Kawatake-Kuno Ayako, Leventhal Michael B, Morishita Hirofumi
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Neuropsychopharmacology. 2025 Jul 4. doi: 10.1038/s41386-025-02156-6.
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.
社交缺陷是许多精神疾病的核心特征。重要的是，童年和青少年时期异常的社交经历会深刻影响大脑功能的成熟，并在成年后导致社交障碍。社交隔离，尤其是在青少年中，已被视为对心理健康的严重威胁。因此，从机制层面理解社交隔离的后果变得越来越紧迫。最近的啮齿动物研究表明，发育期间的社交隔离会导致成年大脑结构发生广泛变化，尤其是前额叶皮层回路，并导致社交行为改变。这些发现促使我们提出两种模型，即社交隔离可能通过与社交中断同时发生（社会剥夺模型）或随后发生（发育不匹配模型）而导致缺陷。基于这两种模型，本综述探讨了这些模型如何为社交隔离对精神分裂症从前驱期到精神病期进展的影响提供互补观点，在这种疾病中，遗传和环境风险因素与社交隔离密切相关。通过这些模型来加深我们对隔离引起的社交缺陷的治疗时机和靶点的理解，可能有助于确定针对精神分裂症的有效干预和预防策略的最佳发育时机。
