Effects of Acute Tryptophan Depletion on Mood and Cognitive Functioning in Older Recovered Depressed Subjects

Abstract

Previous studies show that acute tryptophan depletion (ATD), by administration of an amino acid drink lacking tryptophan, can produce clinically significant depressive symptoms in subjects who have recovered from major depression. This is more likely in female patients who have had suicidal ideation, recurrent depression, and treatment with specific serotonin reuptake inhibitors. These risk factors are frequent in older recovered depressed people. The authors investigated the effects of ATD on mood and cognitive functioning in this group. Sixteen recovered depressed (RD) subjects and 17 healthy-comparison subjects, over 60 years old, participated in a double-blind, placebo-controlled, crossover study involving administration of a tryptophan-depleting and a placebo drink. Mood ratings scales were administered at baseline and at 4 and 7 hours post-drink on each test day. A battery of neuropsychological tests, including the modified Mini-Mental State Examination (MMSE) was administered between 4 and 6 hours post-drink. Depletion of plasma free tryptophan was 71% at 4 and 7 hours after the active drink. There was no evidence of mood change at any time in either group. On the MMSE, however, the ATD/RD group showed a significant decrease compared with placebo. There was no evidence of mood disturbance during ATD in any subject. This may imply less sensitivity to acute disturbance of the 5HT system than in younger recovered patients.