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Protein variant may help predict antidepressant outcomes

According to findings published in The American Journal of Psychiatry, a single-nucleotide polymorphism within the corticotropin-releasing hormone binding protein, or CRHBP, gene may play a role in predicting antidepressant treatment response.

“Although genetic variation within [hypothalamic-pituitary-adrenal (HPA)] axis genes (including those for [corticotropin-releasing hormone] and its receptors) has been linked to depression risk and prognosis, it remains unknown whether genetic variation within the HPA axis contributes to a differential prediction of outcomes for specific types of antidepressants,” Chloe P. O’Connell, BS, from the department of psychiatry and behavioral sciences at Stanford University, and colleagues wrote in The American Journal of Psychiatry. “The precise interaction between genetics and treatment response has yet to be fully explored.”

The investigators examined whether variation within HPA axis genes contributes to symptom outcomes following antidepressant treatment in major depression, and whether this prediction was related to antidepressant type within two large clinical trials.

Using data from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) trial, they assessed 636 patients who completed baseline and 8-week follow-up visits to test the relationship between genotype at 16 candidate HPA axis single-nucleotide polymorphisms (SNPs) and treatment outcomes for three common antidepressants — escitalopram, sertraline and extended-release venlafaxine. They used the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study of outcome predictors in treatment-naive patients with major depression to validate the findings.

Analysis showed that the rs28365143 variant found within the CRHBP gene predicted antidepressant outcomes for remission, response and symptom change, they wrote. Among patients homozygous for the G allele of rs28365143, researchers observed greater remission rates, response rates and symptom reductions. The results were drug-class specific, with patients homozygous for the G allele responding significantly better to escitalopram and sertraline compared with A allele carriers. However, there was no relationship between the rs28365143 genotype and treatment outcomes for venlafaxine. The effect of genotype on treatment response remained the same after stratifying by race. The genotype was also linked to beneficial antidepressant outcomes in the validation sample.

“This work supports a potential role for the SNP rs28365143 within CRHBP in predicting response to pharmacotherapy for depression,” the authors wrote. “Further work is necessary to understand whether the effect of this SNP pertains to other therapies for major depression, such as [electroconvulsive therapy] and cognitive-behavioral therapy. Overall, pharmacogenomics appears to be a promising avenue for the personalization of psychiatric pharmacotherapy, specifically through targeted genotyping.” – by Savannah Demko

Disclosures: O’Connell reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.