title: A prospective cohort study of genetic and perinatal influences in the etiology of schizophrenia.
abstract: In this study, we examined whether fetal hypoxia and other obstetric complications (OCs) are related to risk for adult schizophrenia; whether such effects are specific to cases with an early age at onset; and whether the obstetric influences depend on, covary with, or are independent of familial risk. Subjects were 72 patients with schizophrenia or schizoaffective disorder; 63 of their siblings not diagnosed with schizophrenia; and 7,941 nonpsychiatric controls, whose gestations and births were monitored prospectively with standard research protocols as part of the National Collaborative Perinatal Project. Adult psychiatric morbidity was ascertained via a longitudinal treatment data base indexing regional public health service utilization, and diagnoses were made by review of all pertinent medical records according to DSM-IV criteria. We found that the odds of schizophrenia increased linearly 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 nonpsychiatric cohort controls. Because the majority of individuals exposed to fetal hypoxia did not develop schizophrenia, such factors likely are incapable of causing schizophrenia on their own. Together, these findings suggest that hypoxia acts additively or interactively with genetic factors in influencing liability to schizophrenia. We propose a model in which the neurotoxic effects of fetal hypoxia may lead to an earlier onset of psychosis because of premature pruning of cortical synapses.
authors.affiliation: Department of Psychology, University of California, Los Angeles 90095-1563, USA. cannon@psych.ucla.edu
authors.forename: T D
authors.initials: TD
authors.lastname: Cannon
authors.forename: I M
authors.initials: IM
authors.lastname: Rosso
authors.forename: J M
authors.initials: JM
authors.lastname: Hollister
authors.forename: C E
authors.initials: CE
authors.lastname: Bearden
authors.forename: L E
authors.initials: LE
authors.lastname: Sanchez
authors.forename: T
authors.initials: T
authors.lastname: Hadley
mesh_terms: D000328:Adult; D017668:Age of Onset; D001720:Birth Injuries / Q000150:complications*; D001724:Birth Weight; D002540:Cerebral Cortex / Q000648:ultrastructure; D005260:Female; D005311:Fetal Hypoxia / Q000150:complications*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018570:Risk Assessment; D012559:Schizophrenia / Q000209:etiology* / Q000235:genetics*