Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology.
Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology.
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DOI：
10.1002/da.22633
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发表时间：
2017-07
影响因子：
7.4
通讯作者：
Miller MW
中科院分区：
文献类型：
--
作者：
Miller DR;Logue MW;Wolf EJ;Maniates H;Robinson ME;Hayes JP;Stone A;Schichman S;McGlinchey RE;Milberg WP;Miller MW
越来越多的证据表明，创伤后应激障碍（PTSD）与默认模式网络（DMN）连接中断有关，但研究结果并不一致。相关基因的个体差异可能解释了DMN连接和PTSD之间关系的一些报道的变异性。在这项研究中，我们调查了这种可能性，使用全基因组关联研究（GWAS）衍生的多基因风险评分（PRS）的相关精神病特征。我们假设，PTSD和DMN连接之间的关联将被一个或多个精神病特征的遗传风险所调节，这样，精神病理学和严重PTSD的多基因风险升高的个体将表现出DMN连接中断。参与者是156名白色非西班牙裔伊拉克和阿富汗战争退伍军人，他们进行了基因分型，并接受了静息状态功能磁共振成像和临床评估。使用已发布的基于大型联盟的GWAS的汇总统计数据计算了神经质、焦虑、重度抑郁症和交叉障碍风险（基于五种精神疾病）的PRS。交叉障碍多基因风险影响DMN连接和PTSD症状严重程度之间的关系，例如，个体在更大的遗传风险表现出显着的负相关PTSD症状严重程度和连接之间的后扣带皮层和右颞中回。神经质、焦虑和重性抑郁障碍的多基因风险并不直接或通过与PTSD的相互作用影响DMN连接。研究结果说明了全基因组PRS的潜在力量，以促进对PTSD和DMN连接之间关系的理解，这是一种假定的神经内表型的疾病。
Accumulating evidence suggests that posttraumatic stress disorder (PTSD) is associated with disrupted default mode network (DMN) connectivity, but findings across studies have not been uniform. Individual differences in relevant genes may account for some of the reported variability in the relationship between DMN connectivity and PTSD. In this study, we investigated this possibility using genome-wide association study (GWAS)-derived polygenic risk scores (PRSs) for relevant psychiatric traits. We hypothesized that the association between PTSD and DMN connectivity would be moderated by genetic risk for one or more psychiatric traits such that individuals with elevated polygenic risk for psychopathology and severe PTSD would exhibit disrupted DMN connectivity. Participants were 156 white, non-Hispanic Veterans of the wars in Iraq and Afghanistan who were genotyped and underwent resting state functional magnetic resonance imaging and clinical assessment. PRSs for neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based on five psychiatric disorders) were calculated using summary statistics from published large-scale consortia-based GWASs. Cross-disorder polygenic risk influenced the relationship between DMN connectivity and PTSD symptom severity such that individuals at greater genetic risk showed a significant negative association between PTSD symptom severity and connectivity between the posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for neuroticism, anxiety, and major depressive disorder did not influence DMN connectivity directly or through an interaction with PTSD. Findings illustrate the potential power of genome-wide PRSs to advance understanding of the relationship between PTSD and DMN connectivity, a putative neural endophenotype of the disorder.
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影响因子：
10.6
作者：
Amaral, DG
通讯作者：
Amaral, DG
影响因子：
3.7
作者：
Buhle, Jason T.;Silvers, Jennifer A.;Ochsner, Kevin N.
通讯作者：
Ochsner, Kevin N.
影响因子：
12.8
作者：
Cisler JM;Koster EH
通讯作者：
Koster EH
影响因子：
1.7
作者：
Canli, T;Desmond, JE;Gabrieli, JDE
通讯作者：
Gabrieli, JDE
DOI：
10.3758/cabn.10.1.141
发表时间：
2010-03
期刊：
Cognitive, affective & behavioral neuroscience
影响因子：
--
作者：
Engels AS;Heller W;Spielberg JM;Warren SL;Sutton BP;Banich MT;Miller GA
通讯作者：
Miller GA