by A groundbreaking study has revealed that overactive inflammation and a loss of crucial protective mechanisms in the brain may contribute to an increased risk of suicide. This discovery could pave the way for the use of anti-inflammatory medications as a means of reducing suicide risk, particularly when early signs of suicidal thoughts are identified.
Despite an overall decline in suicide rates in the United States between 2019 and 2021, recent data from the Centers for Disease Control and Prevention (CDC) suggests that the number of suicides has once again risen. Similar patterns have been observed in the United Kingdom, while Australia has seen a steady increase in suicide deaths since 2013.
Suicidal behavior is influenced by a combination of psychological, social, and biological factors. Previous studies have suggested that inflammation may affect brain chemistry, elevating the risk of suicide. In an unprecedented study conducted at the Van Andel Institute in the United States, researchers investigated the biological mechanisms occurring in the brains of individuals who died by suicide to gain a deeper understanding of how they contribute to suicidal behavior.
“We aim to prevent suicide by gaining a better understanding of the brain’s function in relation to it,” said J John Mann, one of the co-authors of the study. “We focused on the brain because that’s where the biological processes that affect mood, suicidal thoughts, intent, and decision-making take place. This study allowed us to observe the brain at the moment of greatest risk and identify biological markers of that risk.”
The researchers compared postmortem brain tissue samples from 29 individuals who died by suicide with samples from 32 individuals who died suddenly from other causes such as accidents, homicides, or heart attacks (the control group). The samples were obtained from individuals aged 17 to 77. Toxicology screenings confirmed that the suicide decedents were largely not taking antidepressant or antipsychotic medications, which enabled the researchers to clearly identify suicide-related molecular changes that might have been obscured otherwise.
Through RNA sequencing and differential gene expression analysis of the samples, the researchers discovered that the NPAS4 gene, a key regulator of inflammation and brain cell health, was significantly downregulated in those who died by suicide. When examining gene methylation, the process that determines gene activation or suppression, the researchers found 40 differentially methylated regions in seven genes related to inflammation and immune response in suicide decedents. Importantly, there was a significant association between NPAS4 methylation and expression in the control group, which was absent in the suicide decedent group, confirming dysregulation.
Overall, the suicide decedent group exhibited an activation of gene sets associated with inflammation and excitotoxic mechanisms. Excitotoxicity occurs when nerve cells are damaged or die due to abnormally high levels of neurotransmitters. The balance between inhibitory and excitatory neurotransmitters plays a crucial role in various psychiatric disorders, including major depressive disorder.
In addition to the overactive inflammatory mechanisms, there was also a suppression of gene sets related to the maturation of oligodendrocytes, specialized cells that protect neurons by wrapping them in myelin and safeguarding against oxidative damage. The researchers observed a decreased number of oligodendrocytes.
The researchers suggest that their study provides support for further investigation into the use of anti-inflammatory medications for reducing the risk of suicidal behavior, particularly in cases where suicidal thoughts have been identified.
“As suicide rates continue to rise, we must develop evidence-based strategies to address all the factors contributing to suicide risk,” said Lena Brundin, corresponding author of the study. “Our research identifies several key changes in the brain that could be targeted for treatment in order to reduce risk and save lives.”
The study’s findings also hold promise for researchers who are seeking blood biomarkers that correspond to suicide risk. Future studies will further explore the role of inflammation in suicide risk, identify biomarkers, and develop strategies to evaluate potential treatment options.
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- Source: Coherent Market Insights, Public sources, Desk research
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