Pharmacogenetic Association Between Glutamatergic Genes and Sri Treatment Response in Obsessive Compulsive Disorder

Abstract

IntroductionPharmacogenetic studies in obsessive-compulsive disorder (OCD) primarily focussing on serotonergic and dopaminergic polymorphisms, provided inconsistent findings. There is recent evidence for glutamatergic abnormalities in OCD.AimsExamine the association glutamatergic genes with serotonin reuptake inhibitor (SRI) response in OCD.ObjectivesTo study pharmacogenetic association between SLC1A1 and GRIN2B polymorphisms with SRI response in OCD.MethodsDSM-IV OCD patients were recruited from a specialty OCD clinic and evaluated using the Yale-Brown obsessive compulsive scale (YBOCS), Mini International Neuropsychiatric Interview (MINI) plus, Clinical Global Impression scale (CGI). They were subsequently reassessed with YBOCS and CGI. To study extreme phenotypes, we included only full responders (> 35% YBOCS improvement and CGI-I score of 1 or 2) to any SRI (n = 191) and non-responders (< 25% YBOCS improvement and CGI-I score ≥ 4) to adequate trial of at least two SRIs (n = 84). Partial responders were excluded. Genotyping was performed using an ABI9700 PCR machine.ResultsGenotype frequencies did not deviate significantly from the values predicted by the Hardy-Weinberg equation. Case-control association analyses revealed no significant association between genotype/allele frequencies with SRI response.ConclusionOur data does not show any association between polymorphisms in glutamatergic genes and SRI response in OCD though such associations have been found in other studies. More SNP's in the same gene could be responsible for the pharmacogenetic associations. More homogenous sample considering symptom dimensions and other phenotypic variables may be needed. It may be critical to go beyond “usual suspect” candidate gene research. In this regard, a novel approach to identify SRI response biomarkers is the use of cellular models.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene–environment interaction approach

“…With respect to the regression analysis, PRS was not a predictor for treatment response in our sample. Some evidences exist about the non-shared genetic bases of OCD risk and OCD treatment response 22,55 . In addition, although other studies have found an association between OCD treatment response and genes previously associated to OCD risk 14,15,19 (such as SLC1A1, SLC6A4 or BDNF 12,13 ), to our knowledge, only one genetic variant (rs3087879 in SLC1A1 gene) has been related to both OCD treatment response (a greater resistance) and OCD risk 12 .…”