RAPID DEPLETION OF PLASMA TRYPTOPHAN - A REVIEW OF STUDIES AND EXPERIMENTAL METHODOLOGY

Evidence that the neurotransmitter serotonin (5-hydroxytryptamine, 5-H T) plays a role in the pathophysiology of mood disorders has been accu mulating over the past three decades. Recent studies on this neurotran smitter have extended across the spectrum of psychiatric disorder, sug gesting a role for 5-HT in psychosis, aggression, eating disorders and addiction. However, much of the evidence has come from post-mortem ex amination of the brain or measures of peripheral rather than central 5 -HT function. The technique of tryptophan depletion allows investigati on of brain 5-HT function in living subjects by examining the behaviou ral responses to this pharmacological challenge. This review considers the current status of tryptophan depletion as an experimental techniq ue and discusses the implications of findings both in affective disord ers and in a range of other psychiatric syndromes. MEDLINE and PSYCHLI T searches were completed for the years 1966 to November 1996 using th e key words 'serotonin', '5-hydroxytryptamine', 'tryptophan' and 'depl etion'. In addition relevant journals were hand-searched for the perio d from 1980 to December 1996. Forty-four double-blind studies in human s and three clinical case reports were identified; these cover a range of psychiatric disorders including mood disorders and psychoses, anxi ety and eating disorders and specific behaviours such as appetite, agg ression and craving. The studies reviewed utilized a variety of differ ing methodologies reducing the extent to which results can be generali zed. A series of studies in depressed patients (before and after treat ment with antidepressants) and their first-degree relatives have shown the importance of an intact 5-HT system in the action of antidepressa nts and offer new insights into the biology of affective disorder. The mood change induced by tryptophan depletion may predict those patient s likely to respond to 5-HT-specific drugs. Rapid tryptophan depletion has also been reported to exacerbate both panic and aggression in vul nerable individuals. Effects in other disorders are conflicting and fu rther research is needed to clarify these findings.