: 146331, year: 2006, vol: 63, page: 978, stat: Journal Article,

The Patient With Cardiovascular Disease
Wyszynski, Antoinette Ambrosino; Schwarz, Melanie; Rubenstein, Bruce; Rodack, Victor B; Santos, Manuel
Manual of psychiatric care for the medically ill Washington, DC, US: American Psychiatric Publishing, Inc., 2005,
Chapter discusses the diagnostic and management dilemmas that complicate the accurate diagnosis of depression in medical patients, specifically in those patients with cardiac disorders. Among the difficulties noted are: neuropsychiatric effects of cardiac medications, and psychological symptoms that overlap those occurring in patients with pacemakers or defibrillators. Although this chapter concentrates on medication management, cardiac rehabilitation programs have become the key to secondary prevention after myocardial events, reducing mortality and improving exercise tolerance, functional capacity, blood pressure, and symptoms of angina and dyspnea as well as psychosocial functioning (Wenger et al. 1995). Components of most rehabilitation programs include exercise training, risk factor modification, education, medical surveillance, vocational rehabilitation, and psychological counseling (McGee et al. 1999). Psychopathology and gender difference may affect how cardiac rehabilitation is utilized (Grace et al. 2002a, 2002b).
— id: 3592, year: 2005, vol: , page: 49, stat: Chapter,

Neural and behavioral responses to tryptophan depletion in unmedicated patients with remitted major depressive disorder and controls
Neumeister, Alexander; Nugent, Allison C; Waldeck, Tracy; Geraci, Marilla; Schwarz, Markus; Bonne, Omer; Bain, Earle E; Luckenbaugh, David A; Herscovitch, Peter; Charney, Dennis S; Drevets, Wayne C
2004 Aug;61(8):765-773, Archives of general psychiatry
CONTEXT: An instructive paradigm for investigating the relationship between brain serotonin function and major depressive disorder (MDD) is the response to tryptophan depletion (TD) induced by oral loading with all essential amino acids except the serotonin precursor tryptophan. OBJECTIVE: To determine whether serotonin dysfunction represents a trait abnormality in MDD in the context of specific neural circuitry abnormalities involved in the pathogenesis of MDD. DESIGN: Randomized double-blind crossover study. SETTING: Outpatient clinic. PARTICIPANTS: Twenty-seven medication-free patients with remitted MDD (18 women and 9 men; mean +/- SD age, 39.8 +/- 12.7 years) and 19 controls (10 women and 9 men; mean +/- SD age, 34.4 +/- 11.5 years). INTERVENTIONS: We induced TD by administering capsules containing an amino acid mixture without tryptophan. Sham depletion used identical capsules containing hydrous lactose. Fluorodeoxyglucose F 18 positron emission tomography studies were performed 6 hours after TD. Magnetic resonance images were obtained for all participants. MAIN OUTCOME MEASURES: Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of sham depletion and TD. Behavioral assessments used a modified (24-item) version of the Hamilton Depression Rating Scale. RESULTS: Tryptophan depletion induced a transient return of depressive symptoms in patients with remitted MDD but not in controls (P<.001). Compared with sham depletion, TD was associated with an increase in regional cerebral glucose utilization in the orbitofrontal cortex, medial thalamus, anterior and posterior cingulate cortices, and ventral striatum in patients with remitted MDD but not in controls. CONCLUSION: The pattern of TD-induced regional cerebral glucose utilization changes in patients with remitted MDD suggests that TD unmasks a disease-specific, serotonin system-related trait dysfunction and identifies a circuit that probably plays a key role in the pathogenesis of MDD
— id: 146342, year: 2004, vol: 61, page: 765, stat: Journal Article,

Experimental evaluation of an altered tryptophan metabolism in fibromyalgia
Schwarz, Markus J; Offenbaecher, Martin; Neumeister, Alexander; Ackenheil, Manfred
2003 ;527:265-275, Advances in experimental medicine & biology
Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesised underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and Interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism and IL-6 production. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia
— id: 146351, year: 2003, vol: 527, page: 265, stat: Journal Article,

Effects of tryptophan depletion and catecholamine depletion on immune parameters in patients with seasonal affective disorder in remission with light therapy
Stastny, Jurgen; Konstantinidis, Anastasios; Schwarz, Markus J; Rosenthal, Norman E; Vitouch, Oliver; Kasper, Siegfried; Neumeister, Alexander
2003 Feb 15;53(4):332-337, Biological psychiatry
BACKGROUND: Altered immunologic parameters are found in symptomatic depressed patients relative to remitted depressed patients and healthy controls. We investigated whether tryptophan depletion and catecholamine depletion induce alterations in immunologic parameters in patients with seasonal affective disorder remitted on light therapy, and whether these changes are associated with changes in mood. METHODS: Remitted patients with seasonal affective disorder underwent tryptophan depletion, catecholamine depletion, and sham depletion in a prospective randomized, double-blind crossover design. Measures of depression, plasma levels of tryptophan and catecholamine metabolites, and plasma levels of cytokines (sIL-4, IL-6, neopterin, sTNF-R1 and sTNF-R2) were obtained at baseline, and 7, 24, and 30 hours after monoamine depletion. RESULTS: Tryptophan depletion decreased plasma total and free tryptophan levels; catecholamine depletion decreased plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels. Tryptophan depletion and catecholamine depletion, but not sham depletion, induced a transient exacerbation of depressive symptoms (p <.001); plasma neopterin levels increased during tryptophan depletion and catecholamine depletion (p <.05). Tryptophan depletion and catecholamine depletion induced a transient reduction of plasma sIL-4 levels (p <.05). A significant correlation was found between sIL-4R levels and depression ratings after tryptophan depletion (r = -.61, p <.05). CONCLUSIONS: The monoamine depletion-induced alterations of humoral and cellular immunity suggest a potential role of immunologic parameters in the pathophysiology of seasonal affective disorder; however, the results must be considered preliminary and require further study
— id: 146350, year: 2003, vol: 53, page: 332, stat: Journal Article,

Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression
Neumeister, Alexander; Konstantinidis, Anastasios; Stastny, Juergen; Schwarz, Markus J; Vitouch, Oliver; Willeit, Matthaus; Praschak-Rieder, Nicole; Zach, Johanna; de Zwaan, Martina; Bondy, Brigitta; Ackenheil, Manfred; Kasper, Siegfried
2002 Jul;59(7):613-620, Archives of general psychiatry
BACKGROUND: Evidence suggests that serotonin transporter gene promoter polymorphism (5HTTLPR)-dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. We studied the behavioral responses to tryptophan depletion (TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles. METHODS: Twenty-four healthy women with a negative family history of depression and 21 women with a positive family history of depression were genotyped for the polymorphism of the 5HTTLPR and then entered a double-blind, placebo-controlled, randomized crossover TD study. The effects of these interventions were assessed with measures of depression and plasma tryptophan levels. RESULTS: The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermediate between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects. CONCLUSIONS: The results of the present study suggest that the s-allele of the 5HTTLPR and a positive family history of depression are additive risk factors for the development of depression during TD
— id: 146353, year: 2002, vol: 59, page: 613, stat: Journal Article,

Outcome measurement in somatoform disorders
Santos, Manuel; Schwarz, Melanie; Aladjem, Asher
Outcome measurement in psychiatry: A critical review Washington, DC, US: American Psychiatric Publishing, Inc., 2002,
(from the chapter) This chapter reviews the tools available (as determined by a literature search of MEDLINE from 1966 to January 2000) for outcome measures for the cluster of somatoform disorders identified in DSM-IV-TR. The following instruments are discussed: for the measurement of somatization disorder, the Symptom Checklist-90; for the measurement of conversion disorder, the Placebo Infusion Test, Minnesota Multiphasic Personality Inventory, and Glasgow-Edinburgh Throat Scale; and for the measurement of pain disorder, the Pain Anxiety Symptoms Scale and the Patient Pain Profile Scale. Tools for the measurement of hypochondriasis include the Whiteley Index, the Somatosensory Amplification Scale, and the Structured Diagnostic Interview for Hypochondriasis. Body dysmorphic disorder is measured with the Yale-Brown Obsessive-Compulsive Scale modified for Body Dysmorphic Disorder and the Brown Assessment of Beliefs Scale.
— id: 3007, year: 2002, vol: , page: 221, stat: Chapter,