Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders
Open accessAbstract
Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders.
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MDD has been associated with neuroanatomic/neurodevelopmental as well as brain transcriptome evidence of accelerated brain aging.
“Further, MDD has been associated with neuroanatomic/neurodevelopmental as well as brain transcriptome evidence of accelerated brain aging (Douillard-Guilloux et al., 2013; Koutsouleris et al., 2014).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Koutsouleris et al., 2014
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- Authors
- Koutsouleris, N., Davatzikos, C., Borgwardt, S., Gaser, C., Bottlender, R., Frodl, T., Falkai, P., Riecher-Rossler, A., Moller, H.-J., Reiser, M., Pantelis, C., & Meisenzahl, E.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- University of Pennsylvania (US)
- University of Basel (CH)
- The University of Melbourne (AU)
- Corresponding author
- Koutsouleris, N.
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-13
- Volume
- 40
- Issue
- 5
- Pages
- 1140-1153
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC4133663
- OpenAlex
- W2167579130
- Cited by
- 448
- References
- 51
- Citations by year
- 2026: 31 · 2025: 42 · 2024: 46 · 2023: 50 · 2022: 41 · 2021: 55 · 2020: 44 · 2019: 34 · 2018: 29 · 2017: 29 · 2016: 20 · 2015: 15 · 2014: 9 · 2013: 1
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Bulletin (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- edoc (University of Basel)
- Funders
- National Institute on Aging (R01AG021910, P50AG005681, P01AG003991)
- National Institute of Mental Health (P50MH071616, R01MH056584)
- National Center for Research Resources (U24RR021382)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- accelerated brain aging, schizophrenia
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aging, Borderline Personality Disorder, Brain, Major Depressive Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Psychotic Disorders, Risk, Schizophrenia, Biomarkers, Age of Onset, Disease Progression, Young Adult
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