基于MRI多模态成像技术的抗抑郁治疗对抑郁症自杀行为的机制研究

Depression is a common mental disorders, which always has a much higher suicidal rate and caused great harm and brings about serious economic burden to family and society. Antidepressants have an remarkable curative effect on depression. The rapid development of neuroimaging techniques promotes the understanding of the neural mechanism of drug effect. However, since the neural mechanism of treatment of suicide behavior in depression is nor clear yet, the treatment and prevention of suicide attempt lack theoretical basis. In previous study, we firstly evaluated the white matter integrity in depression suicide attempters, and found that the suiciders have typical whiter matter abnormalities and impaired neural circuitry, suggest that the depression suiciders have a different neuropathologic basis than pure depression. The result has been published in Am J Psychiatry (Impact factor: 14.72) and J Psychiatry Neurosci (Impact factor: 7.49), etc. with the applicant Zhiyun Jia as the first author. Based on our previous study, we plan to conduct multimodality imaging techniques, such as diffusion tensor imaging (DTI) and fMRI resting state functional imaging, to further examine the structure and resting state functional changes in depression with suicide attempts before and after antidepressant treatment, which may reveal the potential neurobiological and pathogenesis mechanism underline the suicide in depression and the treatment mechanism for antidepressant, and guide the prevention and treatment of depressive suicidality.

抑郁症是一种常见的精神障碍性疾病，常伴有较高的自杀率，给家庭和社会带来严重的负担。抗抑郁药对于抑郁症有着明显疗效，而神经影像技术的快速发展对理解药物作用机理起到重要作用。但目前抑郁症自杀行为治疗的神经作用机制尚不清楚，使得抑郁症自杀的治疗和预防缺乏理论基础。在前期工作中，我们首次发现抑郁症自杀未遂者有特征性脑白质结构受损及神经环路的异常，提示抑郁症伴自杀未遂有着和单纯抑郁症不同的神经病理学基础。研究结果发表在Am J Psychiatry (IF=14.72)和J Psychiatry Neurosci (IF=7.49)等知名学术期刊上，为本项目开展奠定了基础。在此基础上，本项目拟联合弥散张量成像和静息态fMRI功能成像等多模成像技术，进一步研究抑郁症自杀者抗抑郁治疗前后大脑结构和静息态功能改变，探索抑郁症自杀行为的神经病理学机制和药物作用机理，为抑郁症自杀行为的预防和治疗提供新的思路。

抑郁症是一种常见的精神障碍性疾病，常伴有较高的自杀率，给家庭和社会带来严重的负担。项目通过四年实施，整合分析所纳入的首发抑郁症和抑郁症治疗后出现药物抵抗或合并焦虑导致抑郁症自杀率上升的发生发展规律，研究了大脑结构、功能和网络改变及其与临床量表评分间的关系，探讨了抑郁症及其亚型发病的神经病理学机制，主要取得以下成果：（1）发现抑郁药物抵抗机制很可能与脑任务积极网络和默认网络间的拮抗关系失衡有关，为难治性抑郁症治疗研究提供了潜在的靶区；（2）发现伴有焦虑的抑郁症在情绪调节和感觉处理相关脑区出现特异性灰质体积增加，为区别这一特殊抑郁症亚型提供了潜在的生物学标志，也为研究通过改善抑郁症焦虑症状，降低抑郁症自杀风险的发生机制奠定了基础；（3）发现首发抑郁症多个与情绪调节有关的脑区存在显著且稳定的灰质体积减小，还发现额叶-边缘系统灰质结构异常是首发抑郁症脑结构改变的基本特征，且与抑郁症高自杀风险相关。发现首发未用药的抑郁症在疾病早期顶叶和枕叶灰质微结构改变，且先于灰质体积降低，有助于理解抑郁症早期发生的神经生物学机制；（4）发现双相情感障碍和双相障碍I型的灰质异常主要位于前额叶皮层和岛叶，双相情感障碍在完成执行功能任务期间始终表现出皮质-纹状体系统异常激活，这可能是其执行能力尤其是反应抑制受损的标志。. 在该基金资助下，项目负责人以第一或通讯作者发表22篇论文（SCI17篇，中科院期刊分区一区4篇，二区8篇，累计影响因子（IF）>78，其中5篇IF>5，3篇IF>8），还有3-4篇待发表。副主编或参编专著4部，获得华夏医学科技一等奖，四川省科技进步一等奖和中华医学科技进步一等奖各1项。还获得四川大学“五粮春医学奖”，“四川省学术和技术带头人”，“四川省卫生健康委学术技术带头人”和“四川省卫生健康领军人才”称号，项目执行期间晋升了教授。依托本项目，共培养博士研究生4名，硕士研究生4名。