title: Depleting serotonin enhances both cardiovascular and psychological stress reactivity in recovered patients with anxiety disorders.
abstract: Serotonin-promoting drugs show cardioprotective properties in patients with anxiety or depression, but it is not known if this is a direct effect of increasing serotonin. We aimed to characterize the effect of serotonin manipulation through acute tryptophan depletion on cardiovascular and psychological responses to stress challenge in recovered patients with anxiety disorders. In 27 recovered patients with anxiety disorders (panic disorder treated by selective serotonin reuptake inhibitors (SSRIs) or cognitive behavioral therapy, social anxiety disorder treated by SSRIs), we performed a double-blind randomized crossover study. On 2 separate days, the subjects ingested an acute tryptophan-depleting (aTD) or nondepleting (nD) drink in random order and underwent a stress challenge at time of maximum depletion. Systolic blood pressure (P = 0.007; diff = 9.0 mm Hg; 95% confidence interval (CI), 2.6-15.3 mm Hg) and diastolic blood pressure (P = 0.032; diff = 5.7 mm Hg; 95% CI, 0.6-10.9 mm Hg) responses to stress were significantly greater under aTD than nD, as were the psychological responses to stress (for Spielberger state anxiety, difference in stress response between aTD and nD = 7.11; P = 0.025). Blood pressure responses to stress showed no correlation with psychological responses. The significant increases in acute stress sensitivity in both cardiovascular and psychological domains on serotonin depletion suggest that serotonin is involved in the control of both cardiovascular and psychological aspects of the acute stress response. The lack of correlation in the difference between aTD and nD conditions in cardiovascular and psychological responses suggests that serotonin may have distinct effects on these 2 domains, rather than the cardiovascular responses being merely a secondary consequence of psychological changes.
authors.affiliation: Psychopharmacology Unit, University of Bristol, Whitson Street, Bristol BS1 8NY, United Kingdom. Simon.Davies@bristol.ac.uk
authors.forename: Simon J C
authors.initials: SJ
authors.lastname: Davies
authors.forename: Sean D
authors.initials: SD
authors.lastname: Hood
authors.forename: Spilios V
authors.initials: SV
authors.lastname: Argyropoulos
authors.forename: Kelly
authors.initials: K
authors.lastname: Morris
authors.forename: Caroline
authors.initials: C
authors.lastname: Bell
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Witchel
authors.forename: Peter R
authors.initials: PR
authors.lastname: Jackson
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: John P
authors.initials: JP
authors.lastname: Potokar
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000150:complications / Q000188:drug therapy; D020127:Recovery of Function / Q000187:drug effects; D012701:Serotonin / Q000172:deficiency* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013315:Stress, Psychological / Q000503:physiopathology*; D014364:Tryptophan / Q000097:blood / Q000172:deficiency
chemical_list: D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan