title: Allelic variation in the serotonin transporter promoter affects neuromodulatory effects of a selective serotonin transporter reuptake inhibitor (SSRI).
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Psychiatry and Psychotherapy, University of Regensburg, Universitaetsstrasse 84, 93053, Regensburg, Germany. peter.eichhammer@bzk.uni-regensburg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Eichhammer
authors.forename: Berthold
authors.initials: B
authors.lastname: Langguth
authors.forename: Rainer
authors.initials: R
authors.lastname: Wiegand
authors.forename: Alexander
authors.initials: A
authors.lastname: Kharraz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frick
authors.forename: Göran
authors.initials: G
authors.lastname: Hajak
mesh_terms: D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D015283:Citalopram / Q000097:blood / Q000494:pharmacology; D004594:Electrophysiology; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D009044:Motor Cortex / Q000033:anatomy & histology / Q000187:drug effects; D009419:Nerve Tissue Proteins; D009420:Nervous System / Q000187:drug effects*; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D015283:Citalopram; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human