Effects of tryptophan depletion in panic disorder

Abstract

Tryptophan (TRP) depletion is a useful paradigm for evaluating serotonin (5-HT) function in psychiatric disease. Primate studies have shown that plasma TRP depletion can be induced by the ingestion of an amino acid (AA) mixture lacking TRIP (Young et al ! 989). In this report the AA mixture without TRP reduced cerebrospinal fluid (CSF) TRP by 61% relative to a control AA mixture, which effect was associated with a 34% reduction in 5-hydroxyindole, acetic acid. Oral administration of this AA mixture following a Iow-TRP diet is known to reduce plasma TRP levels in healthy humans by over 80% of baseline levels (Zimmerman et a l i 993). In other clinical studies we have found that TRP depletion by this method produces a transient exacerbation of depressive symptoms in antidepressant-remitted depressed (Delgado et al 1990) and obsessive-compulsive patients (Barr et al 1994); however, to date there have been no studies utilizing TRP depletion in panic disorder (PD) patients. The norepinephrine (NE) and 5-HT systems have been implicated in the pathophysiology of PD (Kahn et al ! 988a, Charney et al 1992). Furthermore, the 5-HT system may provide inhibitory inputs to the principal NE nucleus, the locus coeruleus (AstonJones et ai ! 99 I). If TRP depletion sufficiently reduced presynaptic 5-HT inhibition of NE function in PD patients, this could lead to a transient increase in NE function with accompanying increases in anxiety, blood pressure, and the NE metabolite 3-methoxy-4hydroxyphenylglycol (MHPG).