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

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. Our study aimed to measure neuromodulatory effects of SSRIs on cortical excitability in healthy volunteers characterized by distinct genotypes of the 5-HTTLPR. Cortical excitability was determined in eight genetically defined subjects pre- and post-ingestion of 60 mg citalopram. 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. Distinct neuromodulatory effects after intake of citalopram based on allelic variations of the 5-HTTLPR may explain variable response of patients treated with SSRIs.