This is a proposed Phase III of our Neurodevelopmental Study of Schizophrenia, in which we intend to assess the consequences of genetic and/or pre- and perinatal complications (PPCs) using high resolution structured magnetic resonance imaging (MRI). Studies of schizophrenia have implicated gray and white matter abnormalities in limbic-diencephalic, paralimbic, and prefrontal brain regions. These brain abnormalities result from genetic and/or environmental (i.e., obstetric) factors. Further, some nonpsychotic relatives of patients with schizophrenia suffer from similar, milder, (""""""""subsyndromal"""""""") dysfunctions. We are proposing a 5-year study to continue a 40-year prospective high risk study to directly test the consequences of genetic vulnerability (assessed by psychosis in the parent) and specific PPCs (i.e., chronic fetal hypoxia and infections in the second trimester), on cortical and subcortical brain volumes in adult offspring of parents with schizophrenia or affective psychoses. We have a unique opportunity to re-evaluate subjects that we have carefully studied by clinical and neuropsychological evaluations in Phase II of the study. The sample was originally ascertained from a community cohort of pregnancies drawn from the Providence and Boston cohorts of the National Collaborative Perinatal Project. At these sites, 17,741 pregnancies were followed prospectively and systematically recorded, and the offspring's mental and physical development were assessed at 4 and 8 months, and 1,4, and 7 years of age. We have systematically located, recruited, and diagnosed 200 parents with psychotic disorders, and 200 normal comparison parents, individually-matched on specific parent and offspring characteristics. 403 of their adult offspring, ages 31-37, have been identified in Phase II. We estimate that we will ascertain 85 percent of these 403 offspring for MRI. This study is unique in that we can specify developmental predictors of structural brain abnormalities and their functional consequences due to risk and obstetric status, for offspring who become psychotic, or exhibit subsyndromal expressions of the genetic diathesis. Further, we will identify the contribution of PPCs and/or genetic vulnerability to neural circuit abnormalities and demonstrate the specificity for schizophrenia versus affective psychosis. We will use a high resolution MRI and highly detailed, reliable image analysis techniques programs to link etiological predisposition to adult brain volumes (i.e., in limbic-diencephalic, paralimbic and cortical regions, and white matter tracts). This study has important implications for understand2ing the etiology and development of schizophrenia.
Showing the most recent 10 out of 14 publications
