Association of BDNF, HTR2A, TPH1, SLC6A4, and COMT polymorphisms with tDCS and escitalopram efficacy: ancillary analysis of a double-blind, placebo-controlled trial

Abstract

Objective: We investigated whether single nucleotide polymorphisms (SNPs) associated with neuroplasticity and activity of monoamine neurotransmitters, such as the brain-derived neurotrophic factor (BDNF, rs6265), the serotonin transporter (SLC6A4, rs25531), the tryptophan hydroxylase 1 (TPH1, rs1800532), the 5-hydroxytryptamine receptor 2A (HTR2A, rs6311, rs6313, rs7997012), and the catechol-O-methyltransferase (COMT, rs4680) genes, are associated with efficacy of transcranial direct current stimulation (tDCS) in major depression. Methods: Data from the Escitalopram vs. Electrical Current Therapy for Treating Depression Clinical Study (ELECT-TDCS) were used. Participants were antidepressant-free at baseline and presented with an acute, moderate-to-severe unipolar depressive episode. They were randomized to receive escitalopram/tDCS-sham (n=75), tDCS/placebo-pill (n=75), or placebo-pill/sham-tDCS (n=45). General linear models assessed the interaction between treatment group and allele-wise carriers. Additional analyses were performed for each group and each genotype separately. Results: Pairwise group comparisons (tDCS vs. placebo, tDCS vs. escitalopram, and escitalopram vs. placebo) did not identify alleles associated with depression improvement. In addition, exploratory analyses also did not identify any SNP unequivocally associated with improvement of depression in any treatment group. Conclusion: Larger, combined datasets are necessary to identify candidate genes for tDCS response.

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

“…The impact of our findings on further genomic evidence for the treatment of alcohol use disorders is potentially interesting. Genotyping has been considered as a possible tool for precision medicine, with a special focus in the area of mental health [38][39][40][41]. Even if many studies supported the genotyping OPRM1 in the treatment with naltrexone [42][43][44], our data would suggest genotyping for ADH1B, ADH1C and ALDH2 before the treatment.…”

BDNF Genetic Variant and Its Genotypic Fluctuation in Major Depressive Disorder

“…Interestingly, Korean participants presented mixed results [54][55][56][57], demonstrating a lack of consensus on this association. Although no significant association between the BDNF genetic variant and the "attempted suicide" variable in a Chinese study (p = 0:807), Brunoni et al [19] found low BDNF protein serum levels might be related to attempted suicide [22].…”

“…When observing only the BDNF Val66Met (rs6265) genetic variant frequency and genotypic distribution (Table 1), the GG (Val/Val) genotype was frequent in more than 50% of the MDD sample studied in 65% of the analyzed studies [17,18,19,21,23,25,26,[30][31][32][33] (Figure 3). Its frequency is lower in only few studies [16,20,22,[27][28][29].…”

“…Antidepressant use might affect the BDNF protein serum levels [19,20]. Froud et al [21] found that the recent use of antidepressants in the last 12 months was a substantial factor for changes in the BDNF protein serum levels.…”

Effect of Catechol-O-Methyltransferase Genotype Polymorphism on Neurological and Psychiatric Disorders: Progressing Towards Personalized Medicine

“…The results indicated non-significant dose-dependent effects of the Met allele and lower tDCS vs. placebo effects. The study noted the limitation of a small sample size resulting in non-significant findings [ 37 ]. In 2020, another RCT investigating the neurocognitive effects of tDCS treatment in 130 participants with unipolar or bipolar depression determined COMT and BDNF genotype polymorphisms as potential moderators of neurocognitive effects.…”