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. Additionally, we have begun to determine how acute tryptophan depletions effects on emotional processing vary as a function of serotonin transporter genotype. We have found that both genotype and acute tryptophan depletion modulated dissociable components of emotional processing and that the effects of altering serotonin transmission via tryptophan depletion were often genotype-dependent. For example, although tryptophan depletion in and of itself did not disrupt fear expression recognition, 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. 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. In the work that has been on-going over the past 12 months, we have used functional magnetic resonance imaging to determine the selective effects of tryptophan depletion on neural regions particularly those engaged in expression processing, emotional attention and reversal learning.
| Mitchell, Derek G V; Luo, Qian; Avny, Shelley B et al. (2009) Adapting to dynamic stimulus-response values: differential contributions of inferior frontal, dorsomedial, and dorsolateral regions of prefrontal cortex to decision making. J Neurosci 29:10827-34 |
| Blair, K S; Finger, E; Marsh, A A et al. (2008) The role of 5-HTTLPR in choosing the lesser of two evils, the better of two goods: examining the impact of 5-HTTLPR genotype and tryptophan depletion in object choice. Psychopharmacology (Berl) 196:29-38 |
