Groundbreaking study pinpoints brain-cell targets in depression
In a landmark effort to understand the biology of depression, researchers have for the first time pinpointed the exact brain cell types where gene activity and DNA regulation are disrupted. The team combined advanced genomic techniques with post-mortem brain tissue to identify the cells most affected by depression, offering a clearer picture of the condition’s biological roots.
Rare brain bank enables breakthrough
The study relied on tissue from the Douglas-Bell Canada Brain Bank, one of the few repositories worldwide that includes donations from individuals with psychiatric conditions. By examining thousands of individual brain cells, scientists could determine which cells behaved differently in people with depression and which DNA regulatory mechanisms might drive these differences.
Analyzing tissue from 59 individuals with depression and 41 without, the researchers used single-cell genomic techniques to map RNA and DNA activity. This allowed them to identify which cell types showed altered gene expression and chromatin accessibility, the latter revealing how DNA packaging influences gene activity.
Two cell types stand out as linked to depression
The most striking finding was that gene activity was altered in two distinct cellular populations: a class of excitatory neurons that regulate mood and responses to stress, and a subtype of microglia, the brain’s immune cells involved in inflammation. In both cell types, numerous genes were expressed differently in people with depression, suggesting disruptions in key neural circuits responsible for emotion regulation and brain resilience.
These results squarely position both neuronal and immune-related brain pathways at the center of depression biology, challenging older views that treated the condition as primarily a mood or behavioral issue without measurable brain-level changes.
What this means for understanding and treating depression
As senior author Dr. Gustavo Turecki of McGill University notes, the work provides a clearer map of where disruptions occur and which cells are involved. “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,” he said. “It gives us a much clearer picture of where disruptions are happening, and which cells are involved.”
By identifying the exact cellular players, the study deepens our understanding of the biological foundation of depression and helps debunk outdated notions of the condition as purely emotional. The researchers also intend to investigate how these cellular changes influence brain function and whether targeting these cells could yield more effective therapies in the future.
Looking ahead
Future work will explore how changes in excitatory neurons and microglia translate to altered neural circuits and behavior. If scientists can modulate the activity or inflammatory responses of these cells, it could open new avenues for treatments that address the underlying biology rather than just alleviating symptoms.
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. Authors include Anjali Chawla and Gustavo Turecki et al. Funding came from 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.
