summary: New research reveals significant brain changes associated with suicide risk. Studies have identified excessive inflammation and loss of the brain’s protective mechanisms as key factors.
This breakthrough supports the possibility of using anti-inflammatory drugs to reduce suicide risk, especially during the early stages of suicidal ideation.
This study represents the most comprehensive analysis of gene methylation and transcriptomic data from the brains of suicide victims, providing new avenues for treatment and early risk detection.
Important facts:
- The study found increased inflammation and decreased activity of protective mechanisms in the brains of people who died by suicide.
- The main molecular changes identified include decreased activity of the NPAS4 gene, increased excitotoxicity, and decreased protective oligodendrocytes.
- The research could pave the way for blood tests to assess suicide risk and treatments that target inflammation.
sauce: Van Andel Institute
A first-of-its-kind study has identified excessive inflammation and the loss of key protective mechanisms in the brain as potential factors in suicide risk.
This finding supports further research into anti-inflammatory drugs to reduce risk, especially in settings where suicidal thoughts can be identified early.
The study was published in the journal molecular psychiatry It will be led by Lena Blandin, MD, of the Van Andel Institute, J. John Mann, MD, of Columbia University’s Department of Psychiatry, and Homer Stryker, MD, and Eric Acutis, MD, of Western Michigan University School of Medicine.
“As suicide rates continue to rise, we need to develop additional evidence-based strategies to address all the factors that contribute to suicide risk,” Brandin said. “Our research pinpoints some important changes in the brain that may one day be targeted by treatments, with the aim of reducing risks and saving lives.”
Suicidal behavior is caused by a combination of psychological, social, and biological factors. Previous research, including earlier findings by Brundin, Mann, and Achtyes, suggests that persistent inflammation can cause toxic imbalances, alter brain chemistry, and increase suicide risk.
The new findings build on this previous research by identifying key molecular differences that may cause inflammation and contribute to suicidal behavior.
The researchers compared the brains of 29 people who died by suicide with the brains of 32 people who died from other causes. Because most of the people who died by suicide in this study were not taking antidepressants or antipsychotics, the researchers were able to detect more molecular changes associated with suicide that might otherwise be hidden. I could see it clearly.
“Our goal is to prevent suicide by better understanding the brain functions associated with suicide,” Mann said.
“We focused on the brain because the biological processes that influence mood, suicidal thoughts and intentions, and decision-making reside in the brain. This study allows us to focus on the brain at moments of greatest risk. We were able to observe and pinpoint biological markers of that risk.”
Overall, the researchers found increased inflammation and decreased activity of mechanisms that protect the brain. Specific changes in the brain of people who die by suicide include the following:
- Gene activity decreases NPAS4, helps regulate inflammation and maintain brain cell health. This decreased activity causes inflammation.
- More excitotoxic, inflammatory processes that contribute to cell death.
- Oligodendrocytes, specialized cells that protect nerve fibers, decrease. There is evidence to suggest that these vital cells can weaken due to inflammatory damage, leaving nerve fibers vulnerable.
This study also represents the most thorough analysis to date of integrated gene methylation and transcriptomic data obtained from the brains of people who died by suicide.
Gene methylation is the process of turning genes “on” or “off” by annotating them with special chemical tags. The study found abnormal pro-inflammatory methylation patterns in people who died by suicide.
Alongside their current research, Blandin, Mann, Aktis and colleagues are looking for biomarkers, or measurable substances, in the blood that correspond to suicide risk. They envision a future where clinicians have validated blood tests to assess suicide risk and approve treatment strategies to reduce that risk, possibly by targeting inflammation.
Toward this goal, future research will focus on further understanding the role of inflammation in suicide risk, exploring biomarkers, and devising strategies to evaluate potential treatment options. It is.
“Clinicians desperately need enhanced methods to identify patients at increased risk of suicide,” Achtyes said. “Detecting patterns in molecular markers to alert those at increased risk could be a valuable tool to help those who are suffering.”
Note:Confidential matters 988 Lifeline for suicide and crisis is free and available 24/7 by dialing 988 or sending a text message.
Authors include Qiong Sha, Ph.D., Zhen Fu, Ph.D., Martha L. Escobar Galvis, Ph.D., Zach Madaj, M.A., and Jennifer A. Steiner, Ph.D., of VAI. Mark D. Underwood, MD, Andrew Dwork, MD, Norman Simpson, PhD, Hanga Galfalvy, PhD, and Gorazd Rozoklija, MD, of Columbia University; VAI’s Genomics Core and Bioinformatics and Biostatistics Core contributed to this research. The authors thank the families of the deceased participants for providing brain tissue and sharing clinical information.
Funding: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award No. 2. R01MH118211 (Brandin, Mann, Actis). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About this neuroinflammation and mental health research news
author: Beth Hinshaw
sauce: Van Andel Institute
contact: Beth Hinshaw – Van Andel Institute
image: Image credited to Neuroscience News
Original research: Open access.
“Integrated analysis of transcriptome and DNA methylation in brain tissue from the temporal pole of suicide decedents and their controls.Written by Lena Brandin et al. molecular psychiatry
abstract
IIntegrated transcriptome and DNA methylation analysis of brain tissue from the temporal pole of suicide decedents and their controls
Over the past two decades, suicide rates have steadily increased around the world, creating a serious public health crisis and placing an enormous burden on affected families and society as a whole. Suicidal behavior involves a multifactorial etiology, including psychological, social, and biological factors.
Because the molecular neural mechanisms of suicide remain largely unknown, we examined the transcriptional and methylation profiles of postmortem brain tissue from subjects who died by suicide and neurotypical healthy controls.
We performed RNA sequencing and DNA methylation profiling using an array targeting over 850,000 CpG sites in lateral polar tissue from 61 subjects who were naive to antidepressants and antipsychotics. It was analyzed using
expression of NPAS4An important regulator of inflammation and neuroprotection, it was significantly downregulated in the group of suicide deaths. Additionally, we identified a total of 40 differentially methylated regions that mapped to seven genes with inflammatory functions in the suicide death group.
There was an important relationship between NPAS4 DNA methylation and NPAS4 In the control group, expression that was not observed in the suicide death group was observed, confirming its dysregulation. NPAS4 The expression was significantly associated with the expression of multiple inflammatory factors in brain tissue.
Overall, gene sets and pathways closely related to inflammation were significantly upregulated, while specific pathways related to neuronal development were suppressed in the suicide death group.
Excitotoxicity and suppression of oligodendrocyte function were also implicated in suicide deaths. In summary, we have identified central nervous system inflammatory mechanisms that may be active during suicidal behavior, along with oligodendrocyte dysfunction and alterations in glutamatergic neurotransmission.
In these processes, NPAS4 may be a master regulator, and further studies are needed to examine its role as a potential biomarker or therapeutic target in suicidality.
