Evidence of discontinuity between psychosis-risk and non-clinical samples in the neuroanatomical correlates of social function

Objective: Social dysfunction is a major feature of clinical-high-risk states for psychosis (CHR-P). Prior research has identified a neuroanatomical pattern associated with impaired social function outcome in CHR-P. The aim of the current study was to test whether social dysfunction in CHR-P is neurobiologically distinct or in a continuum with the lower end of the normal distribution of individual differences in social functioning. Methods: We used a machine learning classifier to test for the presence of a previously validated brain structural pattern associated with impaired social outcome in CHR-P (CHR-outcome-neurosignature) in the neuroimaging profiles of individuals from two non-clinical samples (total n = 1763) and examined its association with social function, psychopathology and cognition. Results: Although the CHR-outcome-neurosignature could be detected in a subset of the non-clinical samples, it was not associated was adverse social outcomes or higher psychopathology levels. However, participants whose neuroanatomical profiles were highly aligned with the CHR-outcome-neurosignature manifested subtle disadvantage in fluid (PFDR = 0.004) and crystallized intelligence (PFDR = 0.01), cognitive flexibility (PFDR = 0.02), inhibitory control (PFDR = 0.01), working memory (PFDR = 0.0005), and processing speed (PFDR = 0.04). Conclusions: We provide evidence of divergence in brain structural underpinnings of social dysfunction derived from a psychosis-risk enriched population when applied to non-clinical samples. This approach appears promising in identifying brain mechanisms bound to psychosis through comparisons of patient populations to nonclinical samples with the same neuroanatomical profiles.

Automated summary

This study investigated whether social dysfunction in individuals at clinical high risk for psychosis is distinct from the lower end of the normal distribution of social functioning. The findings suggest that there are divergent brain structural underpinnings of social dysfunction in clinical and non-clinical samples. Although the neuroanatomical pattern associated with impaired social function outcome was found in some non-clinical samples, it was not associated with adverse social outcomes or higher levels of psychopathology. However, participants whose neuroanatomical profiles aligned more closely with the pattern showed subtle disadvantages in cognitive functioning.