Brain development in adolescents at ultra-high risk for psychosis: Longitudinal changes related to resilience

The main focus of studies of individuals at ultra-high risk for psychosis (UHR) has been on identifying brain changes in those individuals who will develop psychosis. However, longitudinal studies have shown that up to half of UHR individuals are resilient, with symptomatic remission and good functioning at follow-up. Yet little is known about brain development in resilient individuals. Therefore, the aim of this study was to investigate differences in brain development between resilient and non-resilient individuals.

A six-year longitudinal structural MRI study was performed with up to three scans per individual. The final sample consisted of 48 UHR individuals and 48 typically developing controls with a total of 225 MRI-scans, aged 12-20 years at the time of the first MRI-scan and matched for age, gender and number of follow-up scans. At six-year follow-up, 35 UHR individuals were divided in resilient (good functional outcome) and non-resilient (poor functional outcome) subgroups, defined by the modified Global Assessment of Functioning. The main outcome measures were developmental changes in MR-based measures of cortical and subcortical anatomy.

We found widespread differences in volume of frontal, temporal and parietal cortex between resilient and non-resilient individuals. These were already present at baseline and remained stable over development (12-24 years). Furthermore, there were differences in the development of cortical surface area in frontal regions including cingulate gyrus.

Developmental differences may reflect compensatory neural mechanisms, where better functioning in resilient individuals leads to less tissue loss over development.