Johns Hopkins School of Medicine

Neurobiological mechanisms of genetic risk for developmental brain disorders

Neurobiological mechanisms of genetic risk for developmental brain disorders Dr. Weinberger is director of the Lieber Institute for Brain Development, a multi-disciplinary translational neurobiology research institute focused on understanding the cellular and neural system mechanisms of genetic associations with schizophrenia and related developmental cognitive disorders. In the neuroscience of psychiatric disorders, two landmark developments have led to a sea change in our understanding and approach to these disorders. The first is the discovery of genes for risk and the second is the appreciation of the neurodevelopmental origins of these disorders. These historic developments have moved the field from characterization of the phenomenology of illness to identification of neurobiological mechanisms of illness. Dr. Weinberger heads a team of investigators studying genetic regulation of the transcriptome in normal human brain across the human life span from fetal life to advanced age, and in brains from patients with various psychiatric disorders and the impact of genetic variation on aspects of human brain development and function linked with risk for schizophrenia and related psychiatric disorders. He is working with unique clinical datasets and biological materials from a large sample of families (>1000) with affected and unaffected offspring and normal volunteers (>1000) collected while he directed the Genes, Cognition and Pychosis Program at the NIH. These datasets include DNA, lymphoblast and fibroblast cell lines, and extensive quantitative phenotypes related to genetic risk for schizophrenia, including detailed cognitive assessments and various neuroimaging assays. He is exploring at various levels of increasingly translational analysis the impact of genetic variation of interest on molecular processing of the gene, and on its implications for cognition and aspects of human temperament. He is also testing in multiple case control GWAS datasets maintained in the Lieber Institute for polygenic models of risk and for polygenic prediction of variation in relevant parameters of cognition and neuroimaging based phenotypes. The Lieber Institute also maintains two large clinical datasets related to antipsychotic drug response and these are also being interrogated for effects of putative susceptibility genes and genes related to drug metabolism.