Brief ReportsDepleting Serotonin Enhances Both Cardiovascular and Psychological Stress Reactivity in Recovered Patients With Anxiety DisordersDavies, Simon J.C. DM*; Hood, Sean D. MBBS*†; Argyropoulos, Spilios V. PhD*; Morris, Kelly MBBChir*; Bell, Caroline MD*; Witchel, Harry J. PhD‡; Jackson, Peter R. PhD§; Nutt, David J. DM*; Potokar, John P. MD*Author Information *Psychopharmacology Unit, University of Bristol, United Kingdom; †School of Psychiatry and Clinical Neurosciences (M521), University of Western Australia; ‡Department of Physiology, University of Bristol, United Kingdom and §Clinical Pharmacology, Royal Hallamshire Hospital, Sheffield, United Kingdom. Received November 10, 2005; accepted after revision May 4, 2006. Address correspondence and reprint requests to Dr. Simon J.C. Davies, DM, Psychopharmacology Unit, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 8NY, United Kingdom. E-mail: [email protected]. Journal of Clinical Psychopharmacology: August 2006 - Volume 26 - Issue 4 - p 414-418 doi: 10.1097/01.jcp.0000227704.79740.c0 Buy Metrics 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. © 2006 Lippincott Williams & Wilkins, Inc.