精神分裂症的发生、发展可能涉及皮质边缘系统神经发育的易感因素与保护因素的交互作用，但其病理生理机制不清。精神分裂症患者的子女（遗传高危人群）的精神分裂症患病率远高于普通人群，但部分患者子女由于遗传易感性所致早年脑发育异常可随着脑发育而正常化，提示高危人群虽然具有遗传易感因素，同时还可能携带保护因素，以抵抗其遗传易感性所致的脑损害。因此进行首发未用药精神分裂症患者和遗传高危人群的比较研究将为识别精神分裂症的易感因素和保护因素以及它们的相互作用机制提供重要手段。本项目拟在前期工作的基础上，应用多模态磁共振影像学和分子遗传学的研究手段，对首发未用药精神分裂症和遗传高危人群的皮质边缘系统神经环路进行比较研究，探讨其与易感基因多态性的相关性，试图揭示精神分裂症发病的皮质边缘系统神经环路的病理生理机制以及保护性生物学机制，最终为精神分裂症的早期诊断和有效治疗提供可靠的依据。

The onset and development of schizophrenia (SZ) is related with the interaction between neural and molecular genetic features for vulnerability and resilience on the neurodevelopment of the cortico-limbic neural system. As of yet, neuropathophysiological mechanisms underlying schizophrenia remain unknown. The lifetime risk to SZ in genetic high risk for SZ (GHR-SZ, offspring of one parent with SZ) is much higher than the general population; however, the evidence of normalizing the early abnormalities in their late time and the majority of this population will not develop the disorder in their lifetime, suggests that the GHR-SZ study could detect genetic vulnerability as well as resilient features. The study of medicated naïve first episode schizophrenia (FE-SZ) and GHR-SZ provides a unique opportunity to address the important questions on identifying important features of vulnerability and resilience to SZ and how they interplay. In this proposed study, we will apply multimodality neuroimaging to examine the distinct patterns in structural and functional connectivity in the cortico-limbic neural system in a unique population including medication naïve FE-SZ, GHR-SZ and healthy control participants. We will also explore effects of genetic variations on this neural system in order to elucidate the genetic mechanism of neural system alterations in the disorder. The proposed work could make important contributions to the understanding of neuropathophysiology of SZ neurodevelopment and identifying neural and molecular genetic features for vulnerability and resilience in SZ, and ultimately benefit the early protection, diagnosis and treatment.