Our work thus far has investigated the effects of altering serotonergic systems in humans using acute tryptophan depletion on behavioral performance during emotional processing tasks. Moreover, we have begun to determine how acute tryptophan depletions effects on emotional processing vary as a function of serotonin transporter genotype. This project is associated with three core findings: (i) Genotype and acute tryptophan depletion modulate dissociable components of emotional expression processing and that the effects of altering serotonin transmission via tryptophan depletion are genotype-dependent. Tryptophan depletion in and of itself did not disrupt fear expression recognition. However, it did impair fear recognition in individuals who carried the short allele of the serotonin transporter gene. This indicates that genotype or changes in serotonergic transmission alone may not necessarily be sufficient to affect processing of social cues, but genotype may influence this domain of emotional processing when faced with a pharmacological challenge or when serotonin systems are altered. (ii) A form of emotional processing that is important in the context of mood and anxiety disorders is reinforcement processing. Processing reward and punishment directly guides behaviors and decision making, and atypical reinforcement processing occurs in a variety of psychiatric conditions. We have found that altering serotonin systems via acute tryptophan depletion altered reinforcement processing, and again that this effect was, in some cases, genotype dependent. (iii) The salience of the victim's distress in moral decision making is influenced by genotype. Individuals carrying the short allele of the serotonin transporter show increased sensitivity to the victim's distress in a moral judgment task. In studies either recently completed or currently on-going, we have assessed: (i) The impact at the neural level of tryptophan depletion on the neural systems engaged in reinforcement processing. (ii) The impact to the neural level of tryptophan depletion on the neural systems engaged in emotional attention.

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U.S. National Institute of Mental Health
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