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J. Douglas Bremner, MD; Robert B. Innis, MD, PhD; Ronald M. Salomon, MD; Lawrence H. Staib, PhD; Chin K. Ng, PhD; Helen L. Miller, MD; Richard A. Bronen, MD; John H. Krystal, MD; James Duncan, PhD; Dayton Rich; Lawrence H. Price, MD; Robert Malison, MD; Holley Dey, MD; Robert Soufer, MD; Dennis S. Charney, MD

Arch Gen Psychiatry. 1997;54(4):364-374.

Abstract
Background
Short-term depletion of plasma tryptophan has been shown to result in depressive relapse in patients with remission of major depression. Positron emission tomography and single photon emission computed tomography studies implicated the dorsolateral prefrontal cortex, orbitofrontal cortex, thalamus, and caudate nucleus in the pathogenesis of depression. The purpose of this study was to measure cerebral metabolic correlates of tryptophan depletion—induced depressive relapse.

Methods
Patients diagnosed as having major depression (N=21) who clinically improved with serotonin reuptake inhibitors underwent 2 test days involving tryptophan depletion or placebo, followed 6 hours later by positron emission tomography scanning with fludeoxy-glucose F18. Brain metabolism was compared in patients with (n=7) and without (n=14) a tryptophan depletion—induced depressive relapse.

Results
Tryptophan depletion resulted in a decrease in brain metabolism in the middle frontal gyrus (dorsolateral prefrontal cortex), thalamus, and orbitofrontal cortex in patients with a depletion-induced depressive relapse (but not in patients without depletion-induced relapse). Decreased brain metabolism in these regions correlated with increased depressive symptoms. Baseline metabolism was increased in prefrontal and limbic regions in relapse-prone patients.

Conclusion
Specific brain regions, including the middle frontal gyrus, thalamus, and orbitofrontal cortex, may mediate the symptoms of patients with major depression.

Author Affiliations
From the Departments of Psychiatry (Drs Bremner, Innis, Salomon, Miller, Krystal, Price, Malison, and Charney) and Diagnostic Radiology (Nuclear Medicine (Drs Bremner, Staib, Ng, Duncan, Dey, and Soufer] and Neuroradiology [Dr Bronen]), Yale University School of Medicine, New Haven, Conn; and the National Center for Posttraumatic Stress Disorder (Drs Bremner, Innis, Krystal, and Charney), West Haven Veterans Affairs Medical Center (Drs Bremner, Innis, Salomon, Ng, Miller, Krystal, Dey, Soufer, and Charney and Mr Rich), and the Yale/Veterans Affairs Positron Emission Tomography Center (Drs Ng, Dey, and Soufer and Mr Rich), West Haven, Conn.

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