Understanding the Link Between Brain Inflammation and Suicide Risk

Breakthrough Study Reveals Groundbreaking Brain Changes Linked to Risk of Suicide

A revolutionary new study shows that individuals at risk of suicide display excessive inflammation and a decrease in protective brain mechanisms. The breakthrough paves the way for the potential utilization of anti-inflammatory medications to effectively mitigate suicide risk, particularly when identified during the early stages of suicidal thoughts.

This groundbreaking research, considered the most detailed analysis of gene methylation and transcriptomic data from the brains of suicide victims, introduces new treatment possibilities and an innovative approach to identifying early risk factors.

Key Facts:
The study identified increased brain inflammation and diminished activity in protective mechanisms in individuals who died by suicide.
Key molecular changes that were detected include a reduction in activity in the NPAS4 gene, increased excitotoxicty, and a decrease in protective oligodendrocytes.
The research culminates in the possible development of a blood test for assessing suicide risk and interventions targeting inflammation.

Source: Van Andel Research Institute

The first-of-its-kind study has established overactive inflammation and a loss of vital protective mechanisms in the brain as key contributing factors to suicide risk. The findings underscore the importance of further exploring the effectiveness of anti-inflammatory medications in reducing the risk of suicide, particularly in cases involving early detection of suicidal ideation. Future studies will focus on a deeper understanding of the role inflammation plays in suicide risk, the quest for biomarkers, and the development of strategies to evaluate potential treatment options.

The study was published in the journal Molecular Psychiatry, and was led by Lena Brundin, M.D., Ph.D., of Van Andel Research Institute, J. John Mann, M.D., of Columbia University Department of Psychiatry, and Eric Achtyes, M.D., M.S., of Western Michigan University Homer Stryker M.D. School of Medicine.

Lena Brundin expressed, “As suicide rates continue to rise, we must develop additional evidence-based strategies to address all the factors that contribute to suicide risk. Our study pinpoints several key changes in the brain that one day could be targeted for treatment with the goal of reducing risk and saving lives.”

The researchers highlighted that suicidal behavior is driven by a mix of psychological, social, and biological factors. Previous studies suggested that persistent inflammation may cause a toxic imbalance that alters brain chemistry and elevates suicide risk. The new findings build on this earlier work by identifying key molecular differences that drive inflammation and may contribute to suicidal behavior.

The research team compared the brains of 29 individuals who died by suicide to brains of 32 individuals who died from other causes. The participants who died by suicide were mostly not taking antidepressive and antipsychotic medications, which enabled the team to more clearly identify suicide-associated molecular changes that might otherwise be concealed.

J. John Mann stated, “Our goal is to prevent suicide by better understanding the brain function associated with it. We focused on the brain because that’s where the biological processes that affect mood, suicidal ideation and intent, and decision making reside. This study enabled us to see the brain at the moment of greatest risk and pinpoint biological markers of that risk.”

In overall findings, the team observed heightened inflammation coupled with a decrease in mechanisms that protect the brain. Specific changes in the brains of individuals who died by suicide include reduced activity in the gene NPAS4, which governs inflammation and aids in maintaining brain cell health. This decreased activity enables inflammation. Similarly, there was also an increase in excitoxicity, an inflammatory process linked to cell death, and a decrease in oligodendrocytes, which are specialized cells that protect nerve fibers. Evidence suggests that these vital cells may succumb to damage caused by inflammation, leaving nerve

fibers vulnerable.

The study also represents the most thorough analysis to date of integrated gene methylation and transcriptomic data derived from the brains of individuals who died by suicide. The study identified methylation patterns that promoted inflammatory-related aberrations.

In parallel with the current study, the researchers are also seeking blood-based biomarkers that correspond to suicide risk. The goal is a future where clinicians can effectively evaluate suicide risk and offer approved treatment strategies to mitigate that risk, potentially by targeting inflammation.

Eric Achtyes commented, “Clinicians desperately need enhanced ways to identify patients at increased risk of suicide. Detecting patterns in molecular markers to flag those at heightened risk could be a valuable tool for helping individuals who are struggling.”

Note: The confidential 988 Suicide & Crisis Lifeline is free and available 24/7 by dialing or texting 988.

Authors who contributed to the research include Qiong Sha, Ph.D., Zhen Fu, Ph.D., Martha L. Escobar Galvis, Ph.D., Zach Madaj, M.S., and Jennifer A. Steiner, Ph.D., of VAI; and Mark D. Underwood, Ph.D., Andrew Dwork, M.D., Norman Simpson, Hanga Galfalvy, Ph.D., and Gorazd Rozoklija, M.D., Ph.D., of Columbia University. VAI’s Genomics Core and Bioinformatics and Biostatistics Core contributed to this work. The authors thank the families of the deceased participants for their donation of brain tissue and sharing of clinical information.

Furthermore, the research work was supported by the National Institute of Mental Health of the National Institutes of Health under award no. R01MH118211. The contents are the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

About this neuroinflammation and mental health research news
Author: Beth Hinshaw
Source: Van Andel Research Institute
Contact: Beth Hinshaw – Van Andel Research Institute

Image: The image is credited to Neuroscience News

Original Research: Open-access study referenced in “Integrative transcriptome- and DNA methylation analysis of brain tissue from the temporal pole in suicide decedents and their controls” by Lena Brundin et al. Molecular Psychiatry


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