Pharmacogenomics of Suicidal Events

Abstract

Pharmacogenomic studies of antidepressant treatment-emergent suicidal events in depressed patients report associations with polymorphisms in genes involved in transcription (CREB1), neuroprotection (BDNF and NTRK2), glutamatergic and noradrenergic neurotransmission (GRIA3, GRIK2 and ADRA2A), the stress and inflammatory responses (FKBP5 and IL28RA), and the synthesis of glycoproteins (PAPLN). Nearly all of the reported events in these studies were modest one-time increases in suicidal ideation. In 3231 unique subjects across six studies, 424 (13.1%) patients showed increases in suicidal ideation, eight (0.25%) attempted suicide and four (0.12%) completed suicide. Systems related to most of these genes have also been implicated in studies of suicidal behavior irrespective of treatment. Future pharmacogenomic studies should target events that are clinically significant, related clinical phenotypes of response and medication side effects, and biological pathways that are involved in these outcomes in order to improve treatment approaches.

KEYWORDS::

• antidepressant
• depression
• genetics
• pharmacogenomics
• suicidal ideation
• suicide
• treatment

Financial & competing interests disclosures

This work was supported by a NARSAD Distinguished Investigator Award (David Brent, MD); NIMH grants MH61835, MH56612 (David Brent, MD); MH77930 (Nadine Melhem, PhD); and CIHR#151060 (Gustavo Turecki, MD, PhD). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by a NARSAD Distinguished Investigator Award (David Brent, MD); NIMH grants MH61835, MH56612 (David Brent, MD); MH77930 (Nadine Melhem, PhD); and CIHR#151060 (Gustavo Turecki, MD, PhD). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.