Neurodevelopmental and neuropsychiatric disorders

Abstract

The etiology of neuropsychiatric disorders such as autism spectrum disorders (ASDs) and schizophrenia remains unclear. However, many aspects of their neuropathology were recently reported to be closely associated with microglial dysfunction. Microglia, which are the major players of innate immunity in the central nervous system, respond rapidly to pathological changes, even minor ones, and contribute directly to neuroinflammation by producing various cytokines and free radicals. Recent studies revealed that microglia become activated over the course of ASDs and schizophrenia, using brain neuroimaging and postmortem analyzes. Recent studies have also shown inhibitory effects of some antipsychotics on the release of inflammatory cytokines and free radicals from activated microglia, causing synaptic and white matter abnormalities as seen in ASDs and schizophrenia postmortem brains. In addition, recent evidence strongly suggests a neurodevelopmental role for microglia in regulating the formation/function of neuronal circuits by their phagocytic activity and structural interactions with synapses. In Rett syndrome (RTT) particularly, microglia become dysfunctional and neurotoxic, thus contributing to abnormal brain development. Populating the brain of RTT mice with wild-type microglia was also found to arrest the disease, indicating an essential role of microglia in regulating the neurodevelopmental trajectory. In summary, emerging evidence indicates that microglia are closely related to the progression and outcome of ASDs and schizophrenia. Understanding microglial pathology may shed new light on the most promising therapeutic strategies for ASDs and schizophrenia, among other neuropsychiatric disorders.