 |
|
Neural and Behavioral Responses to Tryptophan Depletion in Unmedicated Patients With Remitted Major Depressive Disorder and Controls
Alexander Neumeister, MD;
Allison C. Nugent, PhD;
Tracy Waldeck, PhD;
Marilla Geraci, RN;
Markus Schwarz, MD;
Omer Bonne, MD;
Earle E. Bain, MD;
David A. Luckenbaugh, MA;
Peter Herscovitch, MD;
Dennis S. Charney, MD;
Wayne C. Drevets, MD
Arch Gen Psychiatry. 2004;61:765-773.
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.
From the Sections on Experimental Therapeutics and Pathophysiology (Drs Neumeister, Waldeck, Bonne, and Charney; Ms Geraci; and Mr Luckenbaugh) and Neuroimaging in Mood and Anxiety Disorders (Drs Nugent, Bain, and Drevets), Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Md; the Department of Neurochemistry, University Hospital of Psychiatry, Munich, Germany (Dr Schwarz); and the PET Department, Clinical Center, National Institutes of Health, Bethesda (Dr Herscovitch). Dr Neumeister is now with the Department of Psychiatry, Yale University, New Haven, Conn.
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Neural Response to Catecholamine Depletion in Unmedicated Subjects With Major Depressive Disorder in Remission and Healthy Subjects
Hasler et al.
Arch Gen Psychiatry 2008;65:521-531.
ABSTRACT
| FULL TEXT
The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings
Epperson et al.
J Psychopharmacol 2007;21:414-420.
ABSTRACT
Lack of Ventral Striatal Response to Positive Stimuli in Depressed Versus Normal Subjects
Epstein et al.
Am. J. Psychiatry 2006;163:1784-1790.
ABSTRACT
| FULL TEXT
Differential Effects of 5-HTTLPR Genotypes on the Behavioral and Neural Responses to Tryptophan Depletion in Patients With Major Depression and Controls.
Neumeister et al.
Arch Gen Psychiatry 2006;63:978-986.
ABSTRACT
| FULL TEXT
Major Depressive Episodes and Random Mood.
van der Werf et al.
Arch Gen Psychiatry 2006;63:509-518.
ABSTRACT
| FULL TEXT
Functional Neuroanatomical Substrates of Altered Reward Processing in Major Depressive Disorder Revealed by a Dopaminergic Probe
Tremblay et al.
Arch Gen Psychiatry 2005;62:1228-1236.
ABSTRACT
| FULL TEXT
Effects of Acute Tryptophan Depletion on Mood and Cognitive Functioning in Older Recovered Depressed Subjects
Porter et al.
AJGP 2005;13:607-615.
ABSTRACT
| FULL TEXT
Developmental disruption of serotonin transporter function impairs cerebral responses to whisker stimulation in mice
Esaki et al.
Proc. Natl. Acad. Sci. USA 2005;102:5582-5587.
ABSTRACT
| FULL TEXT
|
