Serotonin differentially modulates the temporal dynamics of the limbic response to facial emotions in male adults with and without autism spectrum disorder (ASD): a randomised placebo-controlled single-dose crossover trial

Abstract

Emotion processing—including signals from facial expressions—is often altered in individuals with autism spectrum disorder (ASD). The biological basis of this is poorly understood but may include neurochemically mediated differences in the responsivity of key ‘limbic’ regions (including amygdala, ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAc)). Emerging evidence also suggests that ASD may be a disorder of brain temporal dynamics. Moreover, serotonin (5-HT) has been shown to be a key regulator of both facial-emotion processing and brain dynamics, and 5-HT abnormalities have been consistently implicated in ASD. To date, however, no one has examined how 5-HT influences the dynamics of facial-emotion processing in ASD. Therefore, we compared the influence of 5-HT on the responsivity of brain dynamics during facial-emotion processing in individuals with and without ASD. Participants completed a facial-emotion processing fMRI task at least 8 days apart using a randomised double-blind crossover design. At each visit they received either a single 20-mg oral dose of the selective serotonin reuptake inhibitor (SSRI) citalopram or placebo. We found that citalopram (which increases levels of 5-HT) caused sustained activation in key limbic regions during processing of negative facial emotions in adults with ASD—but not in neurotypical adults. The neurotypical adults’ limbic response reverted more rapidly to baseline following a 5-HT-challenge. Our results suggest that serotonergic homoeostatic control of the temporal dynamics in limbic regions is altered in adults with ASD, and provide a fresh perspective on the biology of ASD.