title: Blunted autonomic reactivity to pharmacological panic challenge under long-term escitalopram treatment in healthy men.
abstract: BACKGROUND
  Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV).
  
  
  METHODS
  The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application.
  
  
  RESULTS
  Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; pη(2) = 0.499), SDNN (p < 0.001; pη(2) = 576), RMSSD (p = 0.015; pη(2) = 194), NN50% (p = 0.008; pη(2) = 0.224), and LF% (p = 0.014; pη(2) = 0.196), and moderate effects with respect HF% (p = 0.099; pη(2) = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response.
  
  
  CONCLUSIONS
  Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz). 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, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz).
authors.forename: Michael
authors.initials: M
authors.lastname: Kellner
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz).
authors.forename: Oliver
authors.initials: O
authors.lastname: Stiedl
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz).
authors.forename: Christoph
authors.initials: C
authors.lastname: Muhtz
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz).
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz).
authors.forename: Cüneyt
authors.initials: C
authors.lastname: Demiralay
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005768:Gastrointestinal Hormones / Q000008:administration & dosage / Q000494:pharmacology; D064368:Healthy Volunteers; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D011897:Random Allocation; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013758:Tetragastrin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015283:Citalopram; D005768:Gastrointestinal Hormones; D017367:Selective Serotonin Reuptake Inhibitors; D013758:Tetragastrin
keywords: 5-HTTLPR; CCK-4; SSRI; autonomic nervous system; cholecystokinin tetrapetide; escitalopram; heart rate variability; panic; serotonin-transporter-linked polymorphic region