Certain molecular changes in the brain and blood have been found to be associated with those who died by suicide. — Gordon Johnson/Pixabay
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.
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 behaviour are poorly understood.
“They were the focus of our study,” said co-principal investigator and Brazil’s Federal University of Santa Catarina (UFSC) neuroscientist Professor Dr Manuella Kaster.
According to her, the group reviewed and reanalysed a large amount of data available in the scientific literature regarding molecular alterations found in postmortem (after death) examination of blood and brain tissue from people who died by suicide.
Taken from 17 studies, the data on alterations in brain gene and protein expression in both people who died by suicide and those who died from other causes was reviewed and analysed by study first author and UFSC PhD candidate Caibe Alves Pereira via an algorithm developed by co-author and Brazil’s State University of Campinas (Unicamp) PhD candidate Guilherme Reis-de-Oliveira.
Alterations to inhibitory neurotransmitters were among the main changes observed in the biological mechanisms and pathways associated with suicide.
“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,” said study co-principal investigator and Unicamp molecular biologist Associate Prof Dr Daniel Martins-de-Souza.
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 MBNL1, U2AF and ZEB2, which are associated with RNA [ribonucleic acid] splicing, formation of cortical connections and gliogenesis, have never been studied in the context of depression and suicide,” he said.
“We concluded that in complex conditions such as suicidal behaviour, this kind of analysis has significant potential as a basis for identifying susceptibility factors and potential therapeutic targets,” he added.
Simply put, the molecular alterations can be interpreted as “risk markers” that point to new pathways in neurobiology and offer strong support for the information acquired in clinical interviews.
The prefrontal cortex was the most frequently mentioned brain region in the original studies.
“This brain region is connected to all the centres of emotional and impulse control.
“It plays a key role in behavioural flexibility and decision-making.
“Alterations to its structure or function can be highly relevant in the context of suicidal behaviour,” Prof Kaster said.
This is especially significant in the case of young people as 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 behavioural control in the 15-29 age group.
“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,” she said.
She added: “Suicide must be taken seriously in all respects, from ideation to execution.
“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 utilised, as well as behavioural 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 behavioural alterations.” – By José Tadeu Arantes/Agência FAPESP
