Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine , Detroit, MI , USA.
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine , Detroit, MI , USA.
Front Psychiatry. 2014 Jun 23;5:71. doi: 10.3389/fpsyt.2014.00071. eCollection 2014.
The recent sociodevelopmental cognitive model of schizophrenia/psychosis is a highly influential and compelling compendium of research findings. Here, we present logical extensions to this model incorporating ideas drawn from epigenetic mediation of psychiatric disease, and the plausible effects of epigenetics on the emergence of brain network function and dysfunction in adolescence. We discuss how gene-environment interactions, effected by epigenetic mechanisms, might in particular mediate the stress response (itself heavily implicated in the emergence of schizophrenia). Next, we discuss the plausible relevance of this framework for adolescent genetic risk populations, a risk group characterized by vexing and difficult-to-explain heterogeneity. We then discuss how exploring relationships between epigenetics and brain network dysfunction (a strongly validated finding in risk populations) can enhance understanding of the relationship between stress, epigenetics, and functional neurobiology, and the relevance of this relationship for the eventual emergence of schizophrenia/psychosis. We suggest that these considerations can expand the impact of models such as the sociodevelopmental cognitive model, increasing their explanatory reach. Ultimately, integration of these lines of research may enhance efforts of early identification, intervention, and treatment in adolescents at-risk for schizophrenia.
精神分裂症/精神病的近期社会发展认知模型是一个极具影响力和说服力的研究成果汇编。在这里，我们将从表观遗传学介导的精神疾病以及表观遗传学对青少年大脑网络功能和功能障碍出现的可能影响中汲取灵感，对该模型进行逻辑扩展。我们讨论了基因-环境相互作用如何通过表观遗传机制介导应激反应（其本身与精神分裂症的出现密切相关）。接下来，我们讨论了该框架对于青少年遗传风险人群的可能相关性，这是一个风险群体，其特点是令人困扰且难以解释的异质性。然后，我们讨论了探索表观遗传学与大脑网络功能障碍之间的关系（在风险人群中得到了强烈验证的发现）如何增强对压力、表观遗传学和功能神经生物学之间关系的理解，以及这种关系与精神分裂症/精神病最终出现的相关性。我们认为，这些考虑因素可以扩大社会发展认知模型等模型的影响范围，增加其解释力。最终，这些研究方向的整合可能会增强对精神分裂症高危青少年进行早期识别、干预和治疗的努力。
