Accelerated brain aging associated with executive deficits in adolescence and early adulthood among individuals with schizophrenia and genetic high risk

Abnormal brain development and cognitive function are present in adolescence and early adulthood of schizophrenia (SZ). However, it is still unclear whether these developmental abnormalities and cognitive deficits occur in adolescence and early adulthood in individuals at genetic high risk (GHR). This study aims to examine brain age gap differences during adolescence and early adulthood in individuals with SZ, GHR, and healthy control (HC), as well as their associations with cognitive function. This study recruited a total of 240 subjects aged between 12 and 25, comprising 83 SZ, 48 GHR, and 109 HC. We calculated all participants’ brain age gap using their structural MRI. The subtests of Wisconsin Card Sorting Test were utilized to evaluate executive function. Compared to HC group, both GHR group ( P = .021) and SZ ( P < .001) group showed greater brain age gap (brain age > chronological age). Notably, within GHR group, greater brain age gap was associated with higher non-perseverative errors in executive function ( r= .39, P FDR = 0.035), whereas in SZ group, it was correlated with higher perseverative errors ( r= .35, P FDR = 0.005). This study suggests that changes in brain age during adolescence and early adulthood in SZ and GHR individuals may reflect disease’s genetic susceptibility. A greater brain age gap may be associated with the onset and progression of executive deficits in SZ.