Impact of genetic vulnerability and hypoxia on overall intelligence by age7 in offspring at high risk for schizophrenia compared with affective psychoses

Risk factors for schizophrenia, such as genetic vulnerability and obstetric complications, have been associated with cognitive deficits in schizophren ia. We tested the association of these risk factors with general intellectu al ability in offspring at high risk for psychoses and normal control subje cts. Offspring of 182 parents with DSM-IV schizophrenia or affective psycho ses were recruited and diagnosed from the Boston and Providence cohorts of the National Collaborative Perinatal Project (NCPP). Control subjects from the NCPP were selected to be comparable with affected parents based on the parent's age, ethnicity, study site, number of offspring enrolled in the NC PP, and payment status, and on the offspring's age, sex, and history of obs tetric complications. Based on data prospectively acquired from pregnancy a nd events of gestation, labor, delivery, and the neonatal period, we derive d a measure of probable hypoxic-ischemic insult. We also report on standard ized measures of general intelligence (intelligence quotient [IQ]) collecte d at age 7. General linear mixed models were used to test for the simultane ous effects of genetic vulnerability, defined as parental diagnosis, and pr obable hypoxic insult on age 7 IQ. Specificity of the effects for schizophr enia compared with affective psychoses and sex effects were also tested. Lo w IQ at age 7 was significantly associated with genetic vulnerability to ps ychoses, in particular with schizophrenia.