Abstract

Traumatic brain injury (TBI) is associated with schizophrenia, but the causal nature of this relationship is not clear. Three models for their association exist: 1) TBI causes a phenocopy of schizophrenia (parallelism); 2) TBI is a marker of schizophrenia vulnerability (spurious association); and 3) TBI interacts with genetic vulnerability to cause schizophrenia (interaction or effect modification). We found that TBI is a causal component of some cases of schizophrenia, specifically those with enhanced genetic vulnerability. This has biological plausibility. Prevention of 50% of these cases could lead to a savings of $313 million annually in the United States. Further research on critical windows for traumatic brain injury in vulnerable individuals could shed light on the developmental pathophysiology of schizophrenia.

Keywords: Traumatic brain injury, schizophrenia, prevention, gene-environment interaction, risk