Review: Dopamine, Serotonin, and the Translational Neuroscience of Aggression in Autism Spectrum Disorder.

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a 1% to 2% prevalence in children. In addition to social communication deficits and restricted or repetitive behavior, ASD is often characterized by a heightened propensity for aggression. In fact, aggressive behavior is the primary reason for hospitalization in children with ASD, and current treatment options, despite some efficacy, are often associated with prominent side effects. Despite such high clinical toll, the neurobiology of aggression in ASD remains poorly understood. Method: The neural circuits linked to both ASD and aggression were reviewed, with the goal of identifying overlapping components to help guide future treatment development. In discussing the clinical phenotype of aggression in ASD, some of the triggers and risk factors were noted to differ from those that cause aggression in neurotypical children. Preclinical and clinical studies on the neurobiology of aggression and ASD were synthesized to combine evidence from genetics, neuroimaging, pharmacology, and circuit manipulations. Dopamine and serotonin, 2 neuromodulators that contribute to development and behavioral control, were specifically studied. Results: The literature indicates that the intricate interplay of the dopamine and serotonin systems has a pivotal role in shaping behavior, including the expression of aggression. Conclusion: Understanding the balance between dopamine as an accelerator and serotonin as a brake may provide insights into the mechanisms of aggression in children with ASD. Although much work remains to be done, new perspectives promise to bridge the gap between human and animal studies and pinpoint the neurobiology of aggression in ASD. Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group.