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

Molecular Psychiatry volume 21, pages 894–902 (2016)Cite this article

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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.

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Authors and Affiliations

  1. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    T D Satterthwaite, E Mikkelsen, E Satchell & Y I Sheline

  2. Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    P A Cook & Y I Sheline

  3. Department of Psychology, University of Missouri–St. Louis, St. Louis, MO, USA

    S E Bruce

  4. Department of Psychiatry, Washington University, St. Louis, MO, USA

    S E Bruce, C Conway & T Durbin

  5. Departments of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    S N Vandekar & R T Shinohara

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  1. T D Satterthwaite
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Correspondence to Y I Sheline.

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Competing interests

CC was previously on the speaker’s bureau for Bristol-Myers Squibb and Otsuka Pharmaceuticals and has received research funding from Bristol-Myers Squibb, Cyberonics, the Stanley Baer Foundation, the Brain and Behavior Research Foundation and the Taylor Foundation for Innovative Psychiatric Research. He serves as a non-paid consultant to Cyberonics. Remaining authors declare no conflict of interest.

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Satterthwaite, T., Cook, P., Bruce, S. et al. Dimensional depression severity in women with major depression and post-traumatic stress disorder correlates with fronto-amygdalar hypoconnectivty. Mol Psychiatry 21, 894–902 (2016). https://doi.org/10.1038/mp.2015.149

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