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A new study published in Psychological Medicine has found that individuals with major depressive disorder have brains that appear significantly older than their actual age, underscoring the connection between mental health and brain aging.
Recent scientific advances have begun to clarify how depression not only influences mood but also affects the brain’s physical structure. While aging is a natural process, growing evidence suggests that depression may accelerate some aspects of brain aging. However, much of this earlier research focused primarily on Western populations.
To address this gap, the new study analyzed brain scans from a Japanese cohort, aiming to determine whether the brains of individuals with major depressive disorder appear older than those of healthy individuals.
Led by Ruibin Zhang of Southern Medical University in China, the research team sought to investigate the biological factors underlying brain aging. They were particularly interested in how structural brain changes might be linked to alterations in key neurotransmitters and patterns of gene expression.
The study analyzed data from 670 participants, including 239 individuals with major depressive disorder and 431 healthy controls, collected from multiple sites in Japan. Using advanced brain imaging techniques, the researchers measured the thickness of various brain regions. They then applied a machine learning approach to analyze the images and calculate a “brain age” that reflected the extent of structural change.
The findings were striking. People with major depressive disorder had brains that appeared significantly older than those of their healthy peers. Specific areas of the brain—namely parts of the left ventral region and the premotor eye field—showed pronounced cortical thinning.
“These regions are primarily associated with higher-order cognitive functions, including attention, working memory, reasoning, and inhibition,” Zhang and colleagues explained.
The researchers also found that the areas with the greatest thinning were associated with changes in neurotransmitter systems—specifically, those involving dopamine, serotonin, and glutamate. These neurotransmitters play vital roles in mood regulation and cognitive processes, and their altered expression in individuals with depression suggests that biochemical disruptions may contribute to accelerated brain aging.
In addition, the team examined gene expression patterns and found that several genes involved in protein binding and processing were more active in the regions showing cortical thinning. These genes are essential for maintaining healthy cell structure and function. Disruptions in these pathways may lead to tissue degradation and contribute to faster brain aging in individuals with depression.
While the findings are compelling, the authors acknowledged several limitations. Most notably, the study was cross-sectional, meaning it captured data at a single point in time. Because brain aging is a gradual process, longitudinal studies are needed to understand how the frequency and severity of depression influence brain aging over time.
The study, “Accelerated brain aging in patients with major depressive disorder and its neurogenetic basis: evidence from neurotransmitters and gene expression profiles,” was authored by Haowei Dai, Lijing Niu, Lanxin Peng, Qian Li, Jiayuan Zhang, Keyin Chen, Xingqin Wang, Ruiwang Huang, Tatia M.C. Lee, and Ruibin Zhang.