School of Medicine Publications and Presentations
Brain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes
Document Type
Article
Publication Date
5-31-2025
Abstract
Background and Hypothesis
The brain age gap (BAG) quantifies the difference between predicted brain age and chronological age. Prior research implicates higher BAG in psychotic disorders, suggesting accelerated brain aging. We hypothesized distinct brain aging profiles among biological subtypes of psychosis and intermediate BAG in their relatives. Study Design
Brain age gap values were quantified in 348 healthy controls (HCs), 950 psychosis probands classified by both DSM diagnoses of psychotic bipolar disorder, type I (BP, n = 247), schizoaffective disorder (SAD, n = 313), and schizophrenia (SZ, n = 390), and Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Biotypes (301 Biotype 1, 304 Biotype 2, and 345 Biotype 3), and 491 of their non-psychotic first-degree relatives. We calculated brain age values from structural T1-weighted images using the pre-trained, open-source brain age package, brainageR. In probands, we assessed associations between BAG and clinical characteristics, comorbid disorders, medications, and polygenic risk scores for SZ (PRS-SZ). Study Results
All DSM diagnosis and Biotype groups had higher BAG than HC. While no significant differences were observed between BP, SAD, or SZ, Biotypes 1 and 2 had significantly higher BAG compared to Biotype 3. Relatives exhibited intermediate BAG values between HC and probands, with the highest BAG in relatives of those with SAD. Brain age gap was not linked to comorbid disorders or PRS-SZ, but was associated with symptom severity, cognition, functioning, and psychotropic medication use. Conclusions
Bipolar-Schizophrenia Network for Intermediate Phenotypes Biotypes better captured age-related brain structural differences in psychosis than DSM diagnoses. Associations between BAG and medication underscore the potential influence of pharmacotherapy on brain aging in psychosis.
Recommended Citation
Promet, L., Meda, S. A., Alliey-Rodriguez, N., Clementz, B. A., Gershon, E. S., Hill, S. K., Ivleva, E. I., Keedy, S. K., Keshavan, M. S., McDowell, J. E., Parker, D. A., Tamminga, C. A., & Pearlson, G. D. (2025). Brain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes. Schizophrenia bulletin, sbaf022. Advance online publication. https://doi.org/10.1093/schbul/sbaf022
Publication Title
Schizophrenia bulletin
DOI
10.1093/schbul/sbaf022
Academic Level
faculty
Mentor/PI Department
Neuroscience
Comments
© The Author(s) 2025. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. Delayed openaccess.