Brain correlates of cognitive reserve in offspring of patients with schizophrenia or bipolar disorder

Cognitive reserve (CR) modulates the impact of neural alterations on clinical outcomes, yet its association with brain structure during youth remains unexplored. We aimed to investigate the relationship between CR and brain structure in young offspring of patients with schizophrenia or bipolar disorder, according to development of psychotic spectrum symptoms over time. 404 data acquisitions were analyzed from offspring of patients with schizophrenia or bipolar disorder, 43 offspring who developed psychotic spectrum symptoms over time (SzBpO-P), 94 offspring who did not (SzBpO-NP), and 80 community controls (CcO), re-assessed over a 12-year period (101 SzBpO-P, 181 SzBpO-NP, 122 CcO). Global and lobar volume, cortical surface area and thickness metrics were obtained from T1-weighted sequences acquired on a 3 Tesla MRI scanner and computed using FreeSurfer version 7.1. CR was calculated using a composite score including an estimated intelligence quotient, sociability, parental socioeconomic status, school performance, and developmental milestones. Multilevel mixed-effect logistic regression (categorical variables) or linear regression (continuous variables) models were conducted. A significant group-by-CR interaction was found for total intracranial volume (F = 7.770; p < 0.001), whereby the CcO and SzBpO-NP groups showed a positive association between CR and total intracranial volume, while this association was negative for SzBpO-P. No significant effects were observed in other brain structural metrics when adjusting for total intracranial volume. CR was differentially associated with total intracranial volume according to development of psychotic spectrum symptoms. These results may help identify youth at highest risk for severe mental health outcomes.