Td. Cannon et al., DEVELOPMENTAL BRAIN ABNORMALITIES IN THE OFFSPRING OF SCHIZOPHRENIC MOTHERS .1. CONTRIBUTIONS OF GENETIC AND PERINATAL FACTORS, Archives of general psychiatry, 50(7), 1993, pp. 551-564
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.