Groundbreaking discovery maps which brain cells are affected in depression
In a landmark study, researchers have for the first time pinpointed the specific brain cell types that show altered activity in depression. By combining gene activity data with mechanisms that regulate the DNA code, the team has created a clearer map of where disruptions occur and which cells are involved. The finding moves beyond broad explanations of depression as purely emotional, showing measurable cellular changes in the brain.
Senior author Dr. Gustavo Turecki of McGill University emphasized the significance: “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. It gives us a much clearer picture of where disruptions are happening, and which cells are involved.”
How the study was conducted
The team used post-mortem brain tissue from the Douglas-Bell Canada Brain Bank, one of the few collections worldwide with donations from people who have psychiatric conditions. Through advanced single-cell genomic analysis, 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.
By combining these data, scientists could identify cells that stood apart in depression and then link those differences to specific genetic regulatory mechanisms. This dual approach allowed the researchers to move beyond general associations and toward a cell-type–level understanding of the disorder.
Two key cell types implicated in depression
The analysis revealed altered gene activity in two distinct brain cell categories. The first is a class of excitatory neurons that play a central role in mood regulation and responses to stress. The second is a subtype of microglia, the brain’s immune cells that manage inflammation and other responses. In both cell types, many genes were expressed differently in people with depression, suggesting disruptions to fundamental neural circuits underlying mood and cognition.
“Depression isn’t just emotional; it reflects real, measurable changes in the brain,” said Dr. Turecki. The identification of these two cell types provides a concrete biological basis for understanding how depression alters neural function at the cellular level.
Implications for treatment and future research
While the findings mark a major conceptual advance, the researchers stress that more work is needed to translate these cellular changes into therapies. The team plans to investigate how the identified cellular alterations influence brain function and whether strategies to target these cells or their regulatory pathways could yield more effective treatments for depression.
As neuroscience progresses, this study helps dispel outdated notions that depression is purely a psychological phenomenon. The data reinforce the view that mental health disorders involve real, measurable brain biology that can be studied and potentially modified with targeted interventions.
About the study
The study, titled “Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression,” was published in Nature Genetics by Anjali Chawla, Gustavo Turecki, and colleagues. It was funded by the Canadian Institutes of Health Research, Brain Canada Foundation, Fonds de recherche du Québec – Santé, and the Healthy Brains, Healthy Lives initiative at McGill University.
