Serotonin and the Neural Processing of Facial Emotions in Adults With Autism An fMRI Study Using Acute Tryptophan Depletion

Context: People with autism spectrum disorders (ASDs) have lifelong deficits in social behavior and differences in behavioral as well as neural responses to facial expressions of emotion. The biological basis to this is incompletely understood, but it may include differences in the role of neurotransmitters such as serotonin, which modulate facial emotion processing in health. While some individuals with ASD have significant differences in the serotonin system, to our knowledge, no one has investigated its role during facial emotion processing in adults with ASD and control subjects using acute tryptophan depletion (ATD) and functional magnetic resonance imaging. Objective: To compare the effects of ATD on brain responses to primary facial expressions of emotion in men with ASD and healthy control subjects. Design: Double-blind, placebo-controlled, crossover trial of ATD and functional magnetic resonance imaging to measure brain activity during incidental processing of disgust, fearful, happy, and sad facial expressions. Setting: Institute of Psychiatry, King's College London, and South London and Maudsley National Health Service Foundation Trust, England. Participants: Fourteen men of normal intelligence with autism and 14 control subjects who did not significantly differ in sex, age, or overall intelligence. Main Outcome Measures: Blood oxygenation level-dependent response to facial expressions of emotion. Results: Brain activation was differentially modulated by ATD depending on diagnostic group and emotion type within regions of the social brain network. For example, processing of disgust faces was associated with interactions in medial frontal and lingual gyri, whereas processing of happy faces was associated with interactions in middle frontal gyrus and putamen. Conclusions: Modulation of the processing of facial expressions of emotion by serotonin significantly differs in people with ASD compared with control subjects. The differences vary with emotion type and occur in social brain regions that have been shown to be associated with group differences in serotonin synthesis/receptor or transporter density. Arch Gen Psychiatry. 2012; 69(10): 1003-1013. Published online June 4, 2012. doi: 10.1001/archgenpsychiatry.2012.513