The Dark Side of our Brain

Everyone knows the feeling of being in a hopeless situation. That there is no good solution of getting out of that situation. Still, most of the time we, or our brain comes up with an idea to solve the problem, to move on. Sometimes it’s as simple as not thinking about the situation, sometimes it’s an eloquent solution even we ourselves are surprised that we could think of something so good. However, this is not always the case. In some, still too many, cases the hopelessness is so profound that we do not see a way out, except one. These intense experiences of hopelessness cannot be compared to what we might experience in everyday life, as its experience is often described as more severe and more extensive than everyday sadness. From a biological viewpoint, suicide and suicidal thoughts are quite contradictory the idea of self-preservation: why would a human brain decide that it shouldn’t exist anymore?

This statement sounds a bit over-simplified, however, according to recent evidence and review papers, there are certain biological differences in brain factors between suicide victims and other deceased individuals. However, during this discussion of possible biological explanations, it must be kept in mind, that suicide is a complex event that cannot be explained by one single biological difference. It is a combination of events in the personal history, biological vulnerability, societal factors and trigger situations. It is often a combination of long-lasting helplessness and impulsive behavior and unfortunately it is not always predictable. This complexity would not fit into one post, therefore I want to refer to this extensive review of the “molecular basis of the suicidal brain” by Gustavo Turecki for a more complete picture of the complex interactions of biological and social explanations for suicidal behavior. It gives a detailed overview of predisposing factors like family history, developmental factors like changes in the HPA-Axis (“stress-axis”) and proximal factors like acute substance abuse.

Suicide is difficult and delicate topic, however, it is more common than we believe and more common than it needs to be: according to the WHO more than 800.000 individuals die of suicide each year and there are many more attempts and display of suicidal behavior. These numbers and the fact that suicide is often preventable calls for finding certain factors identifying individuals who are at a higher risk of suicide. Since suicidal behavior is part of the symptomatology of many psychopathologies (e.g. depression and schizophrenia), a biological biomarker for a risk population of these patients seems as one of many necessary or and possible ways to effectively reduce the number of suicides.

Source

One line of research focuses on changes in brain plasticity, or more specifically epigenetic changes in genes that code neural growths or neural regeneration, like the brain derived neurotropic factor (BDNF), a protein that plays an important role in processes underlying neural plasticity. As it is an important factor in the biology of Depression, which symptomatology includes suicidal behavior, it seems reasonable to investigate its role in the biology of suicidality. Dwivedi and colleagues (2003) found differences in gene expression for BDNF in brains of suicide victims and controls (no psychiatric diagnosis): the expression for BDNF was reduced in individuals that had died of suicide. And, interestingly, the reduced expression did not differ between victims with Major Depression diagnosis and none or other psychiatric diagnosis. Furthermore, the researchers also found a reduced gene expression for the BDNF receptor (trkB). These finding were made in two investigated regions, the prefrontal cortex and the hippocampus, which are relevant regions in cognitive control and learning/memory, respectively. They concluded, that since BDNF is involved in neural plasticity processes like neural regeneration, a reduced gene expression can cause this system to degenerate, making adaption to and coping with critical situations more difficult and less efficient.  A genome wide analysis of suicide victims by Labonté and colleagues (2013) also revealed genetic alterations related to memory and learning, as well as impulsivity.

BDNF seems thus to play a key role in the psychopathology and symptomatology of suicide raising the question of a cause for these epigenetic changes. Other studies that support Dwivedi’s findings therefor extend their research to possible causes of reduced BDNF gene expression. In 2009 Roth and colleagues showed, that young rats, that have been maltreated by their (stressed) mothers, had a lowered BDNF gene expression compared to young rats that did not experience maltreatment. Similar epigenetic marks as suicide completers. As up to 73% (depending on study and inclusion criteria, compare Turecki, 2014) of individuals displaying suicidal behavior report childhood abuse, this can be interpreted as a possible explanation of the change in BDNF. Additionally, these epigenetic changes were passed on to the next generation, making an experienced trauma not only relevant for the person experiencing it but also for the following generation. These long-lasting epigenetic changes might be a way via which temporally distant events like early childhood maltreatment impact adult psychopathology, including suicide.

However, suicide is more complex than methylation changes in one gene related to neuroplasticity. The aforementioned review by Turecki shows this multi-causality of the neurobiology of suicide. Besides the cognitive difficulties connected to changes in BDNF gene expression, impulsivity seems to play a second, just as important role in suicidal behavior. The recent genome wide analysis (by Labonté and colleagues) of suicide victims showed changes in multiple genes, suggesting a vulnerability to suicide caused by a network of gene alterations in the brain. These researchers found changes in genes associated with learning and memory as well as genes associated with heightened anxiety and impulsivity. For now, we can only conclude, that suicide is the result of a complex interaction of biological factors than impact behavior and experiences which in turn may alter biological factors again via epigenetic changes. Still it leaves us with multiple options to treat and prevent suicidal behavior via pharmacotherapy as well as other forms of therapy.

Disclaimer: This post deals with a scientific perspective of possible biological factors for suicidal thoughts and behavior. It is by no means meant as information or help if the reader experiences suicidal thoughts or behavior. If You or a loved one experiences these thoughts, please seek help from a medical professional or call a help hotline (in Germany: 0800 111 0 111 or find numbers of international hotlines on this side).

Title image: https://www.behance.net/gallery/6667239/nature

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