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

• Published in: European neuropsychopharmacology Vol. 23; no. 11; pp. 1530 - 1540
• Main Authors: Brunoni, A.R, Kemp, A.H, Shiozawa, P, Cordeiro, Q, Valiengo, L.C.L, Goulart, A.C, Coprerski, B, Lotufo, P.A, Brunoni, D, Perez, A.B.A, Fregni, F, Benseñor, I.M
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2013
• Subjects: Adolescent; Adult; Aged; Alleles; Brain-Derived Neurotrophic Factor - genetics; Brain-derived neurotrophic factor polymorphism; Combined Modality Therapy - adverse effects; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - genetics; Double-Blind Method; Electric Stimulation Therapy; Epistasis, Genetic - genetics; Female; Humans; Internal Medicine; Major depressive disorder; Male; Middle Aged; Polymorphism, Single Nucleotide - genetics; Psychiatry; Serotonergic Neurons - drug effects; Serotonergic Neurons - physiology; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins - genetics; Serotonin selective reuptake blockers; Serotonin-transporter-linked-polymorphic region; Sertraline - therapeutic use; Single-nucleotide polymorphism; Transcranial direct current stimulation; Treatment Outcome; Serotonin selective reuptake blockers; Single-nucleotide polymorphism; Serotonin-transporter-linked-polymorphic region; Brain-derived neurotrophic factor polymorphism; Transcranial direct current stimulation; Major depressive disorder
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2013.03.009

Abstract 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.