The tryptophan depletion challenge test in medical research: unresolved issues and broader implications for the use of physiological challenges to investigate and categorize disease.

摘要

In this issue of Biological Psychiatry, Feder et al. (1) add to the literature showing that acute depletion of tryptophan (ATD) is more likely to induce depression-like changes in never-depressed subjects with a family history of a mood disorder (high risk [HR]), compared with similar subjects with no family history of mood disorder (low risk [LR]). Specifically, HR subjects tended to make more inappropriate responses to "sad" distracters during happy target blocks than to "happy" distracters during sad target blocks in the affective goo-go task. They conclude that serotonin (5-HT) "might be more directly linked to affective processing than mood per se" and hypothesize that "abnormal 5-HT function in HR individuals might induce bias toward sad stimuli, resulting in reduced engagement in potentially rewarding activities or interactions with others, and a complex iterative cycle ultimately leading to first onset" of major depression.