青春期经前期烦躁症的中国人群遗传变异和脑网络特征研究

Premenstrual Dysphoric Disorder (PMDD) is not uncommon among adolescent female population. PMDD may hamper psychological development and disable social function of the vulnerable minors. Because the etiology is largely unclear for PMDD, clinical diagnosis is essentially dependent on manifestation whereas the treatment plan is not specific and may deteriorate the symptoms. Up-to-date evidence indicate the strong heritability of PMDD, while little data show that sexual hormone change during menstruation may influence brain function. The genetic and brain imaging studies in PMDD are, however, rather lacking. This proposal aims to 1) identify genetic variants for PMDD by sequencing candidate genes including sexual hormones and neuroendocrine transmitters; 2) discover PMDD-associated characteristics of brain network by using functional MRI and diffusion tensor imaging; 3) elucidate the gene - neurobiological mechanism underlying PMDD and provide valid markers for intelligent diagnosis and specific treatment, by coupling analysis of genetic information and brain imaging. Our findings will shed light on the important contributing mechanisms of PMDD and offer potential biological targets for improved diagnosis and treatment.

经前期烦躁症（Premenstrual dysphoric disorder, PMDD）在青春期女性人群中并不罕见，会对患者的心理发育和社会功能造成严重损害。由于PMDD的发病机理尚不明确，目前临床的诊断依赖于症状，治疗药物缺乏特异性且可能加重相关症状。虽然目前有初步研究提示PMDD有较强的遗传背景，少量证据显示月经期性激素可能影响大脑功能，但是整体上尚缺乏PMDD的遗传风险和脑影像学研究。本研究创新性地在中国青春期人群中1）通过测序性激素和神经内分泌基因，探索影响PMDD发病的遗传变异；2）运用功能磁共振和弥散张量成像技术，发现PMDD特异的脑网络特征；3）结合遗传信息和脑影像对PMDD进行多模态研究，阐明PMDD的遗传-神经机制,并为PMDD的智能诊断和特异化治疗寻找标记物。本研究结果将有助于深入理解PMDD的发病机制，为PMDD的诊断和治疗提供潜在的生物靶点。

经前期烦躁症（premenstrual dysphoric disorder, PMDD）在青春期女性人群中并不罕见，会对患者的心理发育和社会功能造成严重损害。由于PMDD的发病机理尚不明确，目前临床的诊断依赖于症状，治疗药物缺乏特异性且可能加重相关症状。虽然目前有初步研究提示PMDD有较强的遗传背景，少量证据显示月经期性激素可能影响大脑功能，但是整体上尚缺乏PMDD的遗传风险和脑影像学研究。本研究创新性地在中国青春期人群中进行表型研究，探索PMDD对中国青春期人群的心理健康的影响，发现PMDD是中国青春期人群女性的焦虑、抑郁、自伤、自杀风险升高的关键因素；也探索PMDD的危险因素，发现校园欺凌会让PMDD的风险增高3倍；还开发了与PMDD相关的经前期综合征的简化版测评工具，采用6道题目就可以较为准确的识别经前期综合征。正在开展研究包括对问卷工具在中国人群中进行验证，在青春期和成年早期人群中收集唾液DNA进行全基因组测序和全基因组关联研究，通过测序性激素和神经内分泌基因，探索影响PMDD发病的遗传变异；也运用功能磁共振和弥散张量成像技术，发现PMDD特异的脑网络特征；后期本课题将结合遗传信息和脑影像对PMDD进行多模态研究，阐明PMDD的遗传-神经机制,并为PMDD的智能诊断和特异化治疗寻找标记物。目前的研究结果有助于从经前期烦躁症的角度探索青少年心理健康的影响因素以及PMDD的发展的高危因素，正在开展的研究结果将有助于深入理解PMDD的发病机制，为PMDD的诊断和治疗提供潜在的生物靶点。