Sarnoff A. Mednick - The High Risk For Schizophrenia Study

The High Risk For Schizophrenia Study

At the time the High-Risk-for-Schizophrenia study began, in 1962, the offspring of the women with schizophrenia were average age 15 and had not come into the risk period for schizophrenia. By the early eighties, many of the study's subjects had fallen ill with schizophrenia. Colleagues and students of Mednick began to examine the association between schizophrenia outcomes and earlier risk factors. Interestingly, perhaps the first study to support Kraepelin's notion of dementia praecox (that persons with schizophrenia had early dementia), was a study that showed that offspring of those with schizophrenia who had the most serious symptomatology had enlarged ventricles on CT scans suggestive of brain atrophy. In a study by Silverton et al. those with the most severe schizophrenia symptoms on outcome had low birthweights decades before. Their hypothesis that low birthweight might be associated with insults in utero was corroborated. In a follow-up study, the authors tested the notion that schizophrenia is the result of a genetic by environmental interaction, that is that insults in utero may be specifically stressful to persons with a brain vulnerability to schizophrenia. In a follow-up study, Leigh Silverton and Sarnoff Mednick at the University of Southern California hypothesized an interaction between genetic risk for schizophrenia might be most vulnerable to insults in utero. This would be considered a gene X environment interaction, a model for the pathogenesis of schizophrenia that Silverton and Mednick began working on in the early eighties. The authors conducted another study in which they separated subjects into high-risk and "super-high risk" and measured the interaction between genetic risk and birthweight in its effect on Ventricle-to-Brain ratio. They found that those most vulnerable to low birthweight, a variable representing subtle birth difficulties in utero, were most likely to have early cerebral ventricular enlargement on CT-scans. At the time, the idea both that schizophrenia was a brain disease and that it could represent a gene x environment interaction was novel. This was possibly the first study to support the notion that earlier findings of brain abnormalities in schizophrenia were not only etiologically significant but related to early environmental factors (such as pregnancy and birth complications or in utero insults), and that pathogenesis was related to factors that could be prevented. Other factors associated with breaking down with schizophrenia were shown by Elaine Walker and Robert Cudeck along with Mednick to be separation for parents (even mothers with schizophrenia) if it lead to institutionalization. Interestingly, the outcome of the High-Risk-for-Schizophrenia study showed that it was the interaction between genetics and environment that accounted for schizophrenia. It also suggested that the final common pathway to schizophrenia is expressed as a brain disease.

Before the High Risk for Schizophrenia study, a theory that poverty caused schizophrenia developed because persons with schizophrenia were found in the most impoverished regions of the city. Silverton and Mednick hypothesized, on the other hand that those with schizophrenia drifted into the lower classes as their disease caused a cognitive disability and therefore difficulty working. In a 1984 study, they found that high risk subjects matched for socioeconomic status at birth drifted into lower social classes as the result (rather than the cause) of schizophrenia

In a 2008 study (supported by a grant to Silverton from the American Foundation for Suicide Prevention) of the High Risk for Schizophrenia subjects, Silverton, Mednick, Holst and John showed that although those with schizophrenia may drift into lower social class regions, those of higher social class origins who develop schizophrenia suicide at a higher rate than those from lower social classes. The authors reasoned the although schizophrenia may largely be a brain disease, the response to cognitive impairments caused by the disorder, may be harder for those from a higher initial social classes and therefore higher self-expectations.