Neurofunctional aberrations associated with social cognition across clinical and genetic risk groups for schizophrenia: a meta-analysis of fMRI studies

Aberrant social cognition is a core feature of schizophrenia, persisting from clinical high-risk and genetic high-risk states to the first episode of psychosis. This study aimed to identify shared and distinct social cognition-related functional alterations across clinical high-risk, genetic high-risk, and first episode of psychosis groups, shedding light on varying risk levels for first episode of psychosis development. Meta-analyses were performed on 38 whole-brain task-based functional magnetic resonance imaging studies (12 clinical high risk, 15 genetic high risk, 11 first episode of psychosis) using Seed-based d Mapping. Function abnormalities were assessed within each patient group, with quantitative comparisons made against controls. Clinical high-risk and genetic high-risk individuals showed neither shared nor distinct abnormal brain activation during social cognition tasks. A shared cluster of increased activation in the right anterior cingulate cortex was observed between genetic high-risk and first episode of psychosis groups. However, no conjunction or disjunction results were found between clinical high-risk and first episode of psychosis groups. Meta-regression analyses revealed accelerated age-related greater activation decline in the left insula in individuals with clinical high risk. In conclusion, the absence of shared social cognition-related brain activation between clinical high risk and genetic high risk may signify differences in neural correlates underlying social cognition deficits between these groups and they follow distinct neural pathways toward first episode of psychosis. The shared abnormal anterior cingulate cortex activation in genetic high risk and first episode of psychosis may represent an endophenotype of schizophrenia.