Allelic variation in the serotonin transporter promoter affects neuromodulatory effects of a selective serotonin transporter reuptake inhibitor (SSRI)

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 (1) and short (s). Homozygosity for the long variant (11-genotype) is associated with a two times more efficient 5-HT uptake compared to the s/l- or s/sgenotype. 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 11-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 11-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.