RATIONALE: Antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) has been shown to depend on functional polymorphisms within the promoter region of the serotonin transporter gene (5-HTTLPR). This gene gives rise to a biallelic polymorphism designated long (l) and short (s). Homozygosity for the long variant (ll-genotype) is associated with a two times more efficient 5-HT uptake compared to the s/l- or s/s-genotype. Paired pulse transcranial magnetic stimulation is a feasible tool in detecting changes of motor cortex excitability induced by SSRIs. OBJECTIVE: Our study aimed to measure neuromodulatory effects of SSRIs on cortical excitability in healthy volunteers characterized by distinct genotypes of the 5-HTTLPR. METHODS: Cortical excitability was determined in eight genetically defined subjects pre- and post-ingestion of 60 mg citalopram. RESULTS: Subjects with the ll-genotype of the 5-HTTLPR showed a significant enhancement of a particular component of motor cortex excitability (intracortical inhibition) as compared to volunteers without the ll-genotype. CONCLUSION: Distinct neuromodulatory effects after intake of citalopram based on allelic variations of the 5-HTTLPR may explain variable response of patients treated with SSRIs.
RATIONALE: Antidepressant efficacy of selective serotonin reuptake inhibitors (SSRIs) has been shown to depend on functional polymorphisms within the promoter region of the serotonin transporter gene (5-HTTLPR). This gene gives rise to a biallelic polymorphism designated long (l) and short (s). Homozygosity for the long variant (ll-genotype) is associated with a two times more efficient 5-HT uptake compared to the s/l- or s/s-genotype. Paired pulse transcranial magnetic stimulation is a feasible tool in detecting changes of motor cortex excitability induced by SSRIs. OBJECTIVE: Our study aimed to measure neuromodulatory effects of SSRIs on cortical excitability in healthy volunteers characterized by distinct genotypes of the 5-HTTLPR. METHODS: Cortical excitability was determined in eight genetically defined subjects pre- and post-ingestion of 60 mg citalopram. RESULTS: Subjects with the ll-genotype of the 5-HTTLPR showed a significant enhancement of a particular component of motor cortex excitability (intracortical inhibition) as compared to volunteers without the ll-genotype. CONCLUSION: Distinct neuromodulatory effects after intake of citalopram based on allelic variations of the 5-HTTLPR may explain variable response of patients treated with SSRIs.
Authors: B G Pollock; R E Ferrell; B H Mulsant; S Mazumdar; M Miller; R A Sweet; S Davis; M A Kirshner; P R Houck; J A Stack; C F Reynolds; D J Kupfer Journal: Neuropsychopharmacology Date: 2000-11 Impact factor: 7.853
Authors: Bryan Maloney; Balmiki Ray; Elizabeth P Hayden; John I Nurnberger; Debomoy K Lahiri Journal: Psychiatr Genet Date: 2009-04 Impact factor: 2.458
Authors: Charlotte Brasch-Andersen; Malik U Møller; Lene Christiansen; Mikael Thinggaard; Marit Otto; Kim Brøsen; Søren H Sindrup Journal: Eur J Clin Pharmacol Date: 2011-05-26 Impact factor: 2.953