Childhood head injury and expression of schizophrenia in multiply affected families

BACKGROUND: The etiology of schizophrenia is believed to include genetic and nongenetic factors, with the pathogenesis involving abnormal neurodevelopment. We investigated whether mild head injury during brain maturation plays a role in the expression of schizophrenia in multiply affected families. METHODS: We compared the history and severity of head injuries in childhood (age, < or =10 years) and through adolescence (age, < or =17 years) in 67 subjects with narrowly defined schizophrenia and 102 of their unaffected siblings from 23 multiply affected families. In subjects with schizophrenia, only head injuries preceding the onset of psychosis were considered. RESULTS: Subjects in the schizophrenia group (n = 16 [23.9%]) were more likely than the unaffected siblings group (n = 12 [11.8%]) to have a history of childhood head injury (P =.04; odds ratio, 2.35 [95% confidence interval, 1.03-5.36]). Subjects in the schizophrenia group with a history of childhood head injury had a significantly younger median age at onset of psychosis (20 years) compared with those with no such history (25 years; z = -2.98; P =.003). The severity of head injury ranged from minimal to mild, including concussions, but within this narrow range, severity was correlated with younger age at onset (r(s) = -0.66; P =.005). Head injury occurred a median of 12 years before the onset of psychosis. Results were similar if head injuries during adolescence were included, but did not achieve statistical significance. CONCLUSIONS: Mild childhood head injury may play a role in the expression of schizophrenia in families with a strong genetic predisposition. Prospective studies of mild head injury should consider genetic predisposition for possible long-term neurobehavioral sequelae.