Social dysfunction and default mode network functional integrity in neuropsychiatric disorders: A cross-disorder replication and generalization study
European Neuropsychopharmacology, vol. 110, pp. 112847
Abstract
• This study was specifically designed to replicate and generalize findings from the PRISM1 project. • A link between reduced default mode network (DMN) intrinsic functional connectivity and social dysfunction across schizophrenia, Alzheimer’s disease, and healthy control participants was replicated. • This association extended to major depressive disorder patients. • Relations between DMN activation in response to emotional face stimuli and social dysfunction were not replicated. • Altered DMN functional connectivity is a cross-disorder treatment target for social dysfunction. Cross-disorder research and replication of neuroimaging findings remains scarce. Social dysfunction is an early manifestation across diverse 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), Alzheimer’s disease (AD), and healthy controls (HC), and to extend these findings to major depressive disorder (MDD). Resting-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. The 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. To conclude, diminished 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.
Authors 17
-
Simon Braak corresponding
Amsterdam Neuroscience · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, location Vrije Universiteit Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress and Neurodegeneration programs, Amsterdam, the Netherlands. Electronic address: s.braak@amsterdamumc.nl
-
Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, the Netherlands
-
Amsterdam Neuroscience · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, location Vrije Universiteit Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress and Neurodegeneration programs, Amsterdam, the Netherlands
-
Amsterdam Neuroscience · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, the Netherlands; Amsterdam Neuroscience, Neurodegeneration, Amsterdam, the Netherlands
-
Affiliation as printed
Amacrine Scientific Consulting, Amsterdam, the Netherlands
-
Hospital Universitario La Paz · Centro de Investigación Biomédica en Red de Salud Mental · Hospital La Paz Institute for Health Research · Universidad Autónoma de Madrid
Affiliation as printed
Department of Psychiatry, Hospital Universitario La Paz, IdiPAZ, CIBERSAM, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
-
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Medical Centre, Department of Psychiatry, the Netherlands
-
Leiden University · Leiden University Medical Center
Affiliation as printed
Leiden University Medical Centre, Department of Psychiatry, the Netherlands
-
Instituto de Salud Carlos III · Centro de Investigación Biomédica en Red de Salud Mental · Universidad Autónoma de Madrid
Affiliation as printed
Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, Madrid, Spain; Department of Psychiatry, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
-
Universidad Complutense de Madrid · Hospital General Universitario Gregorio Marañón · Centro de Investigación Biomédica en Red de Salud Mental · Instituto de Investigación Sanitaria Gregorio Marañón
Affiliation as printed
Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, School of Medicine, Universidad Complutense, Madrid, Spain
-
Affiliation as printed
P1vital Ltd. Manor House, Howbery Park, Wallingford, United Kingdom
-
Affiliation as printed
P1vital Ltd. Manor House, Howbery Park, Wallingford, United Kingdom
-
Affiliation as printed
P1vital Products Ltd. Manor House, Howbery Park, Wallingford, United Kingdom
-
Radboud University Nijmegen · Donders Institute for Brain, Cognition and Behaviour
Affiliation as printed
Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, the Netherlands
-
Boehringer Ingelheim (Germany)
Affiliation as printed
Boehringer Ingelheim Pharma, Biberach, Germany
-
Amsterdam Neuroscience · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, location Vrije Universiteit Amsterdam, Department of Psychiatry, Boelelaan 1117, Amsterdam, the Netherlands; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress and Neurodegeneration programs, Amsterdam, the Netherlands
-
Affiliation as printed
Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands
Cited by 0 stored of 0
No patents citing this paper on Lens.org (checked 2026-10-11).