# Increased Brain-Age Gap in Young Adults With Psychotic Experiences

## TL;DR

Young adults with psychotic experiences have brains that appear older at age 20, but this difference disappears by age 30, suggesting temporary changes in brain development.

## Contribution

This study is the first to show a temporary brain-age gap in young adults with psychotic experiences using longitudinal MRI data.

## Key findings

- At age 20, individuals with psychotic experiences had a larger brain-age gap than controls.
- The brain-age gap was not significantly different at age 30.
- The brain-age gap showed a trend-level association with the severity of psychotic experiences at age 20.

## Abstract

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, R2 = 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.

Some young people occasionally hear, see, or believe things that others do not—so-called psychotic experiences. We asked whether their brains follow an abnormal developmental path. Using standard MRI scans from the ALSPAC birth cohort, we trained a computer model to estimate brain age and compared 20-year-old individuals with and without these experiences, and we rescanned many of them 10 years later. At age 20, those with psychotic experiences showed subtle signs of altered neurodevelopment, but by age 30, the difference had disappeared. The work suggests early, possibly temporary, changes in brain maturation linked to psychotic experiences.

Some young people occasionally hear, see, or believe things that others do not—so-called psychotic experiences. We asked whether their brains follow an abnormal developmental path. Using standard MRI scans from the ALSPAC birth cohort, we trained a computer model to estimate brain age and compared 20-year-old individuals with and without these experiences, and we rescanned many of them 10 years later. At age 20, those with psychotic experiences showed subtle signs of altered neurodevelopment, but by age 30, the difference had disappeared. The work suggests early, possibly temporary, changes in brain maturation linked to psychotic experiences.