title: The 5-HTTLPR genotype modulates heart rate variability and its adjustment by pharmacological panic challenge in healthy men.
abstract: Abnormal serotonin transporter (5-HTT) function and autonomic nervous system (ANS) dysregulation has been proposed in panic disorder. However, in contrast to hypothalamo-pituitary-adrenocortical (HPA) functioning, ANS reactivity during panic response has yet not been investigated in humans with respect to the 5-HTT genotype. The present study assessed the influence of challenging by cholecystokinin tetrapeptide (CCK-4) on heart rate variability (HRV) measures, to monitor autonomic reactivity and its relationship to 5-HTT-linked polymorphic region (5-HTTLPR) genotypes. We hypothesized substantial effects of the 5-HTTLPR genotype on autonomic reactivity. We studied 30 healthy young men, 15 of each with the long/long (l/l) or short/short (s/s) genotype for the 5-HTTLPR. All participants received an intravenous application of 50 μg CCK-4. HRV measures were assessed in both groups at baseline and immediately after CCK-4 application. Our results indicated lower parasympathetic activity in s/s carriers during baseline, time and frequency domain measures. CCK-4 application significantly enhanced the sympathetic tone in both groups, leading to diminished group differences. A significant treatment by genotype effect indicated reduced autonomic reactivity to CCK-4 challenge in the s/s compared to l/l carriers. Our findings show enhanced sympathetic and/or diminished cardiac vagal activity under basal conditions and blunted autonomic reactivity in s/s vs. l/l carriers. Our study provides novel data supporting claims that the s/s genotype represents a genetic vulnerability factor associated with inadequate hyporeactivity to stress and extends current knowledge on the impact of the central serotonergic activity on the sympathoadrenal pathway.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany. Electronic address: aagorast@uke.uni-hamburg.de.
authors.forename: Agorastos
authors.initials: A
authors.lastname: Agorastos
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, Netherlands.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stiedl
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany; Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Muhtz
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany.
authors.forename: Jos S
authors.initials: JS
authors.lastname: Becktepe
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Martini Str. 52, D-20246 Hamburg, Germany.
authors.forename: Cüneyt
authors.initials: C
authors.lastname: Demiralay
mesh_terms: D000704:Analysis of Variance; D001337:Autonomic Agents / Q000494:pharmacology*; D004562:Electrocardiography; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D010200:Panic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013758:Tetragastrin / Q000494:pharmacology*
chemical_list: D001337:Autonomic Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D013758:Tetragastrin
keywords: 5-HTTLPR (serotonin-transporter-linked polymorphic region); Autonomic nervous system; Cholecystokinin tetrapetide (CCK-4); Heart rate variability; Panic; Parasympathetic nervous system; Stress; Sympathetic nervous system