Suicidal ideation during antidepressant treatment: do genetic predictors exist?

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• Clinical risk factors do not predict suicidal events during antidepressant treatment.
• Pharmacogenomic studies explore genetic variants for predicting individual susceptibility to suicidal ideation.
• Several genes related to neurotransmitter systems and brain function have been implicated.

Purpose of the Study:

• To review current pharmacogenomic research on predicting suicidal ideation during antidepressant treatment.
• To highlight potential genetic predictors and methodological challenges in the field.

Main Methods:

• Review of candidate gene and genome-wide association studies.
• Analysis of genes involved in neurotrophic, synaptic plasticity, noradrenergic, glutamatergic, inflammatory, and HPA axis systems.
• Discussion of methodological limitations in current research.

Main Results:

• Several genes (e.g., CREB1, BDNF, NTRK2, ADRA2A, GRIA3, GRIK2, GDA, IL28RA, FKBP5, PAPLN, APOO, KCNIP4, ELP3) have been associated with antidepressant-induced suicidal ideation.
• Findings require validation in phenotypically well-designed samples.
• Methodological issues include inconsistent phenotype definitions and lack of clinically significant suicidal events.

Conclusions:

• Pharmacogenomic studies have not yet fulfilled their promise in predicting suicidal ideation.
• Future research needs to focus on clinically significant events and robust phenotyping.
• Antidepressants generally show a beneficial effect on suicidal ideation, encouraging their prescription.