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Neurocognitive endophenotypes of obsessive compulsive disorder and their brain correlates

强迫症的神经认知内表型及其大脑相关性

基本信息

批准号：
249236207
负责人：
Professor Dr. Norbert Kathmann
金额：
--
依托单位：
Institut für Psychologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/249236207?language=en
关键词：
Neurocognitive endophenotypes obsessive compulsive disorder

项目摘要

The causes for obsessive-compulsive disorder (OCD) are insufficiently known. This is probably due to the limited etiological validity of the clinical-phenomenological description of the disorder. Despite strong evidencefor heritability of obsessive-compulsive traits and disorder in twin and family studies only weak associations with gene variants have been established so far. Endophenotypes (EPT) for mental disorders are quantitativebiological or cognitive traits that are closer to the biological underpinnings than the clinical syndrome itself. Therefore, they are expected to make the search for relevant genes more efficient, to facilitate the detection of interacting psychological factors, and, generally, to foster the development of better pathogenetic models and better therapies. At present, there is highly promising evidence for three EPT candidates for OCD. Those are 1. Event-related brain potential correlates of action monitoring, 2. Saccadic indicators of endogenuous action initiation, and 3. behavioral indicators of motor response inhibition. However, these EPT candidates have been confirmed in small sample studies only, and their relation to symptom dimensions and subtypes of OCD as well as to their neural underpinnings remains unclear as yet. We plan to further analyse the three candidates using an adequately large sample, in order to a) confirm them as reliable EPTs of OCD, b) relate them specifically to OCD symptom dimensions and age at disease onset, and c) test the relationship of the EPT candidates to structural and functional brain measures. As a future perspective, associations of confirmed EPT variables with candidate gene variants will be tested, and longitudinal studies focusing on the effects of EPTs will be conducted. In the present project, we aim to compare 200 patients with OCD, 200 first-degree relatives of OCD patients, and 200 healthy comparison subjects. A main strength of the present approach is its reexamination and extension of relevant findings with sufficient power and the integration into a coherent model. The present project will be conducted in two research centers (Berlin, Bonn), is based on promising and substantial pilot studies and combines the research and methodological expertise of the two contributing research groups.

强迫症（OCD）的病因还不清楚。这可能是由于有限的病因有效性的临床现象学描述的障碍。尽管在双胞胎和家族研究中有强有力的证据表明强迫症的特征和障碍具有遗传性，但到目前为止，只建立了与基因变异的弱关联.精神障碍的内表型（EPT）是指比临床症状本身更接近生物学基础的定量生物学或认知特征。因此，它们有望使相关基因的搜索更有效，以促进相互作用的心理因素的检测，并在一般情况下，促进更好的发病模型和更好的治疗方法的发展。目前，有非常有希望的证据表明，有三种EPT候选人患有强迫症。这些是1。动作监测的事件相关脑电位相关性，2。扫视指标的内源性行动启动，和3。运动反应抑制的行为指标。然而，这些EPT候选者仅在小样本研究中得到证实，其与强迫症的症状维度和亚型以及其神经基础的关系尚不清楚。我们计划使用足够大的样本进一步分析这三个候选者，以便a）确认它们是OCD的可靠EPT，B）将它们与OCD症状维度和疾病发作时的年龄具体相关，以及c）测试EPT候选者与结构和功能脑测量的关系。作为未来的展望，将测试已确认的EPT变量与候选基因变体的关联，并将进行侧重于EPT影响的纵向研究。在本项目中，我们的目的是比较200名强迫症患者，200名强迫症患者的一级亲属，和200名健康对照组。本方法的一个主要优点是，它重新审查和扩展了具有足够效力的相关研究结果，并将其纳入一个连贯的模型。本项目将在两个研究中心（柏林、波恩）进行，以有前途的大量试点研究为基础，并结合两个提供投入的研究小组的研究和方法专门知识。