A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia

In this study, me examined whether fetal hypoxia and other obstetric compli cations (OCs) are related to risk for adult schizophrenia; whether such eff ects are specific to cases with an early age at onset; and whether the obst etric influences depend on, covary with, or are independent of familial ris k, Subjects were 72 patients with schizophrenia or schizoaffective disorder ; 63 of their siblings not diagnosed with schizophrenia; and 7,941 nonpsych iatric controls, whose gestations and births were monitored prospectively w ith standard research protocols as part of the National Collaborative Perin atal Project. Adult psychiatric morbidity was ascertained via a longitudina l treatment data base indexing regional public health service utilization, and diagnoses were made by review of all pertinent medical records accordin g to DSM-IV criteria, We found that the odds of schizophrenia increased lin early with increasing number of hypoxia-associated OCs and that this effect was specific to cases with an early age at onset/first treatment contact. There were no relationships between schizophrenia and birth weight or other (prenatal/nonhypoxic) OCs, Siblings of patients with schizophrenia were no more likely to have suffered hypoxia-associated OCs than were nonpsychiatr ic cohort controls, Because the majority of individuals exposed to fetal hy poxia did not develop schizophrenia, such factors likely are incapable of c ausing schizophrenia on their own, Together, these findings suggest that hy poxia acts additively or interactively with genetic factors in influencing liability to schizophrenia. We propose a model in which the neurotoxic effe cts of fetal hypoxia may lead to an earlier onset of psychosis because of p remature pruning of cortical synapses.