Association between FKBP5 and CRHR1 genes with suicidal behavior: A systematic review

• Suicide is a serious public health problem worldwide with an estimated annual mortality rate of 14.5 deaths per 100,000 people.
• FKBP5 and CRHR1 genes have been associated importantly with epigenetic alterations in molecular pathways of the function HPA axis and serotonergic system in patients with suicidal behavior.
• An understanding of the functional consequence of FKBP5 and CRHR1 genes and its polymorphisms from a neuropathological perspective would be convenient to advance our understanding of their role in the HPA axis alterations with suicidal behavior.

Suicide is one of the leading causes of death around the world with approximately one million suicides per year. An increasing number of neurobiological studies implicate HPA system dysfunction in suicide behavior, stimulating genetic research to focus on genes related to this system. This systematic review was focused on searching a correlation between FKBP5 and CRHR1 genes with suicidal behavior. Therefore, an electronic search strategy, using PubMed, EBSCO and Cochrane Library databases, was conducted from the inception of the studies into the databases to July 2016. The inclusion criteria were: use of at least one analysis investigating the relation between either the genetic variants in FKBP5 and/or CRHR1 genes with suicidal behavior. 2) use of a case–control design; 3) investigation about suicidal behavior in the form of suicide completion or history of at least one suicide attempt, as defined by each individual study; 4) inclusion of samples comprising control subjects; and 6) inclusion of reports written only in English language. The PRISMA guidelines were followed and the search strategy ensured that all possible studies were identified to compile the review. Using the keyword combinations, the search strategy provided 3334 articles, of which only 15 case-control studies were included in this systematic review. The included studies comprised 2526 subjects with suicidal behavior. A quantitative synthesis of results from the included studies was not undertaken due to marked methodological heterogeneity. This review showed a significant genetic association in most studies in FKBP5 and CRHR1 genes with a high rate of attempted suicide, pointing out that the expression of these genes and its polymorphisms could be a key predictor of suicide risk. In conclusion, this systematic review supports an association between suicidal behavior and genetic variants in FKBP5 and CRHR1 genes.