DEVELOPMENTAL BRAIN ABNORMALITIES IN THE OFFSPRING OF SCHIZOPHRENIC MOTHERS .1. CONTRIBUTIONS OF GENETIC AND PERINATAL FACTORS

Objective: We examined the contributions of genetic risk for schizophr enia and obstetric complications to brain morphological abnormalities in the offspring of schizophrenic and normal patents. Methods: We used a cohort analytic study of 60, 72, and 25 individuals with neither, o ne, or two parents, respectively, who were affected with schizophrenia spectrum disorders, evaluated initially in 1962 when they were on ave rage 15 years old, and reexamined from 1986 through 1989 with psychiat ric interviews and computed tomographic scans of the brain. Results: A fter controlling for the effects of age, gender, substance abuse, and history of organic brain syndromes and head injuries, there were signi ficant stepwise, linear increases in cortical and ventricular cerebros pinal fluid-brain ratios with increasing level of genetic risk for sch izophrenia. Genetic risk for schizophrenia also interacted with prospe ctively assessed birth complications in predicting selectively to enla rgement of the ventricular system; ie, the effect of birth complicatio ns on ventricular enlargement was greater among those with two affecte d parents compared with those with one affected parent, and greater am ong those with one affected parent compared with those with normal par ents. Perinatal exposure to ether anesthesia was associated with a gen eralized increase in brain abnormality, which varied in severity accor ding to level of genetic risk for schizophrenia. Conclusions: The type and degree of brain abnormalities shown by adult offspring of schizop hrenic and normal parents are strongly predicted by the independent an d interacting influences of genetic risk for schizophrenia and obstetr ic complications. The findings further substantiate the hypothesis tha t structural brain abnormalities in schizophrenia are at least in part neurodevelopmental in origin.