The role of serotonin for gastrointestinal symptoms: Acute tryptophan depletion increases nausea

Acute tryptophan depletion (ATD) is an experimental model to reduce central serotonin levels. It has been shown to induce gastrointestinal symptoms in IBS patients. We wondered whether ATD can induced nausea in healthy subjects during motion.

Methods: 38 healthy female subjects were screened for motion sickness susceptibility (MSSQ) and randomly assigned to two groups (ATD and placebo) in a double blinded design. They received either a protein drink without tryptophan (but substituted by other amino acids) (ATD condition) or a balanced protein drink tryptophan (placebo condition). Four hours after its consumption they were exposed to a standard rotation procedure (5×1min with 1 to 2min breaks). Symptom ratings (SR) were taken on a 7 item VAS scale prior to rotation, at each break, and 15 and 30min thereafter. Saliva samples were collected to assess the cortisol levels in the morning upon arrival in the laboratory, and immediately prior to and immediately after rotation, and 15 and 30min later. Data were compared between conditions (ATD, control) by ANOVA with psychometric (SR) and biological variables (cortisol) as dependent variables, and MSSQ and menstrual cycle phase as covariates.

Results: Four subjects could not tolerate the entire rotation procedure and were excluded from analysis. For the remaining 34, SR was significantly higher during ATD than during control conditions (p=0.025). Cortisol levels rose significantly with rotation (p<0.001) but were unaffected by ATD. The MSSQ score and the maximum SR during rotation were significantly associated (r=.465, p=0.006), as were maximal SR and cortisol increase with rotation (r=.443, p=0.011). High morning cortisol as well as baseline cortisol levels, however were associated with lower ratings during rotation (r=-.335; p=0.040 and r=-.376;p=0.022 resp.). The protective effects of high morning cortisol were pronounced during the menstrual and follicular phase of the cycle (r=-,616, p=0.025) and not present during ovulation and the luteal phase.

Conclusion: Reducing central serotonin does enforce nausea in healthy female subjects when exposed to rotation. However, nausea is as well affected by the acute cortisol levels and the menstrual cycle in a rather complex fashion.