title: Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.
abstract: 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.
authors.affiliation: Innovative Research Division, Mitsubishi Tanabe Pharma, Yokohama, Japan Nakagawa.Yutaka@mf.mt-pharma.co.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Innovative Research Division, Mitsubishi Tanabe Pharma, Yokohama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000150:complications; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D012919:Social Behavior