Prospective Studies of Neurodevelopmental Influences in Schizophrenia

Department of Psychiatry, University of Pennsylvania,

associated with an increased risk for schizophrenia, but the

mechanism(s) involved and whether their influences depend on,

covary with, or are independent of genetic risk are unclear. We

examined markers of fetal hypoxia and other OCs as predictors of

adult psychiatric outcome in a cohort of 9,110 individuals (194

schizophrenics, 135 non-schizophrenic siblings, 895 psychiatric

controls, and 7,886 non-psychiatric controls) born in

Philadelphia from 1959 to 1966, whose gestations and births were

monitored prospectively with standard research protocols.

Psychiatric diagnoses were ascertained via adult treatment

contracts. The odds of schizophrenia increased linearly, while

the odds of being an unaffected sibling of a schizophrenic

decreased linearly, with increasing number of hypoxia-associated

OC’s. This effect was also present when modeling odds of

schizophrenia within families. There was no relationship between

these OCs and other psychiatric disorders, and there were no

associations between other (prenatal or perinatal) complications

and schizophrenia. Together with results from our neuroimaging

studies conducted in Scandinavia, these findings support the

notion that a genetic factor in schizophrenia may confer a

heightened susceptibility to the pathogenic effects of fetal

oxygen deprivation, and argue against models in which OCs result

from genetic predisposition to schizophrenia or increase risk for