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bioRxiv · 10.1101/2025.01.09.631642

Social dysfunction relates to altered default mode network functional integrity across neuropsychiatric disorders: A replication and generalization study

Braak, S.·Mennes, M.·Su, T.·Pijnenburg, Y. A. L.·Bakker, G.·Arango, C.·van der Wee, N.·Bauduin, S.·Moya, A. O.-T.·Lopez-Morinigo, J.-D.·Dawson, G. R.·Abrahams, A. B.·Beckenstrom, A. C.·Beckmann, C. F.·Marston, H. M.·Penninx, B. W. J. H.·Kas, M. J. H.
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Abstract

BackgroundSocial dysfunction is an early manifestation of neuropsychiatric disorders that may relate to altered Default Mode Network (DMN) integrity. This study aimed to replicate previous findings linking social dysfunction with diminished resting-state DMN functional connectivity and altered task-based DMN functional activation in response to emotional faces across schizophrenia (SZ), Alzheimers disease (AD), and healthy controls (HC), and to extend these findings to major depressive disorder (MDD). MethodsResting-state fMRI and task-based fMRI data on implicit facial emotional processing were acquired in an overlapping cohort (resting-state fMRI: N=167; SZ=32, MDD=44, AD=29, HC=62. Task-based fMRI: N=152; SZ=30, MDD=42, AD=26, HC=54). Additionally, mega-analyses (N=317 for resting-state fMRI; N=291 for task-based fMRI) of the current and a prior independent sample were conducted. Social dysfunction was indexed with the Social Functioning Scale (SFS) and the De Jong-Gierveld Loneliness (LON) scale. ResultsThe association between higher mean SFS+LON social dysfunction scores and diminished DMN connectivity within the dorsomedial prefrontal cortex across SZ/AD/HC participants was replicated, and extended to MDD patients. Similar observations within the dorsomedial and rostromedial prefrontal cortex were found in the mega-analysis. Associations between social dysfunction and DMN activation in response to sad and happy faces were not replicated or found in the mega-analysis. ConclusionsDiminished dorsomedial prefrontal cortex DMN connectivity emerged as a transdiagnostic neurobiological marker for social dysfunction, suggesting a potential treatment target for precision medicine approaches. DMN functional responses to emotional faces may not be a sensitive biomarker for social dysfunction.

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Braak, S., Mennes, M., Su, T., Pijnenburg, Y. A. L., Bakker, G., Arango, C., van der Wee, N., Bauduin, S., Moya, A. O.-T., Lopez-Morinigo, J.-D., Dawson, G. R., Abrahams, A. B., Beckenstrom, A. C., Beckmann, C. F., Marston, H. M., Penninx, B. W. J. H., Kas, M. J. H.. 2025-01-10. Social dysfunction relates to altered default mode network functional integrity across neuropsychiatric disorders: A replication and generalization study. https://doi.org/10.1101/2025.01.09.631642

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