In an article published in the magazine Psychiatry Research, Brazilian researchers describe a set of molecular changes present in the brain and blood of individuals who committed suicide. According to the authors, the objective was to identify susceptibility factors and potential therapeutic targets.
According to the World Health Organization (WHO), more than 700,000 people die by suicide every year around the world. Among young people, a term that refers to the age group from 15 to 29 years old, the impact of suicide is particularly alarming, representing the fourth leading cause of death. The data, from 2019, were obtained in the latest edition of the Global Burden of Disease (GBD), an epidemiological study that brings together more than 200 countries and provides a comprehensive picture of the main causes of mortality and global disability.
Several risk factors are associated with suicide, including family history, personality traits, socioeconomic conditions, exposure to harmful ideas on social media and the presence of psychiatric disorders, especially depression and bipolar disorder. “However, despite the enormous psychological, social and economic impact generated by suicide deaths, risk identification is only based on clinical interviews. The neurobiological mechanisms associated with behavioral changes are still poorly understood. And that was the focus of our study”, says the neuroscientist Manuella Kaster professor at the Federal University of Santa Catarina (UFSC) and research coordinator alongside Daniel Martins-de-Souza 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 on molecular changes found in the brain and blood of individuals who committed suicide. “The use of tools such as transcriptomics, proteomics and metabolomics allowed the simultaneous and comparative evaluation of genes, proteins and metabolites present in samples. And we found that, in complex conditions such as suicide, these analyzes have great potential, as they can provide the basis for identifying susceptibility factors, in addition to potential therapeutic targets”, adds Martins-de-Souza.
Simply put, molecular changes can be interpreted as “risk markers” and provide new clues in neurobiology, constituting an important aid to the information collected in clinical interviews. “A notable finding observed in different studies is that many individuals seek health services in the year before attempting suicide or committing suicide. But, due to the difficulties in identifying the risk, they do not receive the attention that could avoid the outcome”, says Kaster.
Caibe Alves Pereira, PhD student at UFSC supervised by Kaster and first author of the article, collected 17 studies that provided information on brain changes in the expression of genes and proteins in individuals who committed suicide, in comparison with data from individuals affected by other causes of death. The prefrontal cortex was the brain region most evaluated.
“This region of the brain has a great connection with the emotional control and impulse control centers. It is fundamental in behavioral flexibility and decision-making processes. Changes in its structure or function can be extremely relevant in the context of suicidal behavior”, highlights Kaster.
Such information is especially relevant in the case of young people, because the prefrontal cortex is one of the last regions of the brain to mature. Changes in plasticity mechanisms in the prefrontal cortex, affected by different risk factors (social, cultural, psychological, etc.), can have a significant impact on emotional and behavioral control in young individuals.
In the study in question, data from different works were combined. And, through an algorithm developed by Guilherme Reis de Oliveira, a doctoral student at Unicamp supervised by Martins-de-Souza and participant in the article, it was possible to identify some biological mechanisms and common pathways associated with suicide. Changes in neurotransmitter systems, especially inhibitory neurotransmitters, appeared as the main changes observed. “The molecular changes were mainly associated with glial cells, such as astrocytes and microglia, which have a close and dynamic interaction with neurons and are fundamental in controlling cellular communication, metabolism and plasticity”, says Martins-de-Souza.
According to the researcher, data analysis also pointed to changes in some transcription factors: molecules responsible for regulating the expression of several genes. “Among them, the transcription factor CREB1 It has already been widely explored for its effects on neuroplasticity and for being an important target in the effect of antidepressant drugs. However, transcription factors MBNL1, U2AF It is ZEB2 associated with the processing of RNA molecules, formation of cortical connections and gliogenesis, have never been studied in the context of depression and suicide”, he details.
And Kaster concludes: “From ideation to execution, suicide must be taken seriously. We know that suicide deaths are more prevalent in males, while suicide attempts are more prevalent in females. But this is due to the potential for lethality and aggressiveness of the means used and differences in behavioral aspects. Suicide is a preventable cause of death with timely interventions. And this is the main motivation of our study. It is necessary to reduce stigma and understand, in a broad and deep way, the different biological, social and cultural aspects involved in behavioral changes”.
The investigation received support from FAPESP through three projects (17/25588-1, 18/01410-1 It is 19/25957-2).