Impact of 5-HTTLPR and BDNF polymorphisms on response to sertraline versus transcranial direct current stimulation: Implications for the serotonergic system

Date
2013-11-01Author
Brunoni, A. R.
Kemp, A. H.
Shiozawa, P.
Cordeiro, Q.
Valiengo, L. C. L.
Goulart, A. C.
Coprerski, B. [UNIFESP]
Lotufo, P. A.
Brunoni, D. [UNIFESP]
Perez, A. B. A. [UNIFESP]
Fregni, F.
Bensenor, I. M.
Type
ArtigoISSN
0924-977XIs part of
European NeuropsychopharmacologyDOI
10.1016/j.euroneuro.2013.03.009Metadata
Show full item recordAbstract
Transcranial direct current stimulation (tDCS) has been intensively investigated as a non-pharmacological treatment for major depressive disorder (MDD). While many studies have examined the genetic predictors of antidepressant medications, this issue remains to be investigated for tDCS. in the current study, we evaluated whether the BDNF Val66Met and the 5-HTT (5-HTTLPR) polymorphisms were associated with tDCS antidepressant response. We used data from a factorial trial that evaluated the efficacy of tDCS and sertraline and enrolled 120 moderate-to-severe, antidepressant-free participants. in the present study, we used analyses of variance to evaluate whether the BDNF (Val/Val vs. Met-carries) and 5-HTTLPR alleles (long/long vs short-carriers) were predictors of tDCS (active/sham) and sertraline (sertraline/placebo) response. Analyses were conducted on the polymorphisms separately and also on their interaction. Genotype frequencies were in Hardy-Weinberg equilibrium. BDNF polymorphism was not associated with treatment response. We found that 5-HTTLPR predicted tDCS effects as long/long homozygotes displayed a larger improvement comparing active vs. sham tDCS, while short-allele carriers did not. A dose-response relationship between active-sham differences with the long allele was also suggested. These results strengthen the role of the serotonergic system in the tDCS antidepressant effects and expand previous findings that reported that tDCS mechanisms of action partially involve serotonergic receptors. Therefore, we hypothesize that tDCS is a neuromodulation technique that acts over depression through the modulation of serotonergic system and that tDCS top-down antidepressant effects might not be optimal in brain networks with a hyperactive amygdala inducing bottom-up effects, such as occurs in short-carriers. (C) 2013 Elsevier B.V. and ECNP. All rights reserved.
Citation
European Neuropsychopharmacology. Amsterdam: Elsevier B.V., v. 23, n. 11, p. 1530-1540, 2013.Keywords
Transcranial direct current stimulationMajor depressive disorder
Single-nucleotide polymorphism
Brain-derived neurotrophic factor polymorphism
Serotonin-transporter-linked-polymorphic region
Serotonin selective reuptake blockers
Sponsorship
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Collections
- EPM - Artigos [17701]