The Program for Neuropsychiatric Research (PNPR) at McLean Hospital, with collaborating sites in other locations, is a consortium of investigators and clinicians using laboratory, brain imaging, and clinical techniques to increase understanding of the causes of the most common and devastating brain disorders, psychotic, mood, and neurodegenerative conditions, including schizophrenias, bipolar disorders, major depressions, and Alzheimer’s disease.  That knowledge can guide the development of improved treatments.

Clinical phenotyping of participants includes standardized diagnostic schedules and symptom scales. DNA is obtained for genetic studies on all subjects. Many subjects undergo structural, spectroscopic, and functional brain imaging. Similarly, biopsies are obtained from many subjects and skin cells (fibroblasts) are isolated from these specimens, dedifferentiated to iPS lines, and reprogrammed and studied as brain cells and neural and glial lines, in culture.  A hallmark of the research is combining results from all of the modalities of study to find convergent evidence on the biological pathways underlying neuropsychiatric disorders.

Findings from our group include abnormalities of bioenergetics and mitochondrial function in psychotic, mood, and neurodegenerative disorders and abnormalities of connectivity and myelination, especially in those with schizophrenia.  Combined evidence from genomics, cell biology, and imaging consistently suggest that these mechanisms explain substantial portions of the risk for psychiatric disorders. The findings and the cell lines may be of great use in the identification of new targets and the testing of novel interventions for the treatment of neuropsychiatric disorders.