Girgenti receives NIDA study scholarship

Matthew Girgenti, PhD, assistant professor of psychiatry, has received a grant from the National Institute on Drug Abuse (NIDA) to study the link between drug use and molecular changes in the brain that may lead to depression.

The award, a Director's Pioneer Grant under NIDA's Avenir Award in Genetics and Epigenetics of Substance Use program, is worth $1.5 million and will run for five years.

title: “Functional convergence after disruption of several genes associated with cannabis use and major depression”

Abstract: There is a strong link between cannabis use and depression and suicide, but the underlying cellular connections are not yet well understood. This poses a challenge for understanding how drug use may lead to further psychiatric disorders. Cannabis use is thought to alter the development of key brain regions, which in turn makes the brain more vulnerable to additional stressors that can lead to major depressive disorder (MDD). These findings are particularly concerning given the popularity of cannabis legalization. According to Girgenti, “one of the most important unsolved problems is how to link drug use to specific molecular changes in the brain that may lead to depression. In this proposal, we take the first steps to fill this gap.”

The proposed project addresses one of the biggest challenges in the genetics and epigenetics of drug addiction and how it can lead to further mental illness. Girgenti poses the question “Does cannabis use cause depression?” and proposes to address the chicken-and-egg problem of whether drug use leads to depression or vice versa (you are depressed and therefore take drugs). It is quite possible (and even likely) that it is a combination of these two phenomena, but if you want to cure addiction you ultimately need to figure out the relationship between drug use and other mental illnesses. This project will make a major contribution to the field by linking molecular levels across different disorders using an innovative combination of advanced single-cell genomics in the 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 investigator at the VA Connecticut Healthcare System in West Haven.