Department of Anthropology, University of California, San Diego, USA.
Department of Biological Sciences, University of California, San Diego, USA.
Mol Autism. 2020 Feb 5;11(1):12. doi: 10.1186/s13229-019-0302-4.
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.
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.
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.
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.
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.
威廉姆斯综合征（WS）和自闭症谱系障碍（ASD）是神经发育障碍，它们具有重叠的遗传关联、二分社会行为表型以及关键社会脑区（包括前额叶皮层和杏仁核）中神经元分布的二分病理差异。血清素能系统对神经发育的许多过程至关重要，此外，它还是与行为变化相关的重要神经调节剂。杏仁核被血清素能投射大量支配，表明血清素能系统是神经元活动的重要介质。血清素能系统的破坏以及杏仁核的非典型结构和功能与 WS 和 ASD 都有关。
我们在被诊断为 ASD 和 WS 以及神经典型（NT）个体的死后大脑中量化了四个主要杏仁核亚区的血清素能轴突密度。
我们发现两种疾病的血清素能传入存在相反的变化方向，与 NT 相比，ASD 显示血清素能轴突增加，而 WS 则显示减少。在多个杏仁核核中，WS 和 ASD 数据集之间观察到显著差异（p<0.05）。
本研究受到人类死后组织的可用性限制。小样本量是大多数死后人类大脑研究，特别是罕见疾病的死后研究不可避免的限制。
杏仁核血清素能传入的差异可能导致 WS 和 ASD 中社会行为表型的差异。这些发现将为未来在这些和其他以异常社会行为为特征的疾病中确定治疗靶点的工作提供信息。
