Impact of early social isolation on social circuits and behavior: relevance to schizophrenia

Social deficits are a core feature of many psychiatric disorders. Importantly, aberrant social experiences during childhood and adolescence profoundly influence maturation of the brain function and induce social impairments in adulthood. Social isolation, especially among youth, has been highlighted as a serious risk to mental health. As a result, understanding the consequences of social isolation on a mechanistic level has become increasingly urgent. Recent rodent studies have revealed that social isolation during development induces widespread changes in adult brain structures, particularly in the prefrontal cortical circuits, and causes altered social behavior. These findings led us to develop two models proposing that social isolation may cause deficits through either concurrent (social deprivation model) or subsequent (developmental mismatch model) to social disruption. Building on these two models, this review examines how these models provide complementary perspectives on the influence of social isolation on the progression of schizophrenia, from the prodromal to the psychotic phase, a condition in which genetic and environmental risk factors are closely linked to social isolation. Advancing our understanding of treatment timing and targets for isolation-induced social deficits through the lenses of these models may help identify the optimal developmental timing for effective interventions and prevention strategies for schizophrenia.