Abstract
Though social functioning is often hampered in Major Depressive Disorder (MDD), we lack a complete and integrated understanding of the underlying neurobiology. Connectional disturbances in the brain’s Default Mode Network (DMN) might be an associated factor, as they could relate to suboptimal social processing. DMN connectional integrity, however, has not been explicitly studied in relation to social dysfunctioning in MDD patients. Applying Independent Component Analysis and Dual Regression on resting-state fMRI data, we explored DMN intrinsic functional connectivity in relation to social dysfunctioning (i.e. composite of loneliness, social disability, small social network) among 74 MDD patients (66.2% female, Mean age = 36.9, SD = 11.9). Categorical analyses examined whether DMN connectivity differs between high and low social dysfunctioning MDD groups, dimensional analyses studied linear associations between social dysfunction and DMN connectivity across MDD patients. Threshold-free cluster enhancement (TFCE) with family-wise error (FWE) correction was used for statistical thresholding and multiple comparisons correction (P < 0.05). The analyses cautiously linked greater social dysfunctioning among MDD patients to diminished DMN connectivity, specifically within the rostromedial prefrontal cortex and posterior superior frontal gyrus. These preliminary findings pinpoint DMN connectional alterations as potentially germane to social dysfunction in MDD, and may as such improve our understanding of the underlying neurobiology.
Highlights
A neurobiological system potentially relevant to both socialfunctioning and Major Depressive Disorder (MDD) pathophysiology is the brain’s Default Mode Network (DMN), which has been shown to play a critical role in various aspects of human social behavior[10,11,12,13,14]
The categorical analyses examined whether DMN connectivity differs between high and low social dysfunction MDD groups, while the dimensional analysis tested whether a linear association can be found between social dysfunction and DMN connectivity across MDD patients
Using the composite social dysfunction score, we examined the association of social dysfunction and DMN connectivity in MDD patients, both categorically and dimensionally
Summary
A neurobiological system potentially relevant to both social (dys)functioning and MDD pathophysiology is the brain’s Default Mode Network (DMN), which has been shown to play a critical role in various aspects of human social behavior[10,11,12,13,14]. In order to cover social functioning more broadly and fully, here we assess the cumulative association of three important social dysfunction indices and DMN connectivity within MDD patients These indices include loneliness, perceived social disability, and small social network; factors present among MDD patients in varying levels and associated with adverse neurobiological changes[11,31,32,33,34,35,36,37,38]. Using this cumulative social dysfunction score, we explored the effect of social dysfunction on DMN whole-network connectivity among MDD patients, both categorically and dimensionally. Post-hoc sensitivity analyses investigated the influence of current comorbid anxiety disorder, antidepressant use, and depression severity on DMN-social dysfunction relationships
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