Researchers found that certain neurons and microglia function differently in depressed individuals, altering brain systems tied to emotion and stress. The discovery could lead to precision therapies that target the root cellular mechanisms of depression.

Two key brain cell types show genetic disruptions in depression—offering hope for more effective, targeted treatments.

Source:

McGill University

Summary:

Scientists identified two types of brain cells, neurons and microglia, that are altered in people with depression. Through genomic mapping of post-mortem brain tissue, they found major differences in gene activity affecting mood and inflammation. The findings reinforce that depression has a clear biological foundation and open new doors for treatment development.

FULL STORY

Scientists at McGill University and the Douglas Institute have discovered that two distinct types of brain cells show changes in people experiencing depression.

Published in Nature Genetics, the research provides new clues that could guide the creation of treatments focused on these specific cells. It also enhances scientific understanding of depression, a condition that affects more than 264 million people globally and is one of the leading causes of disability.

"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, clinician-scientist at the Douglas Institute and Canada Research Chair in Major Depressive Disorder and Suicide. "It gives us a much clearer picture of where disruptions are happening, and which cells are involved."

Rare brain bank enables breakthrough

The team conducted their work using post-mortem brain tissue from the Douglas-Bell Canada Brain Bank, one of the few collections worldwide that includes donations from people with psychiatric conditions.

Through advanced single-cell genomic analysis, the researchers examined RNA and DNA from thousands of individual brain cells to determine which ones behaved differently in people with depression and which DNA sequences might explain these variations. The study analyzed tissue from 59 individuals who had depression and 41 who did not.

They discovered that gene activity was altered in two types of brain cells: a class of excitatory neurons responsible for mood and stress regulation, and a subtype of microglia, the immune cells that manage inflammation in the brain. In both cell types, many genes were expressed differently in people with depression, pointing to possible disruptions in vital neural systems.

By identifying the specific cells affected, the research deepens understanding of the biological foundation of depression and helps dispel outdated views of the condition.

"This research reinforces what neuroscience has been telling us for years," Turecki said. "Depression isn't just emotional, it reflects real, measurable changes in the brain."

Looking ahead, the scientists intend to explore how these cellular changes influence brain function and whether targeting them could lead to more effective treatments.

About the study

"Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression" by Anjali Chawla and Gustavo Turecki et al., was published in Nature Genetics.

The study was funded by Canadian Institutes of Health Research, Brain Canada Foundation, Fonds de recherche du Québec - Santé and Healthy Brains, Healthy Lives initiative at McGill University.

Journal Reference:

1. Anjali Chawla, Doruk Cakmakci, Laura M. Fiori, Wenmin Zang, Malosree Maitra, Jennie Yang, Dariusz Żurawek, Gabriella Frosi, Reza Rahimian, Haruka Mitsuhashi, Maria Antonietta Davoli, Ryan Denniston, Gary Gang Chen, Volodymyr Yerko, Deborah Mash, Kiran Girdhar, Schahram Akbarian, Naguib Mechawar, Matthew Suderman, Yue Li, Corina Nagy, Gustavo Turecki. Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression. Nature Genetics, 2025; 57 (8): 1890 DOI: 10.1038/s41588-025-02249-4