Pharmacogenes Associated with Suicidal Behavior: Addressing a Potential Therapeutic Window

Abstract

Suicide rates in Mexico have been rising, and because suicidal behavior has a genetic component, several pharmacogenes potentially linked with suicide risk have been investigated. This review aims to summarize articles addressing pharmacogenes, their relationship with suicidal behavior phenotypes, and their role in pharmacological treatment response. Among the identified pharmacogenes, variants in genes such as ATP-binding cassette subfamily B member 1 Gene (ABCB1) and FKBP Prolyl Isomerase 5 Gene (FKBP5) have been repeatedly observed across suicide attempt and completed suicide phenotypes. With these we could hypothesize that there is a possibility of finding shared genetic mechanisms among suicide phenotypes. When studying the response to treatment, the presence of certain variants may result in reduced drug response, yielding no benefit and possibly worsening symptoms, potentially culminating in suicidal behavior. Moreover, overlapping variants have been identified between suicidal behavior and altered response to psychotropic drugs in pharmacogenes involved in different functional pathways such as neurotransmission, hypothalamic-pituitary-adrenal (HPA) regulation and neuroinflammation, so this combination could lead to an increased genetic vulnerability to suicidal behavior. In summary, although data on pharmacogenes related to suicide exist, further research is required to replicate findings in the Mexican population. The insights presented in this review may support the inclusion of other pharmacogenes or variants in existing pharmacogenomic panels to advance precision medicine approaching suicide prevention.