Do testosterone and brain-derived neurotrophic factor interactions play a role in the pathophysiology of suicidal behavior?

To the Editor

Suicide is a serious medical and social affliction that has severe emotional recourse for all persons involved. This phenomenon occurs in approximately one million people worldwide every year and has both psychological and neurobiological facets. Understanding the neurobiology of such a devastating event has been the focus of many recent research projects. Multiple lines of evidence suggest that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of suicide. For example, one such study revealed that patients with depression and suicidal behavior had lower plasma levels of BDNF (Sher, 2011). Another study showed decreased levels of BDNF in the hippocampus and prefrontal cortex in post-mortem brains of patients who had committed suicide (Sher, 2011).

Testosterone is another neurobiological marker that has been implicated in suicidal behavior. For example, in a comparison of healthy men with men after a suicide attempt, significantly lower testosterone levels were found in the suicide attempters (Sher, 2012). Another study showed that males who had attempted suicide had lower plasma testosterone levels than males who were hospitalized for unintentionally falling from high heights (Sher, 2012).

Although BDNF and testosterone are independently involved in the neurobiology of suicide, several studies have been developed to investigate any possible interactions between the two. For example, it has been shown that BDNF expression in the striatal and frontal cortical brain regions of rats had a directly positive correlation with testosterone surges prior to adolescence and that androgen receptor activation caused significant changes in BDNF expression and signaling during adolescence (Hill et al., 2012). A similar study concluded that after gonadectomy, male rats exhibited reduced expression of BDNF during adolescence (Carbone and Handa, 2013). In a human clinical trial, administration of testosterone to patients suffering from multiple sclerosis resulted in an increase of BDNF localized to white matter lesions (Gold et al., 2008).

In studying the neurobiology of suicidal behavior, studies have shown that BDNF and testosterone each play important roles. Several studies have recently been attempting to find a connection between BDNF and testosterone, with results indicating that they do in fact interact. Our hypothesis is that this interaction between BDNF and testosterone is important in uncovering the neurobiological aspect of suicidal behavior. Further understanding of specific mechanisms of interaction may contribute to suicide prevention in the future.