Acute tryptophan depletion and stress exposure in patients with panic disorder and healthy controls: effects on heart rate variability

Low heart rate variability (HRV), a risk factor for cardiac disease, was found in patients with panic disorder and might be related to reduced serotonin function and inadequate stress response. This study investigated the effects of experimental lowering of serotonin by acute tryptophan depletion (ATD) on HRV after stress exposure. In a double-blind placebo-controlled cross-over design with ATD vs. placebo, 17 patients with acute or remitted panic disorder (ICD-10, medication-free, no depression, 7 males) and 34 healthy controls (10 males) were compared. As panicogenic stress 35% CO₂ inhalation was induced after 5 hours resting. HRV parameters (standard deviation of successive inter-beat-intervals [IBI-SD], root mean square of successive inter-beat-interval differences [RMSSD]) were recorded and analyzed in artifact-free successive 20-s intervals and were compared between patients and controls during resting and following CO₂-inhalation after ATD vs. placebo with repeated measurement ANOVA. Age (patients 38+/-14y, controls 33+/-12y), socio-demographic data and smoking status (41% vs. 29%) were comparable. During resting neither in patients nor in controls HRV did change significantly after ATD or placebo (P>0.20). After CO₂ inhalation, HRV decreased significantly in patients and controls following ATD (ATD vs. placebo IBI-SD, P=0.012; RMSSD, P=0.036) with a significantly more pronounced decrease in patients with panic disorder (interaction IBI-SD P=0.016; RMSSD P=0.046).