特异性双相障碍和精神分裂症情感认知神经环路损害以及易感基因对此环路的影响

Emerging data in bipolar disorder (BD) and schizophrenia (SZ) simultaneously support overlapping susceptibility to genes that regulate the development of frontotemporal neural systems as well as features of frontotemporal abnormalities that are distinct to each disorder. Specifically, previous work has yielded findings of that frontotemporal neural system abnormalities in BD are centered in more ventral structures including ventral prefrontal cortex (VPFC) and amygdala, while deficits in more dorsal areas are implicated in SZ including dorsal lateral prefrontal cortex (DLPFC) and the hippocampus. And，mounting evidence in genetic imaging studiess implicate that genetic factors influences the frontotemporal neural system in both BD and SZ, result in different distributions of neural abnormalities with a ventral concentration in BD and a dorsal focus in SZ. Our proposed work will use multimodal neuroimaging techniques and molecular genetics to develop an interdisciplinary model for the effects of genetic variation on the disparate neuropathophysiologies of BD and SZ via direct comparison of these disorders. As the first study, integration of multimodality neuroimaging and molecular genetics can have important translational implications and possibly lead to improved understanding of the mechanisms that contribute to the differential development of frontotemporal neural circuitry abnormalities underlying BD and SZ..Besides the improvement in identification of patients with BD and SZ, it can provide a valuable basis for investigating treatment strategies by elucidating molecular mechanisms as targets for the development of novel and more effective treatments. These potential contributions would greatly advance the psychiatric field and the medical management of psychiatric disorders.

双相情感障碍(BD)和精神分裂症(SZ)存在极为相似的情感认知损害和执行此功能的皮质边缘系统神经环路的损害，以及相似的遗传易感基因。由于这些相似性，造成了两种疾病及时和正确诊治的困难。本课题组前期多模态影像学工作证实了BD的皮质边缘系统损害多集中于腹侧结构[腹侧前额叶和杏仁核]；而背侧区域的缺损则与SZ有关[背侧前额叶，海马和杏仁核]。影像遗传学研究提示BD和SZ的易感基因通过不同的作用通路或作用于皮质边缘系统不同的组分导致了BD和SZ在此神经环路的不同损害。但目前尚无利用多模态影像遗传学技术对两者同时进行比较研究的报道。为此，本课题拟利用多模态影像学和分子遗传学技术对BD和SZ进行直接比较，试图建立遗传介导的BD和SZ皮质边缘系统影像遗传学跨学科模型。这将有助于深入了解皮质边缘系统执行情感认知功能的分子生物学机制，揭示BD和SZ不同的病理生理机制，为两种疾病的诊治提供可靠的依据。

精神分裂症(SZ)和双相障碍(BD)存在极为相似的情感认知损害和执行此功能的皮质边缘系统神经环路的损害，以及相似的遗传易感基因。由于这些相似性，造成了两种疾病早期和正确诊治的困难。项目负责人所在的课题组通过多模态影像学技术直接对比SZ和BD两种疾病的这一神经环路，发现了这两种疾病存在着相似性和特异性的损害。另外课题组的另一项研究结果显示BD和重性抑郁障碍（MDD）也存在着类似的影像学变化。这些结果均揭示了SZ、BD和MDD可能具有同源属性以及各自特异性的损害。为了更加深入的研究这一科学问题，课题组利用影像学技术对三种疾病的前额叶-杏仁核神经环路进行了直接比较研究，明确了三种疾病前额叶-杏仁核皮质边缘系统神经环路功能连接的特异性改变，为三种疾病的临床诊断和精准治疗提供了影像学依据，为建立基于生物学标志的精神疾病分类体系提供科学依据。