Serotonergic innervation of the amygdala is increased in autism spectrum disorder and decreased in Williams syndrome

Abstract

Abstract Background Williams syndrome (WS) and autism spectrum disorder (ASD) are neurodevelopmental disorders that demonstrate overlapping genetic associations, dichotomous sociobehavioral phenotypes, and dichotomous pathological differences in neuronal distribution in key social brain areas, including the prefrontal cortex and the amygdala. The serotonergic system is critical to many processes underlying neurodevelopment and is additionally an important neuromodulator associated with behavioral variation. The amygdala is heavily innervated by serotonergic projections, suggesting that the serotonergic system is a significant mediator of neuronal activity. Disruptions to the serotonergic system, and atypical structure and function of the amygdala, are implicated in both WS and ASD. Methods We quantified the serotonergic axon density in the four major subdivisions of the amygdala in the postmortem brains of individuals diagnosed with ASD and WS and neurotypical (NT) brains. Results We found opposing directions of change in serotonergic innervation in the two disorders, with ASD displaying an increase in serotonergic axons compared to NT and WS displaying a decrease. Significant differences (p < 0.05) were observed between WS and ASD data sets across multiple amygdala nuclei. Limitations This study is limited by the availability of human postmortem tissue. Small sample size is an unavoidable limitation of most postmortem human brain research and particularly postmortem research in rare disorders. Conclusions Differential alterations to serotonergic innervation of the amygdala may contribute to differences in sociobehavioral phenotype in WS and ASD. These findings will inform future work identifying targets for future therapeutics in these and other disorders characterized by atypical social behavior.