Impact of genetic vulnerability and hypoxia on overall intelligence by age 7 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 schizophrenia. We tested the association of these risk factors with general intellectual ability in offspring at high risk for psychoses and normal control subjects. Offspring of 182 parents with DSM-IV schizophrenia or affective psychoses 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 NCPP, and payment status, and on the offspring's age, sex, and history of obstetric complications. Based on data prospectively acquired from pregnancy and events of gestation, labor, delivery, and the neonatal period, we derived a measure of probable hypoxic-ischemic insult. We also report on standardized measures of general intelligence (intelligence quotient [IQ]) collected at age 7. General linear mixed models were used to test for the simultaneous effects of genetic vulnerability, defined as parental diagnosis, and probable hypoxic insult on age 7 IQ. Specificity of the effects for schizophrenia compared with affective psychoses and sex effects were also tested. Low IQ at age 7 was significantly associated with genetic vulnerability to psychoses, in particular with schizophrenia.