ON THE NATURE AND MECHANISMS OF OBSTETRIC INFLUENCES IN SCHIZOPHRENIA- A REVIEW AND SYNTHESIS OF EPIDEMIOLOGIC STUDIES

Obstetric complications are robust correlates of schizophrenia, but it remains controversial whether more than one neurally-disruptive mecha nism is involved and whether such influences covary with, depend on, o r are independent of the disorder's genetic basis. Labor and delivery complications (LDCs), particularly perinatal hypoxia, are the most con sistently-replicated obstetric correlates of schizophrenia and appear as risk factors in a larger proportion of cases than pregnancy complic ations (including viral exposure) and signs of fetal maldevelopment. H owever, the vast majority of individuals exposed to such LDCs, even in the extreme, do not develop schizophrenia, indicating that they are u nlikely to cause the disorder on their own. In addition, unaffected si blings and offspring of schizophrenics are no more likely to have a hi story of LDCs than are unaffected individuals from the general populat ion, indicating that such factors are not likely to be caused by genet ic predisposition to the disorder. Findings from prospective studies o f high-risk samples and representative birth cohorts are consistent in showing that the association of LDCs with schizophrenia (and with sev erity of its neuropathological features) is greater among those with a n elevated genetic risk, suggesting that predisposing genes for schizo phrenia may confer a heightened susceptibility of the fetal brain to t he neurotoxic consequences of oxygen deprivation (and, possibly, other obstetric mechanisms). These findings encourage the search for candid ate genes that mediate the brain's vulnerability to hypoxic-ischemic n euronal injury and suggest the use of preventive obstetric practices i n high-risk pregnancies.