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.

中文翻译：

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杏仁核的血清素神经支配在自闭症谱系障碍中增加，而在威廉姆斯综合征中减少。


背景威廉姆斯综合征（WS）和自闭症谱系障碍（ASD）是神经发育障碍，表现出重叠的遗传关联、二分的社会行为表型以及关键社会大脑区域（包括前额皮质和杏仁核）神经元分布的二分病理差异。血清素能系统对于神经发育的许多过程至关重要，而且还是与行为变化相关的重要神经调节剂。杏仁核受到血清素能投射的严重支配，表明血清素能系统是神经元活动的重要调节者。 WS 和 ASD 均涉及血清素能系统的破坏以及杏仁核的非典型结构和功能。方法 我们对被诊断患有 ASD 和 WS 的个体死后大脑以及神经典型 (NT) 大脑中杏仁核四个主要分区的血清素轴突密度进行了量化。结果我们发现这两种疾病的血清素能神经支配变化方向相反，ASD 的血清素能轴突增加，而 NT 和 WS 则减少。在多个杏仁核的 WS 和 ASD 数据集之间观察到显着差异 (p < 0.05)。局限性本研究受到人类死后组织可用性的限制。小样本量是大多数人脑死后研究，特别是罕见疾病死后研究不可避免的限制。结论 杏仁核血清素能神经支配的差异性改变可能导致 WS 和 ASD 社会行为表型的差异。 这些发现将为未来的工作提供信息，以确定这些疾病和其他以非典型社会行为为特征的疾病的未来治疗目标。