Pediatric traumatic brain injury as a risk factor for psychosis and psychotic symptoms: A systematic review and meta-analysis

Abstract

Background Psychosis is one of the most disabling psychiatric disorders. Pediatric traumatic brain injury (pTBI) has been cited as a developmental risk factor for psychosis, however this association has never been assessed meta-analytically. Methods A systematic review and meta-analysis of the association between pTBI and subsequent psychotic disorders/symptoms was performed. The study was pre-registered (CRD42022360772) adopting a random-effects model to estimate meta-analytic odds ratio (OR) and 95% confidence interval (CI) using the Paule-Mandel estimator. Subgroup (study location, study design, psychotic disorder v. subthreshold symptoms, assessment type, and adult v. adolescent onset) and meta-regression (quality of evidence) analyses were also performed. The robustness of findings was assessed through sensitivity analyses. The meta-analysis is available online as a computational notebook with an open dataset. Results We identified 10 relevant studies and eight were included in the meta-analysis. Based on a pooled sample size of 479686, the pooled OR for the association between pTBI and psychosis outcomes was 1.80 (95% CI 1.11-2.95). There were no subgroup effects and no outliers. Both psychotic disorder and subthreshold symptoms were associated with pTBI. The overall association remained robust after removal of low-quality studies, however the OR reduced to 1.43 (95% CI 1.04-1.98). A leave-one-out sensitivity analysis showed the association was robust to removal of all but one study which changed the estimate to marginally non-significant. Conclusions We report cautious meta-analytic evidence for a positive association between pTBI and future psychosis. New evidence will be key in determining long-term reliability of this finding.