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I. Contributions of Genetic and Perinatal Factors

Tyrone D. Cannon, PhD; Sarnoff A. Mednicr, PhD, DrMed; Josef Parnas, MD; Fini Schulsinger, MD; Johannes Praestholm, MD; Aage Vestergaard, MD

Arch Gen Psychiatry. 1993;50(7):551-564.

Abstract
Objective
We examined the contributions of genetic risk for schizophrenia 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, one, or two parents, respectively, who were affected with schizophrenia spectrum disorders, evaluated initially in 1962 when they were on average 15 years old, and reexamined from 1986 through 1989 with psychiatric interviews and computed tomographic scans of the brain.

Results
After controlling for the effects of age, gender, substance abuse, and history of organic brain syndromes and head injuries, there were significant stepwise, linear increases in cortical and ventricular cerebrospinal fluidbrain ratios with increasing level of genetic risk for schizophrenia. Genetic risk for schizophrenia also interacted with prospectively assessed birth complications in predicting

selectively to enlargement of the ventricular system; ie, the effect of birth complications on ventricular enlargement was greater among those with two affected parents compared with those with one affected parent, and greater among those with one affected parent compared with those with normal parents. Perinatal exposure to ether anesthesia was associated with a generalized increase in brain abnormality, which varied in severity according to level of genetic risk for schizophrenia.

Conclusions
The type and degree of brain abnormalities shown by adult offspring of schizophrenic and normal parents are strongly predicted by the independent and interacting influences of genetic risk for schizophrenia and obstetric complications. The findings further substantiate the hypothesis that structural brain abnormalities in schizophrenia are at least in part neurodevelopmental in origin.

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