Epigenetics, stress, and their potential impact on brain network function: a focus on the schizophrenia diatheses.

Epigenetics, stress, and their potential impact on brain network function: a focus on the schizophrenia diatheses.
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DOI:
10.3389/fpsyt.2014.00071
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发表时间:
2014
影响因子:
4.7
通讯作者:
Uddin M
Uddin M
中科院分区:
医学3区
文献类型:
--
作者:
Diwadkar VA;Bustamante A;Rai H;Uddin M

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最近的精神分裂症/精神病的社会发展认知模型是一个非常有影响力和令人信服的研究结果纲要。在这里,我们提出了这个模型的逻辑扩展,结合从精神疾病的表观遗传学调解的想法,以及表观遗传学对青春期大脑网络功能和功能障碍的出现的合理影响。我们讨论了基因与环境的相互作用,受表观遗传机制的影响,可能特别是介导的压力反应(本身严重牵连的精神分裂症的出现)。接下来,我们讨论了这个框架对青少年遗传风险人群的合理相关性,这是一个以令人烦恼和难以解释的异质性为特征的风险群体。然后,我们讨论了如何探索表观遗传学和脑网络功能障碍(在风险人群中的一个强有力的验证发现)之间的关系,可以提高压力,表观遗传学和功能神经生物学之间的关系的理解,以及这种关系的相关性,最终出现精神分裂症/精神病。我们认为,这些考虑可以扩大模型的影响,如社会发展认知模型,增加其解释范围。最终,这些研究的整合可能会加强早期识别,干预和治疗青少年精神分裂症的风险。
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.
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