Researchers at McGill University and the Douglas Institute have pinpointed two types of brain cells altered in people with depression. Using advanced genomic analysis on post-mortem brain tissue, they found genetic disruptions in excitatory neurons and microglia. The findings, published in Nature Genetics, could lead to more targeted treatments for the condition affecting over 264 million people worldwide.
The study, published on October 10, 2025, in Nature Genetics, represents a breakthrough in understanding the biological basis of depression. Scientists analyzed RNA and DNA from thousands of individual brain cells sourced from the Douglas-Bell Canada Brain Bank, a rare collection of post-mortem tissue from individuals with psychiatric conditions. The research examined samples from 59 people who had depression and 41 who did not, revealing significant differences in gene activity.
Two key cell types showed alterations: a class of excitatory neurons involved in mood and stress regulation, and a subtype of microglia, the brain's immune cells that control inflammation. In both, many genes were expressed differently in those with depression, indicating disruptions in neural and inflammatory systems.
"This is the first time we've been able to identify what specific brain cell types are affected in depression by mapping gene activity together with mechanisms that regulate the DNA code," said senior author Dr. Gustavo Turecki, a professor at McGill University, clinician-scientist at the Douglas Institute, and Canada Research Chair in Major Depressive Disorder and Suicide. He added, "It gives us a much clearer picture of where disruptions are happening, and which cells are involved."
The work, titled "Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression," was led by Anjali Chawla and Gustavo Turecki, with contributions from researchers including Doruk Cakmakci and Laura M. Fiori. Funded by the Canadian Institutes of Health Research, Brain Canada Foundation, and others, it underscores depression's measurable brain changes.
"This research reinforces what neuroscience has been telling us for years," Turecki noted. "Depression isn't just emotional, it reflects real, measurable changes in the brain."
Looking forward, the team plans to investigate how these cellular changes affect brain function and explore targeted therapies, potentially improving outcomes for one of the world's leading causes of disability.