Social dysfunction relates to shifts within socioaffective brain systems among Schizophrenia and Alzheimer's disease patients

•Social dysfunction is present in both schizophrenia and Alzheimer's disease patients.•More social dysfunction related to neural hyperactivity in response to sad faces.•More social dysfunction related to neural hypoactivity in response to happy faces.•These effects were independent of diagnosis.•These findings could aid personalized care initiatives grounded in social behaviour. Social dysfunction represents one of the most common signs of neuropsychiatric disorders, such as Schizophrenia (SZ) and Alzheimer's disease (AD). Perturbed socioaffective neural processing is crucially implicated in SZ/AD and generally linked to social dysfunction. Yet, transdiagnostic properties of social dysfunction and its neurobiological underpinnings remain unknown. As part of the European PRISM project, we examined whether social dysfunction maps onto shifts within socioaffective brain systems across SZ and AD patients. We probed coupling of social dysfunction with socioaffective neural processing, as indexed by an implicit facial emotional processing fMRI task, across SZ (N = 46), AD (N = 40) and two age-matched healthy control (HC) groups (N = 26 HC-younger and N = 27 HC-older). Behavioural (i.e., social withdrawal, interpersonal dysfunction, diminished prosocial or recreational activity) and subjective (i.e., feelings of loneliness) aspects of social dysfunction were assessed using the Social Functioning Scale and De Jong-Gierveld loneliness questionnaire, respectively. Across SZ/AD/HC participants, more severe behavioural social dysfunction related to hyperactivity within fronto-parieto-limbic brain systems in response to sad emotions (P = 0.0078), along with hypoactivity of these brain systems in response to happy emotions (P = 0.0418). Such relationships were not found for subjective experiences of social dysfunction. These effects were independent of diagnosis, and not confounded by clinical and sociodemographic factors. In conclusion, behavioural aspects of social dysfunction across SZ/AD/HC participants are associated with shifts within fronto-parieto-limbic brain systems. These findings pinpoint altered socioaffective neural processing as a putative marker for social dysfunction, and could aid personalized care initiatives grounded in social behaviour.