Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty.

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TitleDimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty.
Publication TypeJournal Article
Year of Publication2016
AuthorsSatterthwaite, TD, Cook, PA, Bruce, SE, Conway, C, Mikkelsen, E, Satchell, E, Vandekar, SN, Durbin, T, Shinohara, RT, Sheline, YI
JournalMol Psychiatry
Date Published2016 07
KeywordsAdult, Amygdala, Anxiety, Anxiety Disorders, Cerebral Cortex, Connectome, Depression, Depressive Disorder, Major, Female, Functional Neuroimaging, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Middle Aged, Neural Pathways, Prefrontal Cortex, Stress Disorders, Post-Traumatic

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.

Alternate JournalMol Psychiatry
PubMed ID26416545
PubMed Central IDPMC4840084
Grant ListK24 MH079510 / MH / NIMH NIH HHS / United States
K23 MH098130 / MH / NIMH NIH HHS / United States
RC1 MH089704 / MH / NIMH NIH HHS / United States
R01 MH064821 / MH / NIMH NIH HHS / United States
R01 NS085211 / NS / NINDS NIH HHS / United States
R01 MH107703 / MH / NIMH NIH HHS / United States
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