Depression is a common mental health problem that affects people of all shapes and sizes; scientists have known for some time that there may be a genetic component that confers susceptibility to depression, but they have not yet elucidated the mechanisms behind it, and now a growing body of evidence suggests that inflammatory and immune-related processes in the brain may play an important role in the development of depression. Recently, a study entitled "Correlation between immune-related genes and depression-like features in an animal model and in humans" was published in the international journal Brain, Behavior, and Immunity. Correlation between immune-related genes and depression-like features in an animal model and in humans" in the international journal Brain, Behavior, and Immunity, scientists from Sanyuk University and other institutions in South Korea have unraveled the molecular pathways behind the development of depression.
In the article, the researchers used a mouse model to measure immobility, a behavior associated with depression, through the forced swim test; through transcriptome profiling, they found 141 genes significantly associated with immobility, of which 111 genes were up-regulated and 30 genes were down-regulated. up-regulated and 30 down-regulated. Dr. Jeon explained that these genes were associated with the interference pathway, which is mainly involved in the regulation of inflammation in the body. The researchers then verified their findings by real-time PCR and confirmed that immune-related genes may be expressed at a high level in mice with high immobility scores.
In addition, the researchers used intracerebroventricular injections to induce an immune response in the mice, which led to an increase in immobility and activation of microglia, which may provide further evidence for accepting the association between immune response genes and indicators of depression. Using the results of the mouse study, the researchers aimed to understand the association between DNA methylation, structural changes in the brain, and depression in the human organism, and to do so they analyzed 350 patients with major depressive disorder (MDD, major depressive disorder) and 161 healthy controls; DNA methylation analysis is a technique used to study epigenetic modifications on DNA, and the researchers used this technique to examine the relationship between DNA methylation and depression. DNA methylation analysis is a technique used to study epigenetic modifications on DNA, and the researchers used it to correlate the USP18 and IFI44 genes, as these genes are associated with depression-like behaviors in the mouse organism and are mainly involved in the interferon signaling pathway.
The researchers found differences in methylation patterns in the organism between patients with major depression and healthy controls; in patients with major depression, DNA methylation in a specific region of the USP18 gene was associated with reduced thickness in multiple mood- and cognition-related brain regions; meanwhile, in healthy controls, DNA methylation in another region of the USP18 gene was associated with increased thickness of brain regions in which vision and sensation are related brain regions; these findings link not only the expression of immune-related genes, but also their epigenetic status to their effects on brain structure and depression.
Overall, we found that the expression levels of inflammation-related genes were elevated in the bodies of depressed patients compared to controls, which may increase the inflammatory state of the body (including the brain) and ultimately lead to structural abnormalities in brain regions involved in mood regulation, leading to depression; therefore, these immune genes may hold promise as a viable therapeutic target to provide an alternative approach or supplement to currently approved pharmacotherapeutic treatments.
In summary, the researchers' analysis of transcriptomic data and animal behavior in this study may enhance scientists' understanding of the pathogenesis of human depression and provide new ideas and hope for the development of novel depression therapies.
