Authors:

PASSAMONTI, L., Crockett, M.J., Apergis-Schoute, A.M., Clark, L., ROWE, J.B., CALDER, A.J., and Robbins, T.W.

Reference:

Year of publication:

2012

CBU number:

7303

Abstract:

Background: Reduced levels of serotonin (5-HT) within prefrontal cortex (PFC)-amygdala circuits have long been implicated in impulsive aggression. However, whether lowering 5-HT alters the dynamic interplay between the PFC and the amygdala has not yet been directly tested in humans. It is known that manipulating 5-HT via acute tryptophan depletion (ATD) causes variable effects on brain responses to a variety of emotional stimuli, but it remains unclear whether ATD affects functional connectivity in neural networks involved in processing social signals of aggression (e.g. angry faces). Methods: Thirty healthy individuals were enrolled in a randomized, double-blind, placebo-controlled, ATD study. On each treatment, brain responses to angry, sad and neutral faces were measured with functional magnetic resonance imaging. Two methods (Psycho-Physiological-Interaction in a General Linear Model [PPI-GLM] and Dynamic Causal Modeling [DCM]) were employed to assess the impact of ATD on the functional connectivity between PFC and amygdala. Results: Data from nineteen subjects were available for the final analyses. Whole-brain PPI-GLM showed that ATD significantly modulated the connectivity between the amygdala and two PFC regions (ventral anterior cingulate cortex and ventrolateral PFC) when processing angry vs. neutral and angry vs. sad but not sad vs. neutral faces. DCM corroborated and extended these findings by showing that 5-HT depletion reduced the influence of processing angry vs. neutral faces on circuits within PFC and on PFC-amygdala pathways. Conclusions: We provide strong support for neurobiological accounts positing that 5-HT significantly influences PFC-amygdala circuits implicated in aggression and other affective behaviors.

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