The role of genetics and epigenetic changes in depression

Sahmyook University researchers discover molecular mechanisms under stress

The role of genetics and epigenetic changes in depression

image: Using both mice and human models, researchers investigated the link between gene expression, DNA methylation, and brain structural changes in depression. Their findings highlight the involvement of interferon-related genes in major depressive disorders.
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Credit: Se Jin Jeon from Sahmyook University

Depression is a common mental health problem that affects people everywhere. Scientists have long known that there may be a genetic component that predisposes to depression, but the underlying mechanisms have not been identified. A growing body of evidence suggests that inflammation and related physiological processes in the brain may play an important role in depression.

A team of researchers including Dr. Se Jin Jeon from Sahmyook University conducted research to gain in-depth knowledge of these methods. Their study was made available online on June 26, 2023 and published in October 2023 in Volume 113 of the journal. Brain, Behavior, and Immunity.

The team employed a mouse model to measure their immobility, a behavior associated with depression, using the forced swim test. Using transcriptional profiling, they found that 141 genes are highly correlated with the absence, with 111 upregulated and 30 downregulated. “We discovered that these genes are related to the interferon pathway, which is involved in controlling inflammation in the body.”, explains Dr. Jeon. The researchers further confirmed their results with real-time PCR, confirming that genes related to the body were expressed at higher levels in mice with high immobility scores. In addition, they induced immune responses using an intracerebroventricular injection, which led to an increase in immobility and microglial activity, providing additional evidence about the link between immune response genes and depression indicators.

Using the results of murine research, the group aims to understand the link between DNA methylation, changes in brain structure, and depression in humans. For this, 350 patients with major depressive disorder (MDD) and 161 healthy controls were examined. DNA methylation analysis—a technique used to study epigenetic changes in DNA—is performed on genes. USP18 and FI44, since these have been found to be associated with depressed behavior in mice and are involved in interferon signaling pathways. The researchers found differences in methylation patterns between patients with MDD and controls. In patients with MDD, DNA methylation of a specific region in the USP18 a gene associated with reduced size in several areas of the brain related to emotion and cognition. Meanwhile, in the control group, DNA methylation of another region in the USP18 associated with increased thickness in brain regions associated with vision and emotional processing. These results combine not only the expression of genes related to the body, but also their epigenetic status and their effect on brain structure, and depression.

In summary, we found elevated expression of inflammation-related genes in patients with depression compared to controls. This can increase inflammation in the body, including the brain, and ultimately lead to structural abnormalities in brain regions involved in emotional regulation, which can contribute to the development of depression.”, concludes Dr. Jeon.

Thus, by being able to serve as effective therapeutic targets, these immune genes provide an alternative or supplement to currently approved pharmacologic treatments.




About the center

Sahmyook University is located in the metropolis of Seoul, South Korea. The university is famous for its clean campus, earning the title of “the most beautiful university in Korea.” Its commitment to environmental sustainability is reflected in its eco-friendly construction. The university prides itself on its unique academic advising program where students and professors work together to find and provide guidance. Consisting of six colleges, including the College of Theology, Humanities & Social Sciences, and Health Sciences and Social Welfare, as well as four graduate schools, Sahmyook University offers a comprehensive educational experience.


About the author

Dr. Se Jin Jeon received his Pharmacology from Seoul National University and completed his medical training at the University of California, Los Angeles, USA. Currently, he teaches pharmacology and new drug development as an assistant professor in the Department of Bio Convergence Engineering at Sahmyook University.

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