Acute Tryptophan Depletion in Healthy Volunteers Enhances Punishment Prediction but Does not Affect Reward Prediction

Abstract

Central serotonin (5-HT) has been implicated in emotional and behavioral control processes for many decades, but its precise contribution is not well understood. We used the acute tryptophan depletion procedure in young healthy volunteers to test the hypothesis that central 5-HT is critical for predicting punishment. An observational reversal-learning task was employed that provided separate measures of punishment and reward prediction. Under baseline, subjects made more prediction errors for punishmentassociated stimuli than for reward-associated stimuli. This bias was abolished after central 5-HT depletion, which enhanced the ability to predict punishment while not affecting reward prediction. The selective potentiation of punishment prediction concurs with recent theorizing, suggesting that central 5-HT carries a prediction error for future punishment, but not for future reward (Daw et al, 2002). Furthermore, the finding highlights the importance of central 5-HT in resilience to adversity and may have implications for a variety of neuropsychiatric disorders including depression and anxiety.

Serotonin and Dopamine Play Complementary Roles in Gambling to Recover Losses

“…From this perspective, loss chasing can be viewed as an aversively motivated escape behavior, but one controlled, at least in part, by the marginal utility of continued play relative to its cessation. Our finding that tryptophan depletion reduced our behavioral model of loss chasing suggests that, in this instance at least, diminished central serotonin activity reduced the marginal utility of continued play by increasing the salience of future bad outcomes across the range of values encountered during the game (Cools et al, 2008;Deakin and Graeff, 1991).…”

“…By contrast, serotonin activity also plays a significant role in learning from, and coping with, aversive events (Bari et al, 2010;Daw et al, 2002;Deakin and Graeff, 1991;Evers et al, 2005). Given that tryptophan depletion can also improve the prediction of punishing outcomes (Cools et al, 2008), and enhance neural responses to punishing outcomes within the anterior cingulate cortex (Evers et al, 2005), we also anticipated that tryptophan depletion might increase the salience of bad outcomes and diminish loss-chasing behavior. In fact, while producing no marked changes in healthy adults' state affect, tryptophan depletion significantly reduced the proportion of decisions participants made to chase losses, and reduced the number of consecutive decisions to chase, during a run of losing gambles.…”

“…Dayan and Huys (2008) has proposed that failures of behavioral control following reductions in serotonin activity (experimental or clinical) can produce pervasive increases in the size of negative prediction errors that, in turn, engender negative affective states in vulnerable individuals (Dayan and Huys, 2008). Experimentally, tryptophan depletion can improve the accuracy of predictions of negative or punishing outcomes in healthy adults (Cools et al, 2008). Moreover, Evers et al (2005) showed that tryptophan depletion enhances neural activity in response to errors during reversal learning within the anterior cingulate region, an area that is activated while making decisions to stop chasing losses (Campbell-Meiklejohn et al, 2008).…”

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

“…Moreover, if serotonin activity can influence the activity of positive vs negative cognitive biases, it should not surprise that tryptophan depletion and other manipulations that enhance such biases find greater expression in the processing of negative choice outcomes (Cools et al, 2008b;Dayan and Huys, 2008), as aversive events more frequently warrant reappraisal. Indeed, this proposal is reminiscent of an older theory suggested that activity of the dorsal raphe nucleus might mediate coping responses to such events (Deakin, 1998;Deakin and Graeff, 1991), and that variation in the functioning of the ascending serotonin system confers vulnerability to psychological disorders involving depression and anxiety (Deakin and Graeff, 1991).…”

Serotonin Modulates Sensitivity to Reward and Negative Feedback in a Probabilistic Reversal Learning Task in Rats

“…Accordingly, the majority of studies on cognitive and affective processing in depressed patients highlight strong biases toward negative stimuli and away from positive ones, which interfere with normal cognitive functioning (Elliott et al, , 1997Gotlib et al, 2004;Murphy et al, 2003;Roiser et al, 2009;Siegle et al, 2001), whereas long-term treatment with selective serotonin reuptake inhibitors (SSRIs) counteracts these biases. Moreover, lowering brain content of 5-HT by acute tryptophan depletion (ATD) in healthy subjects causes similar biases in neuropsychological tasks assessing affective decisionmaking and punishment prediction (Cools et al, 2008b;Murphy et al, 2002;Rogers et al, 2003;Roiser et al, 2006). In addition, in rats and other animals, 5-HT modulates the processing of aversive stimuli (Burghardt et al, 2004;Dayan and Huys, 2009;Inoue et al, 2004;Stutzmann and LeDoux, 1999;Wilkinson et al, 1995).…”