Neural correlates of stress-related gene-environment interactions

虽然基因-环境相互作用(GxE)的研究有望为复杂疾病的病因学提供重要线索，但目前精神病学中GxE应用于分类疾病表型的证据仍不确定。为了充分发挥其潜力，将GxE研究与神经科学领域相结合可能会提供一个强有力的策略。在拟议的项目中，我们的目标是研究选定的候选基因和发育过程中的环境逆境对对压力特别敏感的神经网络的联合影响。在一项流行病学队列研究中，200名年轻人从出生起就被跟踪研究，他们将接受磁共振成像和功能磁共振成像结合脑电检查，以评估参与情绪调节和奖励处理的大脑区域的形态和功能。作为候选基因，我们将研究与5-羟色胺和多巴胺信号有关的功能变异。作为候选环境条件，产前逆境将与早期产后逆境和青春期生活逆境进行对比。识别GxE在应激敏感神经网络中的潜在机制将有助于建立更有效的诊断、预防和治疗应激相关疾病的方法。

Although the study of gene-environment interactions (GxE) promises to provide important clues as to the etiology of complex disorders, current evidence of GxE in psychiatry applied to categorical disease phenotypes remains inconclusive. In order to fulfill its potential, an integration of GxE research with the field of neuroscience may provide a powerful strategy. In the proposed project, we aim to study the joint effects of selected candidate genes and environmental adversities during development on neural networks that are particularly sensitive to stress. In 200 young adults from an epidemiological cohort study followed since birth, MRI and fMRI combined with EEG will be performed to assess the morphology and function of brain regions involved in emotion regulation and reward processing. As candidate genes, functional variants implicated in serotonin and dopamine signaling will be examined. As candidate environmental conditions, prenatal adversities will be contrasted with early postnatal and adolescent life adversities. Identification of mechanisms underlying GxE in stress-sensitive neural networks will help to establish more effective ways of diagnosing, preventing and treating stress-related disorders.