Acute tryptophan depletion evokes negative mood in healthy females who have previously experienced concurrent negative mood and tryptophan depletion

The majority of individuals who suffer an episode of depression go on to experience recurrences. We have proposed, based upon the observation that reducing serotonin via acute tryptophan depletion (ATD) is more likely to induce negative mood in recovered depressed individuals than never depressed individuals, that this may be because associations form between negative mood and reduced serotonin during an episode of depression (Robinson and Sahakian, Psychol Med 38:315-318, 2008b). Such associations would mean that subsequent reductions in serotonin are more likely to provoke depressed mood and hence trigger an episode of depression. In this study, we tested this hypothesis by manipulating the mood state of healthy females undergoing ATD (or balanced placebo) on two separate testing sessions. On the first session, subjects received either negative or neutral mood induction, while on the second session all subjects received neutral mood induction. Our findings demonstrate significant ATD-induced negative mood exclusively on the second visit of subjects who received both ATD and negative mood induction procedure on their first visit. These findings may be explained by the formation of an association between the negative mood and reduced serotonin states during the first visit. As such, these findings provide preliminary support for the associative hypothesis of recurrence in depression. Such associations might therefore explain the discrepancy between the effects of ATD in recovered- and never-depressed individuals and may, in turn, explain why an episode of depression increases the risk of subsequent episodes.