Social dysfunction is transdiagnostically associated with default mode network dysconnectivity in schizophrenia and Alzheimer’s disease
The World Journal of Biological Psychiatry, vol. 23, pp. 264–277
Abstract
Objectives Social dysfunction is one of the most common signs of major neuropsychiatric disorders. The Default Mode Network (DMN) is crucially implicated in both psychopathology and social dysfunction, although the transdiagnostic properties of social dysfunction remains unknown. As part of the pan-European PRISM (Psychiatric Ratings using Intermediate Stratified Markers) project, we explored cross-disorder impact of social dysfunction on DMN connectivity.Methods We studied DMN intrinsic functional connectivity in relation to social dysfunction by applying Independent Component Analysis and Dual Regression on resting-state fMRI data, among schizophrenia (SZ; N = 48), Alzheimer disease (AD; N = 47) patients and healthy controls (HC; N = 55). Social dysfunction was operationalised via the Social Functioning Scale (SFS) and De Jong-Gierveld Loneliness Scale (LON).Results Both SFS and LON were independently associated with diminished DMN connectional integrity within rostromedial prefrontal DMN subterritories (pcorrected range = 0.02–0.04). The combined effect of these indicators (Mean.SFS + LON) on diminished DMN connectivity was even more pronounced (both spatially and statistically), independent of diagnostic status, and not confounded by key clinical or sociodemographic effects, comprising large sections of rostromedial and dorsomedial prefrontal cortex (pcorrected=0.01).Conclusions These findings pinpoint DMN connectional alterations as putative transdiagnostic endophenotypes for social dysfunction and could aid personalised care initiatives grounded in social behaviour.
Authors 17
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Ilja M. J. Saris corresponding
Amsterdam Neuroscience · Amsterdam Public Health · GGZ inGeest · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam UMC, VU Medical Centre and GGZ inGeest, Amsterdam, The Netherlands
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Leiden University · Amsterdam Neuroscience · Amsterdam Public Health · GGZ inGeest · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam UMC, VU Medical Centre and GGZ inGeest, Amsterdam, The Netherlands
Institute of Education and Child Studies, Section Forensic Family and Youth Care, Leiden University, Leiden, The Netherlands
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
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Amsterdam Neuroscience · Amsterdam University Medical Centers · Vrije Universiteit Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands
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Nic J.A. van der Wee Aachen Department of Psychiatry, Leiden University Medical Centre Leiden Institute for Brain and Cognition
Leiden University · Leiden University Medical Center
Affiliation as printed
Department of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands
Leiden Institute for Brain and Cognition, Leiden, The Netherlands
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Affiliation as printed
P1vital Ltd, Wallingford, UK
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Affiliation as printed
P1vital Ltd, Wallingford, UK
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Affiliation as printed
P1vital Ltd, Wallingford, UK
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Affiliation as printed
SBGneuro Ltd, Oxford, UK
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University Medical Center Groningen · University of Groningen
Affiliation as printed
Department of Biomedical Sciences of Cells and Systems, Cognitive Neurosciences, University of Groningen, University Medical Center of Groningen, Groningen, The Netherlands
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Universidad Complutense de Madrid · Hospital General Universitario Gregorio Marañón · Centro de Investigación Biomédica en Red de Salud Mental
Affiliation as printed
Centre of Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
Hospital General Universitario Gregorio Marañón, CIBERSAM, IiSGM, Universidad Complutense, School of Medicine, Madrid, Spain
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Centro de Investigación Biomédica en Red de Salud Mental · Hospital Universitario de La Princesa · Universidad Autónoma de Madrid
Affiliation as printed
Centre of Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
Department of Psychiatry, La Princesa University Hospital, Universidad Autonoma de Madrid, Marid, Spain
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Affiliation as printed
P1vital Ltd, Wallingford, UK
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Boehringer Ingelheim (Germany) · Eli Lilly (United Kingdom)
Affiliation as printed
CNS Diseases Research, Boehringer Ingelheim GmbH and Company, Biberach, Germany
Translational Neuroscience, Eli Lilly and Company, Windlesham, UK
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Affiliation as printed
Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands
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Amsterdam Neuroscience · Amsterdam Public Health · GGZ inGeest · Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam UMC, VU Medical Centre and GGZ inGeest, Amsterdam, The Netherlands
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