Satterthwaite T D, Cook P A, Bruce S E, Conway C, Mikkelsen E, Satchell E, Vandekar S N, Durbin T, Shinohara R T, Sheline Y I
Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Mol Psychiatry. 2016 Jul;21(7):894-902. doi: 10.1038/mp.2015.149. Epub 2015 Sep 29.
Depressive symptoms are common in multiple psychiatric disorders and are frequent sequelae of trauma. A dimensional conceptualization of depression suggests that symptoms should be associated with a continuum of deficits in specific neural circuits. However, most prior investigations of abnormalities in functional connectivity have typically focused on a single diagnostic category using hypothesis-driven seed-based analyses. Here, using a sample of 105 adult female participants from three diagnostic groups (healthy controls, n=17; major depression, n=38; and post-traumatic stress disorder, n=50), we examine the dimensional relationship between resting-state functional dysconnectivity and severity of depressive symptoms across diagnostic categories using a data-driven analysis (multivariate distance-based matrix regression). This connectome-wide analysis identified foci of dysconnectivity associated with depression severity in the bilateral amygdala. Follow-up seed analyses using subject-specific amygdala segmentations revealed that depression severity was associated with amygdalo-frontal hypo-connectivity in a network of regions including bilateral dorsolateral prefrontal cortex, anterior cingulate and anterior insula. In contrast, anxiety was associated with elevated connectivity between the amygdala and the ventromedial prefrontal cortex. Taken together, these results emphasize the centrality of the amygdala in the pathophysiology of depressive symptoms, and suggest that dissociable patterns of amygdalo-frontal dysconnectivity are a critical neurobiological feature across clinical diagnostic categories.
抑郁症状在多种精神疾病中很常见，并且是创伤后的常见后遗症。抑郁症的维度概念表明，症状应与特定神经回路中连续的功能缺陷相关。然而，大多数先前关于功能连接异常的研究通常使用基于假设的种子分析，集中在单一诊断类别上。在此，我们以来自三个诊断组的105名成年女性参与者为样本（健康对照组，n = 17；重度抑郁症组，n = 38；创伤后应激障碍组，n = 50），使用数据驱动分析（基于多元距离的矩阵回归）研究静息态功能连接障碍与不同诊断类别中抑郁症状严重程度之间的维度关系。这种全脑连接组分析确定了双侧杏仁核中与抑郁严重程度相关的连接障碍焦点。使用个体特异性杏仁核分割的后续种子分析表明，抑郁严重程度与包括双侧背外侧前额叶皮层、前扣带回和前岛叶在内的区域网络中的杏仁核 - 额叶低连接性相关。相比之下，焦虑与杏仁核和腹内侧前额叶皮层之间的连接性升高有关。综上所述，这些结果强调了杏仁核在抑郁症状病理生理学中的核心地位，并表明可分离的杏仁核 - 额叶连接障碍模式是跨临床诊断类别的关键神经生物学特征。
