FKBP5 Gene Variants as Predictors for Antidepressant Response in Individuals with Major Depressive Disorder Who Have Experienced Childhood Trauma. A Systematic Review

FKBP5 gene variants may predict antidepressant treatment response in individuals with Major Depressive Disorder. PubMed and Web of Science were searched systematically for articles studying individuals who had received a diagnosis of Major Depressive Disorder (MDD) and were given antidepressant treatment. Inclusion criteria were studies that researched FKBP5 and its variants and focused on antidepressant treatment response. Previous studies support a potential underlying epigenetic mechanism, demethylation at FKBP5 polymorphisms (rs1360780, rs3800373, rs9470080, and rs4713916) after experiencing childhood trauma, leading to increased hypothalamic-pituitary-adrenal (HPA) axis sensitivity and a propensity for the development of MDD. These polymorphisms informed the search, but additional polymorphisms (rs9380514, rs352428) were also considered. Studies conducted prior to 2008, reviews, meta-analyses, editorials, and non-research based articles were excluded. Studies examined in this article link FKBP5 polymorphisms (rs4713916) and FKBP5 RNA levels with positive antidepressant response. Variants rs1360780, rs3800373, and rs9470080 were associated with both positive response and non-response or lack of remission. Variants rs9380514, rs352428, and rs936882 were associated with poor response to antidepressant treatment or non-remission. Further insights into the role FKBP5 plays in development and antidepressant treatment response may be aided by future studies focused on individuals who previously experienced childhood trauma and later developed MDD.