Molecular Alterations in Brain Tissue Provide Clues to Suicidal Ideation

Summary: Researchers have identified molecular alterations in the blood and brain tissues of individuals who committed suicide, offering new insights into susceptibility factors and therapeutic targets.

The study analyzed genetic, protein, and metabolic changes, suggesting these alterations could serve as risk markers for suicidal behavior. By focusing on the neurobiological mechanisms behind suicide, the research aims to complement clinical interviews with molecular data to improve the identification and prevention of suicide risk.

This approach highlights the potential for novel pharmacological interventions and emphasizes the importance of understanding the biological underpinnings of suicidal actions to combat the stigma and provide timely intervention.

Key Facts:

  1. The study highlights molecular alterations in suicide victims, suggesting new pathways for understanding and preventing suicidal behavior.
  2. Researchers emphasized the role of the prefrontal cortex in behavioral control, noting its relevance in the context of young people’s susceptibility to suicide.
  3. Molecular findings include changes in neurotransmitters and transcription factors, pointing to potential targets for antidepressants and other treatments.

Source: FAPESP

In an article published in the journal Psychiatry Research, Brazilian scientists describe a number of molecular alterations found in the blood and brain tissue of individuals who committed suicide. According to the authors, the study aimed to identify susceptibility factors and potential targets for innovative pharmacological intervention.

More than 700,000 people take their own lives worldwide each year, according to the World Health Organization (WHO).

The suicide rate is particularly alarming in the 15-29 age group, where it is the fourth-ranking cause of death. This information is valid for 2019 and was taken from the latest edition of the WHO/IHME Global Burden of Disease (GBD), an epidemiological survey covering the main causes of death and disability in more than 200 countries.

This shows a brain.
The analysis also pointed to alterations to certain transcription factors (molecules responsible for regulating the expression of several genes). Credit: Neuroscience News

Several risk factors are associated with suicide, including family history, personality traits, socioeconomic conditions, exposure to toxic ideas on social media, and psychiatric disturbance, especially depression and bipolar disorder.

“However, despite the huge psychological, social and economic impact of deaths by suicide, identification of suicide risk is based on a clinical interview. The neurobiological mechanisms associated with suicidal behavior are poorly understood. They were the focus of our study,” said neuroscientist Manuella Kaster, a professor at the Federal University of Santa Catarina (UFSC) and co-principal investigator for the study alongside Daniel Martins-de-Souza, a professor at the State University of Campinas (UNICAMP).

According to Kaster, the group reviewed and reanalyzed a large amount of data available in the literature regarding molecular alterations found in postmortem examination of blood and brain tissue from suicides.

“Genes, proteins and metabolites in the samples were analyzed simultaneously and comparatively. We concluded that in complex conditions such as suicidal behavior, this kind of analysis has significant potential as a basis for identifying susceptibility factors and potential therapeutic targets,” Martins-de-Souza said.

Simply put, the molecular alterations can be interpreted as “risk markers” that point to novel pathways in neurobiology and offer strong support for the information acquired in clinical interviews.

“A noteworthy finding from several of the studies reviewed is that many subjects visit a health service in the year prior to a suicide or attempted suicide, but they do not receive the kind of care that could prevent such an outcome owing to the difficulty of identifying the risk,” Kaster said.

Caibe Alves Pereira, a PhD candidate at UFSC supervised by Kaster and first author of the article, analyzed data from 17 studies on alterations in brain gene and protein expression in suicides and similar data from subjects who died from other causes. The prefrontal cortex was the most frequently mentioned brain region in these sources.

“This brain region is connected to all the centers of emotional and impulse control. It plays a key role in behavioral flexibility and decision-making. Alterations to its structure or function can be highly relevant in the context of suicidal behavior,” Kaster said.

This relevance is especially significant in the case of young people since the prefrontal cortex is one of the last brain regions to mature. Alterations to cortical plasticity due to social, cultural, psychological or other factors can have a significant impact on emotional and behavioral control in the 15-29 age group.

When the data collected in the literature review was fed into an algorithm developed by Guilherme Reis-de-Oliveira, a PhD candidate at UNICAMP supervised by Martins-de-Souza and a co-author of the article, it was possible to identify biological mechanisms and pathways associated with suicide. Alterations to inhibitory neurotransmitters were among the main changes observed.

“Molecular alterations were associated above all with glial cells, such as astrocytes and microglia, which interact closely and dynamically with neurons and are fundamental to control of cellular communication, metabolism and plasticity,” Martins-de-Souza said.

The analysis also pointed to alterations to certain transcription factors (molecules responsible for regulating the expression of several genes).

“These included transcription factor CREB1, which has already been widely studied for its effects on neuroplasticity and as an important target for antidepressants. However, transcription factors MBNL1U2AF and ZEB2, which are associated with RNA splicing, formation of cortical connections and gliogenesis, have never been studied in the context of depression and suicide,” he said.

“Suicide must be taken seriously in all respects, from ideation to execution,” Kaster concluded.

“We know deaths by suicide are more prevalent among males, whereas attempted suicides are more prevalent among females, but this is due to the potential lethality and aggressiveness of the means utilized, as well as behavioral differences. Suicide is an avoidable cause of death if intervention is timely.

“This was the main motivation for our study. The stigma of suicide should be combated, so that a profound and broad understanding can be had of its various biological, social and cultural aspects, particularly the mechanisms involved in these behavioral alterations.”

About this genetics, neuroscience, and mental health research news

Author: Heloisa Reinert
Source: FAPESP
Contact: Heloisa Reinert – FAPESP
Image: The image is credited to Neuroscience News

Original Research: Open access.
Depicting the molecular features of suicidal behavior: a review from an “omics” perspective” by Manuella Kaster et al. Psychiatric Research


Depicting the molecular features of suicidal behavior: a review from an “omics” perspective


Suicide is one of the leading global causes of death. Behavior patterns from suicide ideation to completion are complex, involving multiple risk factors. Advances in technologies and large-scale bioinformatic tools are changing how we approach biomedical problems. The “omics” field may provide new knowledge about suicidal behavior to improve identification of relevant biological pathways associated with suicidal behavior.


We reviewed transcriptomic, proteomic, and metabolomic studies conducted in blood and post-mortem brains from individuals who experienced suicide or suicidal behavior. Omics data were combined using systems biology in silico, aiming at identifying major biological mechanisms and key molecules associated with suicide.


Post-mortem samples of suicide completers indicate major dysregulations in pathways associated with glial cells (astrocytes and microglia), neurotransmission (GABAergic and glutamatergic systems), neuroplasticity and cell survivor, immune responses and energy homeostasis. In the periphery, studies found alterations in molecules involved in immune responses, polyamines, lipid transport, energy homeostasis, and amino and nucleic acid metabolism.


We included only exploratory, non-hypothesis-driven studies; most studies only included one brain region and whole tissue analysis, and focused on suicide completers who were white males with almost none confounding factors.


We can highlight the importance of synaptic function, especially the balance between the inhibitory and excitatory synapses, and mechanisms associated with neuroplasticity, common pathways associated with psychiatric disorders. However, some of the pathways highlighted in this review, such as transcriptional factors associated with RNA splicing, formation of cortical connections, and gliogenesis, point to mechanisms that still need to be explored.

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