Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem brain studies, and analyses from cellular models that recapitulate neurodevelopment. Emerging insights into schizophrenia genetic risk continue to converge on brain development, particularly stages of early brain development, that may be perturbed to deviate from a typical, normative course, resulting in schizophrenia clinical symptomatology. As the authors explicate, schizophrenia genetic risk is likely dynamic and context dependent, with effects of genetic risk varying spatiotemporally, across the neurodevelopmental continuum. Optimizing therapeutic strategies for the heterogeneous collective of individuals with schizophrenia may likely be guided by leveraging markers of genetic risk and derivative functional insights, well before the emergence of psychosis. Ultimately, rather than a focus on therapeutic intervention during adolescence or adulthood, principles of prediction and prophylaxis in the pre- and perinatal and neonatal stages may best comport with the biology of schizophrenia to address the early-stage perturbations that alter the normative neurodevelopmental trajectory.

精神分裂症通常被称为一种神经发育障碍，但大脑发育在这种通常在成年早期诊断出的疾病中的作用却是一个谜。作者利用最新精神分裂症临床遗传关联研究的基因组见解、人类死后大脑研究的转录组和表观基因组分析以及概括神经发育的细胞模型的分析，重新审视了精神分裂症的神经发育模型。对精神分裂症遗传风险的新见解继续集中在大脑发育，特别是早期大脑发育阶段，这些阶段可能会受到干扰而偏离典型的规范过程，从而导致精神分裂症的临床症状。正如作者所解释的那样，精神分裂症的遗传风险可能是动态的且依赖于环境，遗传风险的影响在整个神经发育连续体中随时空变化。早在精神病出现之前，就可以通过利用遗传风险标记和衍生功能见解来指导优化针对精神分裂症患者的异质群体的治疗策略。最终，与关注青春期或成年期的治疗干预不同，产前、围产期和新生儿阶段的预测和预防原则可能最符合精神分裂症的生物学特性，以解决改变正常神经发育轨迹的早期扰动。