Is traumatic brain injury a risk factor for schizophrenia? A meta-analysis of case-controlled population-based studies.

Charlene Molloy, Royal College of Surgeons in Ireland
Ronán M. Conroy, Royal College of Surgeons in Ireland
David R. Cotter, Royal College of Surgeons in Ireland
Mary Cannon, Royal College of Surgeons in Ireland

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Traumatic brain injury (TBI) is known to lead to a range of adverse psychiatric sequelae but the question of whether TBI is a risk factor for psychosis and, in particular, schizophrenia remains unclear. Studies examining this issue have yielded conflicting results. We carried out a systematic review of the literature on TBI and psychosis in order to identify all population-based controlled studies which provide estimates of risk for schizophrenia following TBI. Odds ratios (ORs) were combined using random effects meta-analysis. Our literature search yielded 172 studies which were considered to be potentially relevant. From these, we identified 9 studies that could provide estimates of risk in the form of ORs. The pooled analysis revealed a significant association between TBI and schizophrenia (OR = 1.65; 95% CI = 1.17-2.32), with significant heterogeneity between the studies. Estimates from the family studies (OR = 2.8: 95% CI =1.76-4.47) were higher than those from the cohort/nested case-control studies (OR = 1.42: 95% CI = 1.02-1.97) by a factor of almost 2. There did not appear to be a dose-response relationship between severity of head injury and subsequent risk of schizophrenia. This meta-analysis supports an increased risk of schizophrenia following TBI, with a larger effect in those with a genetic predisposition to psychosis. Further epidemiological and neuroscientific studies to elucidate the mechanisms underlying this association are warranted.