Summary: Adolescents at elevated risk for developing psychosis show subtle differences in brain structure, including reduced cortical thickness compared with peers without risk factors. Among those who later developed psychosis, cortical thinning was most pronounced in several temporal and frontal brain regions.
Source: University of Pittsburgh
Adolescents with a higher likelihood of developing psychosis exhibit subtle, measurable differences in brain anatomy, according to an international collaboration led by neuroscientists at the University of Pittsburgh School of Medicine and Maastricht University.
Published in JAMA Psychiatry, the study pooled the largest collection of structural magnetic resonance imaging (MRI) scans to date for young people assessed as being at clinical high risk for psychosis. Although the group-level differences are clear and statistically significant, they are too subtle to serve as individual diagnostic markers. Still, these findings contribute to ongoing efforts to build cumulative risk models that could support earlier detection, targeted care, and new prevention strategies.
The data set combined scans and clinical information from 3,169 volunteers recruited across 31 institutions, with an average participant age of 21. About half of the participants—1,792 individuals—were classified as being at clinical high risk for developing psychosis. Of those high-risk participants, 253 developed psychosis within two years of assessment. The scale of the pooled sample—reported by the study authors as including roughly 600% more high-risk youth who transitioned to psychosis than any earlier single study—made it possible to detect small but reliable differences in brain structure.
Co-chairs of the ENIGMA Clinical High Risk for Psychosis Working Group, Maria Jalbrzikowski, Ph.D., assistant professor of psychiatry at the University of Pittsburgh, and Dennis Hernaus, Ph.D., assistant professor at the School of Mental Health and Neuroscience at Maastricht University, emphasize that the observed effects are modest and currently not applicable for individual diagnosis. “Our sample size gave us the statistical power to identify consistent brain changes associated with later psychosis, but the overlap between groups is still large,” Jalbrzikowski explained. “At present, these brain measures cannot predict outcomes for single patients.”
Across the combined scans, participants identified as clinically high risk showed widespread reductions in cortical thickness—a measure of the brain’s gray matter—compared with control participants. Those individuals who later developed psychosis had the most pronounced thinning in several temporal and frontal regions. Although cortical thinning is a normal part of development from adolescence to adulthood, the pattern and timing differed in the high-risk group.
Notably, among the younger subset of participants (ages 12 to 16) who later transitioned to psychosis, cortical thinning was already detectable and appeared to advance more slowly than in the control group. The authors suggest this may reflect developmental processes that begin earlier in life and only become clinically relevant during the adolescent period—a time of both opportunity and vulnerability as the brain undergoes major maturation.
Psychosis encompasses a range of severe mental health conditions marked by hallucinations, delusions, and impaired reality testing. Schizophrenia is one disorder associated with psychosis, but psychotic symptoms can also occur in mood disorders such as bipolar disorder and major depression, as well as in post-traumatic stress disorder and other psychiatric conditions. Outcomes vary widely among people who experience psychosis, underscoring the need for better early detection and individualized treatment strategies.
Hernaus noted that these results point to the value of longitudinal research: “Most previous studies examined brain differences at a single time point. Tracking brain changes over time will be critical for understanding the mechanisms that lead from early risk to the onset of psychosis and for identifying windows for intervention.”
The study was made possible through the collaborative efforts of more than 100 researchers participating in the ENIGMA Clinical High Risk for Psychosis Working Group. The full list of contributors and detailed methods appear in the JAMA Psychiatry manuscript.
Funding: This research received support from multiple funders listed in the JAMA Psychiatry manuscript. Maria Jalbrzikowski received support from the National Institute of Mental Health under grant K01 MH112774.
About this psychosis research news
Source: University of Pittsburgh
Contact: Allison Hydzik, University of Pittsburgh
Image: The image is in the public domain
Original Research: The research appears in JAMA Psychiatry