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：

---

在自闭症谱系障碍中，杏仁核的血清素能神经支配增加，而在威廉姆斯综合征中则减少。

背景技术Williams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，二分形的社会行为表型以及关键社交脑区域（包括前额叶皮层和杏仁核）中神经元分布的二分型病理差异。血清素能系统对于神经发育的许多过程至关重要，并且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介体。在WS和ASD中都牵涉到血清素能系统的破坏以及杏仁核的非典型结构和功能。方法我们对诊断为ASD和WS以及神经典型（NT）脑的个体的死后大脑杏仁核的四个主要细分区域中的血清素能轴突密度进行了定量。结果我们发现在这两种疾病中，血清素能神经支配的变化方向相反，与NT和WS相比，ASD表现出了血清素能神经轴突的增加。在多个杏仁核之间的WS和ASD数据集之间观察到显着差异（p <0.05）。局限性这项研究受到人类尸体组织可用性的限制。小样本量是大多数事后人类大脑研究，尤其是罕见疾病的事后研究不可避免的局限性。结论杏仁核的血清素能神经支配的差异性改变可能导致WS和ASD的社会行为表型差异。这些发现将为今后确定以非典型社会行为为特征的这些疾病和其他疾病的未来治疗目标提供参考。