Nakagawa Yutaka, Chiba Kenji
Innovative Research Division, Mitsubishi Tanabe Pharma, Yokohama, Japan
Innovative Research Division, Mitsubishi Tanabe Pharma, Yokohama, Japan.
J Pharmacol Exp Ther. 2016 Sep;358(3):504-15. doi: 10.1124/jpet.116.234476. Epub 2016 Jul 6.
Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset.
社会认知作为一种独特的高阶功能，其发展取决于人类从童年到成年期的大脑成熟过程。自闭症谱系障碍（ASD）和精神分裂症具有相似的社会认知缺陷，尽管每种障碍的发病年龄有所不同。这些障碍的发病机制复杂，包含多个特征，包括遗传风险因素、环境风险因素以及大脑中的异常部位。尽管已经提出了几种假说，但它们似乎不足以解释与这些障碍症状相关的大脑改变是如何在不同发育阶段发生的。ASD的发展似乎与幼儿期小脑功能障碍及随后的丘脑过度激活有关。相比之下，精神分裂症似乎是由青少年晚期的丘脑过度激活引发的，而海马体异常可能在儿童期就已开始。一个可能的罪魁祸首是金属稳态紊乱，它可导致血脑脊髓液屏障功能障碍。丘脑过度激活被认为是由小胶质细胞介导的神经炎症和脑内环境异常所诱发。因此，丘脑过度激活很可能引发与社会认知相关的较低脑区背外侧前额叶皮质的调节失调。在本综述中，我们总结了ASD和精神分裂症中的大脑异常情况，并基于它们不同的发病年龄，提出了这些障碍中社会认知缺陷潜在的一种机制。
