Role of serotonergic gene polymorphisms on response to transcranial magnetic stimulation in depression

Zanardi, Raffaella; Magri, Lorenzo; Rossini, David; Malaguti, Alessia; Giordani, Silvia; Lorenzi, Cristina; Pirovano, Adele; Smeraldi, Enrico; Lucca, A.

doi:10.1016/j.euroneuro.2007.03.008

Cited by 48 publications

(39 citation statements)

References 42 publications

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“…45,46 Two out of three rTMS studies also found that it was associated with antidepressant response. [47][48][49] In SELECT-TDCS we also found that it was associated with a larger active-sham difference.…”

Section: -41supporting

confidence: 50%

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

et al. 2015

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CONTEXT AND OBJECTIVE: Major depressive disorder (MDD) is a common psychiatric condition, mostly treated with antidepressant drugs, which are limited due to refractoriness and adverse effects. We describe the study rationale and design of ELECT-TDCS (Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study), which is investigating a non-pharmacological treatment known as transcranial direct current stimulation (tDCS). DESIGN AND SETTING: Phase-III, randomized, non-inferiority, triple-arm, placebo-controlled study, ongoing in São Paulo, Brazil. METHODS: ELECT-TDCS compares the efficacy of active tDCS/placebo pill, sham tDCS/escitalopram 20 mg/day and sham tDCS/placebo pill, for ten weeks, randomizing 240 patients in a 3:3:2 ratio, respectively. Our primary aim is to show that tDCS is not inferior to escitalopram with a non-inferiority margin of at least 50% of the escitalopram effect, in relation to placebo. As secondary aims, we investigate several biomarkers such as genetic polymorphisms, neurotrophin serum markers, motor cortical excitability, heart rate variability and neuroimaging. RESULTS: Proving that tDCS is similarly effective to antidepressants would have a tremendous impact on clinical psychiatry, since tDCS is virtually devoid of adverse effects. Its ease of use, portability and low price are further compelling characteristics for its use in primary and secondary healthcare. Multimodal investigation of biomarkers will also contribute towards understanding the antidepressant mechanisms of action of tDCS. CONCLUSION: Our results have the potential to introduce a novel technique to the therapeutic arsenal of treatments for depression. CLINICAL TRIAL REGISTRATION: ClinicalTrials.Gov NCT01894815. RESUMOCONTEXTO E OBJETIVO: O transtorno depressivo maior (TDM) é uma condição psiquiátrica comum, tratada com medicamentos antidepressivos, os quais são limitados devido à refratariedade e efeitos adversos. Descrevemos o racional e o desenho do Estudo Clínico Escitalopram versus Eletroterapia no Tratamento da Depressão (ELECT-TDCS), que investiga um tratamento não farmacológico, conhecido como estimulação transcraniana por corrente contínua (ETCC). DESENHO E LOCAL: Ensaio de fase III, randomizado, de não inferioridade, de três braços, placebo-controlado, em execução em São Paulo, Brasil. MÉTODOS: O estudo compara a eficácia da ETCC ativa/pílula placebo, ETCC simulada/escitalopram 20 mg/dia e ETCC simulada/pílula placebo durante 10 semanas, randomizando 240 pacientes em uma proporção 3:3:2, respectivamente. O objetivo principal é demostrar que a ETCC não é inferior ao escitalopram com uma margem de não inferioridade de pelo menos 50% do efeito de escitalopram em relação ao placebo. Como objetivos secundários, investigamos biomarcadores como polimorfismos genéticos, marcadores séricos, excitabilidade cortical motora, variabilidade da frequência cardíaca e neuroimagem. RESULTADOS: Provar que ETCC é igualmente eficaz a antidepressivos teria um tremendo impacto na psiquiatria clíni-ca...

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Section: -41supporting

confidence: 50%

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

et al. 2015

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“…There is a well-documented history of expectancy effects in this population, and we do not know what the rate of nonspecific or non-drug-attributable responses occurred in this sample. Some have suggested that there may be an association between 5-HTTPLR polymorphisms and response to multiple interventions; specifically, there is speculation that patients with the L/L genotype tend to have stronger expectancy responses to any treatment (for instance, in depression to light therapy, sleep deprivation, transcranial stimulation, or placebo) (Benedetti et al, 2003; Zanardi et al, 2007). The expectancy could, of course, be related to genetic variation of the parents, but we did not draw samples from parents in this study.…”

Section: Discussionmentioning

confidence: 99%

A pharmacogenetic study of escitalopram in autism spectrum disorders

et al. 2009

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Scientific AbstractObjective-To determine the effect of serotonin transporter polymorphism promoter region (5-HTTPLR) genotypic variation (low, intermediate, and high expression groups) on response to escitalopram treatment of children and adolescents with Autism Spectrum Disorders (ASDs).Method-The study used a forced titration, open label design, with genotype blind until study completion. Participants were children and adolescents aged 4 to 17 years of age with a confirmed ASD (Autistic Disorder, Asperger's Disorder, or Pervasive Developmental Disorder, Not Otherwise Specified).Results-There was an interaction between genotype group and time on the Aberrant Behavior Checklist Irritability Subscale (primary outcome variable) (linear MMLE = −4.84, Z = −2.89, SE = 1.67, p = 0.004). Examination of baseline to last-observation carried forward scores revealed that a genotype grouping based on a previous study of platelet 5-HT uptake revealed less response in the genotype group that had S/S genotype for 5-HTTLPR and did not have a diplotype in intron 1 previously shown to be associated with increased platelet 5-HT uptake.Conclusion-This genotype-blind, prospective pharmacogenetic study found the group of subjects with associated with the lowest platelet 5-HT uptake from previous study had the smallest reduction in ABC-Irritability scores after open label treatment with escitalopram. Replication is necessary to confirm these findings.Lay Abstract-Many children with Autism Spectrum Disorders have problems with anxiety, obsessions, compulsions, and insisting that things stay the same. When other interventions are not adequately helping the child deal with these difficulties, sometimes medication is considered a treatment option. There continues to be some difficulties associated with the use of SSRIs for a substantial proportion of individuals. A substantial minority of children with ASDs will become activated (drug-induced insomnia, hyperactivity, and/or general disinhibition) on these medications, even at low doses McDougle et al., 2000;Owley et al., 2005). Dosing is also complicated by the fact that there appears to be no relationship between weight and final dose, and only a weak correlation between age and final dose (Owley et al., 2005).A pharmacogenetic study was conducted to determine if variation in the gene that codes for the primary protein target of SSRIs, the serotonin transporter, would be related to escitalopram response or final dose. A complex insertion/deletion/single nucleotide containing polymorphism in the promoter region of the transporter (5-HTTLPR), thought be related to 5-HTT gene expression, was chosen as the primary candidate polymorphism (Heils et al., 1996;Hu et al., 2006).Only one study has looked at the SSRI treatment as a function of 5-HTTPLR in ASDs. In a double-blind study of outcome using the SSRI fluvoxamine in a group of 18 children diagnosed with autism using DSM-IV (APA, 1994) criteria only, Sugie and colleagues (Sugie et al., 2005) found the L/L and S/L groups to have superior ou...

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“…Several studies have found that polymorphisms within the genes that encode serotonin (5-HT) carriers, 5-HT 1A receptors (Zanardi et al, 2007), and brain-derived neurotrophic factor (BDNF) (Cheeran et al, 2008) influence a patient’s response to therapy. An investigation of the polymorphism within the 5-HT 1A receptor gene ( n = 99; Zanardi et al, 2007) found that C/C patients are more susceptible to TMS therapy than C/G and G/G patients. Another clear illustration of the dependence between genetic polymorphisms and the benefits of TMS is the difference between subjects with the Val66Met and Val66Val alleles of the BDNF gene (Cheeran et al, 2008).…”

Section: Effects Of Rtms On the Genetic Apparatus Of Neuronsmentioning

confidence: 99%

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

Chervyakov

Chernyavsky

Синицын

et al. 2015

Front. Hum. Neurosci.

291

184

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Transcranial magnetic stimulation (TMS) is an effective method used to diagnose and treat many neurological disorders. Although repetitive TMS (rTMS) has been used to treat a variety of serious pathological conditions including stroke, depression, Parkinson’s disease, epilepsy, pain, and migraines, the pathophysiological mechanisms underlying the effects of long-term TMS remain unclear. In the present review, the effects of rTMS on neurotransmitters and synaptic plasticity are described, including the classic interpretations of TMS effects on synaptic plasticity via long-term potentiation and long-term depression. We also discuss the effects of rTMS on the genetic apparatus of neurons, glial cells, and the prevention of neuronal death. The neurotrophic effects of rTMS on dendritic growth and sprouting and neurotrophic factors are described, including change in brain-derived neurotrophic factor concentration under the influence of rTMS. Also, non-classical effects of TMS related to biophysical effects of magnetic fields are described, including the quantum effects, the magnetic spin effects, genetic magnetoreception, the macromolecular effects of TMS, and the electromagnetic theory of consciousness. Finally, we discuss possible interpretations of TMS effects according to dynamical systems theory. Evidence suggests that a rTMS-induced magnetic field should be considered a separate physical factor that can be impactful at the subatomic level and that rTMS is capable of significantly altering the reactivity of molecules (radicals). It is thought that these factors underlie the therapeutic benefits of therapy with TMS. Future research on these mechanisms will be instrumental to the development of more powerful and reliable TMS treatment protocols.

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Role of serotonergic gene polymorphisms on response to transcranial magnetic stimulation in depression

Cited by 48 publications

References 42 publications

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

The Escitalopram versus Electric Current Therapy for Treating Depression Clinical Study (ELECT-TDCS): rationale and study design of a non-inferiority, triple-arm, placebo-controlled clinical trial

A pharmacogenetic study of escitalopram in autism spectrum disorders

Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation

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