To keep in mind National Suicide Prevention Suicide Week as well as to offer some hopeful news, this week’s post summarizes a recent study from the American Journal of Psychiatry that claims to have found a gene that is related to suicidal behavior. It is somewhat of a complicated study with multiple samples (it’s hard to publish single gene studies anymore without an independent replication sample) and 
associations related both to the actual gene and its DNA code as well as epigenetic differences in the amount of methylation the gene has undergone: all of which in turn affects how much of the gene product is expressed. The gene under scrutiny is involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function: a key factor in a body’s response to stress. Previous research in both animals and humans has suggested that genes involved in this process might be an important place to look.
This study used prefrontal cortex tissue from several brain banks that included many individuals with depression, some of whom died by suicide. Possible candidate genes that emerged were then validated in tissue from other individuals as well as gene expression analyses from three groups of living patients (coming from blood not brain, obviously), where levels of anxiety and stress were assessed as well as concentrations of salivary cortisol.
The signal for suicide and suicidal behavior was found to be related to the SKA2 gene on chromosome 17. As mentioned, a significant association was found both related to DNA, specifically a single nucleotide polymorphism (SNP) at location rs7208505, and more strongly to epigenetic changes of that gene. Here, increased methylation was related to higher rates of suicide as well as higher rates of suicidal behavior. The accuracy of predicting suicidal behavior from these genetic and epigenetic variations in the living group was quite high at 80%, particularly the progression from suicidal ideation into attempt. However, this number comes from complicated statistical models and does not lend itself to an easy yes/no prediction of suicidal behavior based on the result of simple blood test.
The authors concluded that the SKA2 gene and its level of epigenetic changes may be an important biomarker for suicidal behavior. In saying this, however, it is important to remember that the term “suicide gene,” just like an “ADHD gene” or a “depression gene” is really a misnomer, as genes don’t code for diseases per se but rather for products involved in some kind of brain activity. In this case, the SKA2 gene is thought to help “chaperone” a glucocorticoid receptor (which may play an important step in regulating down the stress response) to the nucleus and can thus play a role in HPA axis function. While certainly an important and thought provoking study, the authors cautioned that their sample size was small and results should be considered preliminary. Lest people also start thinking that certain people are destined to be depressed and suicidal, it is also important to note that epigenetic changes to genes such as the ones found to be important in this study can be strongly related to the quality of one’s environment.
Reference
Guintivano J, et al. Identification and Replication of a Combined Epigenetic and Genetic Biomarker Predicting Suicide and Suicidal Behaviors. Am J Psychiatry 2014, epub ahead of print.
Tags: depression, ska2, suicide, suicide gene