Traumatic brain injury and schizophrenia in members of schizophrenia and bipolar disorder pedigrees

Objective: Schizophrenia following a traumatic brain injury could be a phen ocopy of genetic schizophrenia or the consequence of a gene-environment int eraction. Alternatively, traumatic brain injury and schizophrenia could be spuriously associated if those who are predisposed to develop schizophrenia have greater amounts of trauma for other reasons. The authors investigated the relationship between traumatic brain injury and psychiatric diagnoses in a large group of subjects from families with at least two biologically r elated first-degree relatives with schizophrenia, schizoaffective disorder, or bipolar disorder. Method: The Diagnostic Interview for Genetic Studies was used to determine history of traumatic brain injury and diagnosis for 1,275 members of multip lex bipolar disorder pedigrees and 565 members of multiplex schizophrenia p edigrees. Results: Rates of traumatic brain injury were significantly higher for thos e with a diagnosis of schizophrenia, bipolar disorder, and depression than for those with no mental illness. However, multivariate analysis of within- pedigree data showed that mental illness was related to traumatic brain inj ury only in the schizophrenia pedigrees. Independent of diagnoses, family m embers of those with schizophrenia were more likely to have had traumatic b rain injury than were members of the bipolar disorder pedigrees. The member s of the schizophrenia pedigrees also failed to show the gender difference for traumatic brain injury (more common in men than in women) that was expe cted and was present in the bipolar disorder pedigrees. Subjects with a sch izophrenia diagnosis who were members of the bipolar disorder pedigrees lan d thus had less genetic vulnerability to schizophrenia) were less likely to have had traumatic brain injury (4.5%) than were subjects with schizophren ia who were members of the schizophrenia pedigrees land who had greater gen etic vulnerability to schizophrenia) (19.6%). Conclusions: Members of the schizophrenia pedigrees, even those without a s chizophrenia diagnosis, had greater exposure to traumatic brain injury com pared to members of the bipolar disorder pedigrees. Within the schizophreni a pedigrees, traumatic brain injury was associated with a greater risk of s chizophrenia, consistent with synergistic effects between genetic vulnerabi lity for schizophrenia and traumatic brain injury. Posttraumatic-brain-inju ry schizophrenia in mu[tip[ex schizophrenia pedigrees does not appear to be a phenocopy of the genetic disorder.