title: Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Satterthwaite
authors.affiliation: Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Cook
authors.affiliation: Department of Psychology, University of Missouri-St. Louis, St. Louis, MO, USA.|Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Bruce
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: C
authors.initials: C
authors.lastname: Conway
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Mikkelsen
authors.affiliation: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Satchell
authors.affiliation: Departments of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: S N
authors.initials: SN
authors.lastname: Vandekar
authors.affiliation: Department of Psychiatry, Washington University, St. Louis, MO, USA.
authors.forename: T
authors.initials: T
authors.lastname: Durbin
authors.affiliation: Departments of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Shinohara
authors.affiliation: 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.
authors.forename: Y I
authors.initials: YI
authors.lastname: Sheline
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism / Q000503:physiopathology; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology; D001008:Anxiety Disorders / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology; D063132:Connectome / Q000379:methods / Q000706:statistics & numerical data*; D003863:Depression / Q000378:metabolism / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000503:physiopathology*