Project Summary

Amy F. T. Arnsten, Ph.D. (Distinguished Investigator 2008) of Yale University School of Medicine, is applying new methods of genetic manipulation to help explain why loss of function in the DISC1 (Disrupted in schizophrenia 1) gene contributes to symptoms of mental illness and particularly to the course of illness in schizophrenia. Among the questions being asked in this research is whether loss of DISC1 function in the prefrontal cortex (PFC) region of the brain leads to PFC network collapse, cognitive dysfunction and loss of dendritic spines, which are the protrusions on nerve cells that receive messages during the process of neurotransmission. Another question that will be explored is why some molecules unrecognized until recently can exert powerful effects on cortical circuits that malfunction in mental illness, data that will complement studies of the role of DISC1 in the developing PFC. This work will also expand genetic tools for research. It will be the first use in monkey studies of short hairpin RNA (shRNA). This is a sequence of RNA so named because it makes a tight hairpin turn that can be used to silence gene expression. This technology can be applied to study many genes of involved in higher cognitive function, and for examining how genetic alterations manifest as symptoms of mental illness.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS

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