P.2.b.020 Comparative analysis of pregabalin and buspirone as adjunctive agents in major depressive disorder partially responsive to SSRIs

Abstract

The aim of the present study was to preliminarily evaluate the role of two genes involved in neuroplastic processes in early response to ADs: the Brain derived neurotrophic factor (BDNF) coding for a major prosurvival factor in the brain, and Sialyltransefarase X (ST8SIA2), which product modulates the adhesive properties of Neural cell adhesion molecule (NCAM). We also tested potential differential effect of genetic variants depending on environmental stress exposure. Methods: The sample was composed by 114 patients affected by Mood or Anxiety disorders, enrolled for treatment with ADs, with at least minor depression (scoring 8 or more at the Hamilton Rating Scale for Depression, HRSD). All patients were asked to fill out a questionnaire for stressful life events (SLEs) designed to evaluate events in young age (less than 15 years old), the year before illness onset, and the month preceding current episode. All the patients were evaluated at baseline and weekly thereafter until the fourth week by the HRSD. Subjects were genotyped for 3 single-nucleotide polymorphisms (SNPs) in BDNF and 5 in ST8SIA. Linkage disequilibrium among SNPs was calculated by Haploview software and haplotypes were obtained by the R-software. The GLM model was employed to test the effect of alleles and haplotypes, crossed with exposure to stress, on % improvement of symptoms from baseline. Results: SLEs did not impact significantly early response to ADs. Alleles in two SNPs in BDNF (rs11030101 A-allele and rs11030104 G-allele) and alleles in two SNPs in ST8SIA2 (rs11853992-A allele and rs17522085-T) were associated to a slower response to ADs only if non-exposed to onset SLEs, whilst they had a similar response compared to the carriers of the opposite variant if exposed to onset SLEs (all p< 0.007). Haplotype analyses confirmed these trends. Conclusions: According to our data, variants in BDNF and ST8SIA may influence differentially the early response to ADs depending on exposure to SLEs at illness onset. Exposure to stress may impact the transcriptional activity of genes through epigenetic mechanisms, resulting in unexpected phenotypes. Further, recent animal studies reported that an over expression of BDNF may have detrimental effects [1], and some studies in humans found heterozygous for the most investigated BDNF rs6265 SNP having a better response to ADs [2]. The complex interplay between genetic effects, environmental factors, as well as other biological systems deserves further investigation by means of sophisticated methods of investigation.