Matthew Girgenti, PhD, assistant professor of psychiatry, has been awarded a grant from the National Institute on Drug Abuse (NIDA) for a study about linking drug use to molecular changes in the brain that can lead to depression.
The award, a Director’s Pioneer grant under NIDA’s Avenir Award in Genetics and Epigenetics of Substance Use program, is for $1.5 million and the duration is for five years.
Title: “Functional convergence following disruption of diverse genes associated with cannabis use and major depression”
Abstract: There is strong association between cannabis use and depression and suicide, but the underlying cellular links are poorly understood. This presents a challenge for understanding how drug use can lead to additional psychiatric disorders. It is believed that cannabis use alters the development of key brain regions which in turn makes the brain more susceptible to additional stressors that could lead to major depressive disorder (MDD). These findings are particularly concerning given the popularity of cannabis legalization. According to Girgenti “One of the key unsolved problems is how to link drug use with specific molecular changes in the brain that can lead to depression. In this proposal, we take the first steps to bridging this gap.”
The proposed project addresses one of the major challenges in the genetics and epigenetics of drug addiction and how it can lead to additional psychiatric illness. Girgenti asks the question “does cannabis use cause depression?” and proposes tackling the chicken and egg problem of whether drug use leads to depression or vice versa (you are depressed and therefore use drugs). It is certainly possible (in fact likely) that it is a combination of these two phenomena but ultimately if you want to cure addiction you will need to find the relationship between drug use and other psychiatric disorders. This project will make a major contribution to the field by linking molecular levels across disorders, using an innovative combination of advanced single-cell type genomics in postmortem brain and regionally defined brain organoids.
Girgenti is a neuroscientist and molecular biologist in the Division of Molecular Psychiatry and the Wu Tsai Institute at Yale. He is also a VA-NCPTSD Research Scientist at the VA Connecticut Healthcare System in West Haven.