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Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis
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OBJECT: Mild traumatic brain injury (TBI) has been proposed as a risk factor for the development of Alzheimer’s disease, Parkinson’s disease, depression, and other illnesses. This study’s objective was to determine the association of prior mild TBI with the subsequent diagnosis (that is, at least 1 year postinjury) of neurological or psychiatric disease. METHODS: All studies from January 1995 to February 2012 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, study references, and review articles. Reviewers abstracted the data and assessed study designs and characteristics. RESULTS: Fifty-seven studies met the inclusion criteria. A random effects meta-analysis revealed a significant association of prior TBI with subsequent neurological and psychiatric diagnoses. The pooled odds ratio (OR) for the development of any illness subsequent to prior TBI was 1.67 (95% CI 1.44–1.93, p < 0.0001). Prior TBI was independently associated with both neurological (OR 1.55, 95% CI 1.31–1.83, p < 0.0001) and psychiatric (OR 2.00, 95% CI 1.50–2.66, p < 0.0001) outcomes. Analyses of individual diagnoses revealed higher odds of Alzheimer’s disease, Parkinson’s disease, mild cognitive impairment, depression, mixed affective disorders, and bipolar disorder in individuals with previous TBI as compared to those without TBI. This association was present when examining only studies of mild TBI and when considering the influence of study design and characteristics. Analysis of a subset of studies demonstrated no evidence that multiple TBIs were associated with higher odds of disease than a single TBI. CONCLUSIONS: History of TBI, including mild TBI, is associated with the development of neurological and psychiatric illness. This finding indicates that either TBI is a risk factor for heterogeneous pathological processes or that TBI may contribute to a common pathological mechanism.
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“TBI is associated with a number of deleterious outcomes, with meta-analytic evidence pro viding a link for the sub sequent development of neurological and psychiatric disorders. 6”
From Traumatic brain injury in homeless and marginally housed individuals: a systematic review and meta-analysis (2020) · cites this paper as [6]
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Milillo, M. M., Neumann, C. S., Maurer, J., Jin, C., Commerce, E., Reynolds, B., Harenski, C. L., & Kiehl, K. A. (2024) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-024-01212-x · Cited by 2
Pebole, M. M., Iverson, K. M., Bolduc, C. M., Joyce, J. M., Sablone, C. A., & Fortier, C. B. (2024) · Brain Sciences · doi:10.3390/brainsci14080814 · Cited by 3
Eliasen, M., Petersen, J., Benros, M. E., & Osler, M. (2021) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13347 · Cited by 3
Hiraoka, T. (2019) · Neurocase · doi:10.1080/13554794.2019.1599026 · Cited by 3
Frankot, M. A., O’Hearn, C. M., & Haar, C. V. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112879 · Cited by 3
Wehn, A. C., Khalin, I., Hu, S., Harapan, B. N., Mao, X., Cheng, S., Plesnila, N., & Terpolilli, N. A. (2024) · Journal of Neurotrauma · doi:10.1089/neu.2024.0042 · Cited by 2
Patel, H., Nooner, K. B., Reich, J. C., Woodley, M. M. O., Cummins, K. M., & Brown, S. A. (2024) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2024.101427 · Cited by 2
A population-based cohort study of perinatal mental illness following traumatic brain injury
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Zhang, S., Afshar, H. T., Colvonen, P. J., Nokes, B. T., Compton, J. N., Mishra, J., Bismark, A. W., Ramanathan, D., & Koloski, M. F. (2025) · CNS Drugs · doi:10.1007/s40263-025-01180-w · Cited by 2
Martindale, S. L., O’Connor, V. L., Walker, W. C., Bailie, J. M., Allen, C. M., Pastorek, N. J., Tate, D. F., Wilde, E. A., & Rowland, J. A. (2025) · Archives of Physical Medicine and Rehabilitation · doi:10.1016/j.apmr.2025.04.009 · Cited by 2
Traumatic Brain Injury Induced Chronic Pain Syndrome
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Associations Between Mental Disorders and Risk of Mild Cognitive Impairment
Lee, Y. J., Kim, H., Jung, J.-H., Han, K., & Jeon, H. J. (2025) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0000000000001863 · Cited by 2
Metadata
- Authors
- Perry, D. C., Sturm, V. E., Peterson, M. J., Pieper, C. F., Bullock, T., Boeve, B. F., Miller, B. L., Guskiewicz, K. M., Berger, M. S., Kramer, J. H., & Welsh-Bohmer, K. A.
- Affiliations
- Pediatrics and Genetics (US)
- University of California, San Francisco (US)
- United States Department of Veterans Affairs (US)
- Biostatistics and Bioinformatics, and
- Mayo Clinic (US)
- University of North Carolina at Chapel Hill (US)
- Neurosurgery;
- Duke University (US)
- ORCID
- Venue
- Journal of Neurosurgery
- Published
- 2016-02
- Volume
- 124
- Issue
- 2
- Pages
- 511-526
- ISSN
- 0022-3085 (ISSN-L)
- 1933-0693
- PMC
- PMC4751029
- OpenAlex
- W2130029062
- Cited by
- 440
- References
- 107
- Citations by year
- 2026: 33 · 2025: 43 · 2024: 46 · 2023: 51 · 2022: 29 · 2021: 48 · 2020: 68 · 2019: 46 · 2018: 31 · 2017: 28 · 2016: 16
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of neurosurgery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1km1ca156687-01, AG016574)
- National Institute on Aging (P30 AG28377, P30AG028377, U01AG006786, K23AG040127, R01AG041797, P50AG1657303, R01AG032306, K23AG045289, P01AG019724, P50AG023501, P50AG016574)
- National Cancer Institute (KM1-CA156687)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
- Keywords
- mild traumatic brain injury, Alzheimer's disease, Parkinson's disease, depression, bipolar disorder, mild cognitive impairment, risk factors
- MeSH terms
- Mental Disorders, Brain Concussion, Brain Injuries, Dementia, Humans, Nervous System Diseases, Risk Factors
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