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Effects of rapid tryptophan depletion on brain 5-HT₂ receptors: a PET study

Division of Mood Disorders, The University of British Columbia

PETER F. LIDDLE, MBBS

Division of Schizophrenia, The University of British Columbia

I-SHIN SHIAH, PhD

Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Centre, Taipei, Taiwan

RAYMOND W. LAM, MD

Division of Mood Disorders, The University of British Columbia

MICHAEL J. ADAM, PhD

TRIUMF Positron Emission Tomography Programme, The University of British Columbia

ATHANASIOS P. ZIS, MD

Division of Mood Disorders, The University of British Columbia

THOMAS J. RUTH, PhD

TRIUMF Positron Emission Tomography Programme, The University of British Columbia, Vancouver, BC, Canada

Correspondence: Lakshmi N. Yatham, Associate Professor of Psychiatry, Director of Mood Disorders Clinical Research Unit, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 2A1. Tel: 1 604 822 0562; Fax: 1 604 822 7922; e-mail: yatham{at}unixg.ubc.ca

Declaration of interest None.

Background The mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown.

Aims To determine the effects of RTD on brain 5-HT₂ receptors using positron emission tomography (PET) and ¹⁸F-labelled setoperone.

Method Ten healthy women under went two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days.

Results The RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT₂ receptor binding in various cortical regions following the RTD session.

Conclusions When taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT₂ receptors, these findings suggest that a decrease in 5-HT₂ binding following RTD might be an adaptive response that provides protection against depressive symptoms.

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