Increased Brain-Age Gap in Young Adults With Psychotic Experiences

Psychotic experiences (hallucinations and delusions: PEs) are linked to structural brain variation, but their relationship to magnetic resonance imaging (MRI)-derived brain age is unclear. We hypothesized that young adults reporting PEs would show an increased brain-age gap (predicted - chronological age) and that this gap would diverge over 10 years.

A multilayer perceptron (2628 training scans; age 6-50 years; mean absolute error = 4.3 years, R ² = 0.72) estimated brain age from T1-weighted MRIs in the ALSPAC (Avon Longitudinal Study of Parents and Children). Participants were scanned at around age 20 years (N = 245; 124 with PEs) and again at around 30 years (N = 279; 69 with PEs); 113 participants contributed both scans. Linear mixed-effects models tested case-control, severity, and time-by-group effects.

At the initial time point, individuals with PEs showed a larger brain-age gap than control individuals (d [95% CI] = 0.70 [0.14 to 1.27]; q = .029). The brain-age gap showed a trend-level association with PE severity (d [95% CI] = 1.32 [0.00 to 2.64]; q = .098). At the follow-up, the group difference was nonsignificant (d [95% CI] = 0.22 [-0.08 to 0.51]; q = .153). No longitudinal case-control divergence reached significance, likely reflecting limited power.

Young adults who report PEs display an older-looking brain in early adulthood, consistent with atypical brain maturation. However, the gap does not clearly widen or contract by age 30. Multimodal, longitudinal cohorts spanning adolescence to midadulthood are needed to map psychosis-related atypical brain maturation.