Premature Brain Aging and Choroid Plexus Enlargement in Young Adults with Psychosis
Neslihan Yildiz-Ozhan1, Jarrett Rushmore2, Suheyla Cetin-Karayumak1, Yogesh Rathi1, Michael J. Coleman1, Slyvain Bouix1, Tashrif Billah1, Si Gao3, Bhim M. Adhikari3, Peter Kochunov3, Cornelius Berberich4, Ofer Pasternak1, Daphne J. Holt1, Matcheri S. Keshavan1, Dost Ongur1, Alan Breier5, Martha E. Shenton1, Marek Kubicki1, Johanna Seitz-Holland1
1Harvard Medical School, 2Boston University, 3University of Texas Health Science, 4Technical University of Munich, 5Indiana University
Objective:
A higher-than-expected rate of cerebral aging has been reported in individuals with neuropsychiatric disorders, but remains poorly understood. We aimed to investigate whether a premature brain aging phenotype exists in young individuals with psychosis.
Background:
The Regional Vulnerability Index for Alzheimer’s Disease (RVI-AD) quantifies how closely an individual’s brain resembles Alzheimer’s-like aging patterns, providing a biomarker of structural aging. The choroid plexus (ChP), a cerebrospinal fluid (CSF)–producing and immune-regulating structure, enlarges with age and has been linked to neurodegenerative conditions. Both RVI-AD and ChP morphology are linked to biological aging in healthy and neurodegenerative populations; however, their relevance to psychosis remains unexplored. Investigating these associations may clarify how immune–CSF alterations are related to brain aging patterns in early psychosis.
Design/Methods:
T1-weighted 3T MRI data from 60 participants (ages 17–36; 47 psychosis spectrum, 13 controls) from the Human Connectome Project for Early Psychosis dataset were analyzed. ChP volumes were manually segmented (inter-rater ICC = 0.87), adjusted for intracranial volume, and standardized into z-scores. Linear regression models were used to (1) compare groups on RVI-AD and ChP volume and (2) examine associations between ChP volume and AD-RVI within the psychosis group, adjusting for age, sex, socioeconomic status, and site.
Results:
Participants with psychosis demonstrated significantly higher RVI-AD (β = 0.79, p = 0.02) than controls, consistent with age-related brain patterns, with no ChP volume differences. Within the psychosis group, greater ChP volume was positively associated with higher RVI-AD (β = 0.40, p = 0.003).
Conclusions:
Individuals with psychosis exhibited increased age-related structural brain signatures, observed already in early adulthood. The positive association between RVI-AD and ChP volumes likely suggests overlapping immune and structural processes contributing to premature brain aging. Ongoing analyses in an expanded cohort (n = 120) with inflammatory and clinical measures will further explore neuroimmune pathways in early aging trajectories of psychosis.
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