Scientists have discovered the link between gene expression, DNA methylation, and brain structural changes in depression, revealing new potential therapeutic targets.
By analysing gene interactions in mice subjected to behavioural tests, the researchers from Korea University Anam Hospital, Konkuk University, and Sahmyook University identified 141 genes primarily linked to immune responses correlating with depressive behaviours.
Parallel findings in humans underscored the involvement of interferon-related genes in major depressive disorder.
Scientists have long known that there may be a genetic component that confers predisposition to depression, but the specific underlying mechanisms have remained elusive. Growing evidence indicates that inflammation and immune-related processes in the brain could also play a significant role.
The study team employed a mouse model to measure immobility, a behaviour linked to depression, using a forced swim test. Through transcriptional profiling, they found that 141 genes significantly correlated with immobility, with 111 upregulated and 30 downregulated.
“We found that these genes were related to the interferon pathway, which is involved in the regulation of inflammation in the body,” explained Dr Se Jin Jeon from Sahmyook University.
Inflammation-related genes
The researchers further validated their findings through real-time PCR, confirming that immune-related genes were expressed at higher levels in mice with higher immobility scores.
To understand the findings in humans, 350 patients with major depressive disorder (MDD) and 161 healthy controls were examined. DNA methylation analysis – a technique used to study the epigenetic modifications on DNA – was conducted on the genes USP18 and IFI44, since these were found to be associated with depression-like behaviour in mice and were involved in interferon signalling pathways.
“In summary, we found elevated expression of inflammation-related genes in patients with depression compared to controls. This can increase inflammatory conditions in the body, including the brain, and ultimately lead to structural abnormalities in brain regions involved in emotional regulation, which may contribute to the development of depression,” concluded Dr Jeon.
