Variation in the morphology of specific brain structures in schizophrenia may be attributable to genetic factors, environmental factors, or their interaction. Thus, neuroimaging studies of sibling pairs that vary in clinical, neuromorphological and genetic factors provide a powerful approach to evaluating brain structure abnormalities associated with the pathogenesis of schizophrenia. If specific genes underlie neurodevelopmental errors that are involved in the pathogenesis of schizophrenia, such genes could be discovered by examining the degree to which they segregate with brain structure abnormalities observed in schizophrenia subjects are the result of environmental factors or gene-environment interactions, controlling for such variability should facilitate efforts to detect other disease- related genes. Recently, we have developed tools for high dimensional brain mapping (HDBM) that permit the detailed analysis of brain structure volumes and shapes. We have used HDBM to compare the structure of the hippocampus in schizophrenia subjects and matched controls, and in these studies, shape deformities of the hippocampus were found to powerfully discriminate between groups. Thus, HDBM should be an ideal method for discovering neuromorphological abnormalities in non-psychotic siblings of schizophrenia, whom one would expect to show very subtle disturbances.
The specific aims of this Project are:
Aim 1. To collect high resolution magnetic resonance (MR) scans from sixty schizophrenia probands, their non-psychotic siblings sill within the age of risk for developing the disorder, and from matched controls;
Aim 2. To develop a database of neuromorphometric variables for each subject, including metrics for gray matter volume, thickness (for cortical surfaces), and shape, and for anisotropy;
Aim 3. To test the hypothesis that non-psychotic siblings of schizophrenia probands are discriminated from both schizophrenia subjects and healthy controls using neuromorphometric metrics. It is hypothesized that non-psychotic siblings will demonstrate brain structure abnormalities intermediate between the other two groups;
Aim 4. To examine relationships between gray and white matter metrics with related brain regions;
and Aim 5. To begin the collection of longitudinal data, with the ultimate goal of predicting the onset of schizophrenia in the non-psychotic siblings.
