Curator's Favorite Papers

Genetics has been shown to have a profound effect on response to treatment in patients with major depressive disorder (MDD) and may account for as much as 42% of the variability in treatment response, according to some studies. In addition, personality traits, as defined by “the Big-Five" (openness, conscientiousness, extraversion, agreeableness, and neuroticism), which are likely to also be influenced by genetics, may also associate with response to anti-depression treatment. A new study (Association of the Polygenic Scores for Personality Traits and Response to Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder) intended to uncover gene variants associated with the cross-trait associations between “the Big-Five” and treatment response using data from the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (N = 529) and the International SSRI Pharmacogenomics Consortium (N = 865). Evidence points to an overlap in association between specific personality traits and SSRI treatment outcomes and that the association is partly due to genetics. Specifically, the study evaluated the combined effect of multiple genes (polygenic score, PGS) and their association with one of the five personality traits, as well as response and remission in patients with MDD who are prescribed SSRIs. The PGS for openness personality with treatment response was statistically significant in the ISPC cohort and statistically significant with remission in the PGRN-AMPS sample. PGS for conscientiousness was associated with response, but not remission. Cross-trait meta-analysis of GWAS uncovered eight overlapping genetic loci with previously reported associations with response to SSRIs as well as certain personality traits, particularly neuroticism.  Of note, several PharmGKB members were co-authors on this study: Katrin Sangkuhl, Scientific Curator, Ryan Whaley, Technical Lead, Russ Altman, Co-PI of PharmGKB and Teri Klein, Director and Co-PI of PharmGKB. You can find more information about pharmacogenetic guided dosing for SSRIs on cpicpgx.org as well as on the PharmGKB annotation of the CPIC Guideline for SSRIs and CYP2D6 and CYP2C19.