Translating findings from clinical genetics to postmortem human brain tissue will lead to the identification of targets for novel therapeutic agents to treat schizophrenia and other complex neuropsychiatric disorders.
Clinical and Pathological Mechanisms of Genetic Risk
Large clinical studies are revealing genetic traits that increase the risk for schizophrenia and other developmental disorders of the brain. In order to understand how a particular genetic variant changes brain chemistry and/or anatomy, postmortem human brain tissue must be studied. Applying the findings from postmortem human brain, scientists can develop more faithful and useful animal and cell models, which will accelerate the pace of drug development. Advancing the mission of the Lieber Institute, the Molecular Neuropathology Section has established one of the world’s largest and most carefully curated postmortem human brain repositories (over 2200 thus far) dedicated to neuropsychiatric and neurodegenerative research. In addition to schizophrenia, areas of focus include bipolar disorder, PTSD, major depressive disorder, autism, Alzheimer’s disease, Parkinson’s disease, Lewy body disease, and more.
Importantly, the Lieber Institute also has one of the largest normal “control” human brain collections in the world. Control subjects, free of neurological or psychiatric disorder, reveal how the brain develops, and the subtle effects of genetic variation on aspects of that development. The Molecular Neuropathology group pairs highly detailed clinical and demographic classifications on the 2200+ human brain donors with extensive tissue, blood, patient dura derived cell line, RNA, and DNA samples. We also have multiple levels of information related to quality control on every case in the repository, including but not limited to postmortem interval, RNA integrity number, pH, and toxicology testing for illicit substances and therapeutic medications.
The Molecular Neuropathology Team works closely with the other research teams at the Lieber Institute, exploring the bases of polygenic psychiatric and neurodegenerative disorders in the human brain.