Preliminary evidence on the direction of effects between day-to-day changes in cellular immune activation, fatigue and mood in a patient with prior breast cancer: A time-series analysis approach

This study on a patient with prior breast cancer investigated the cause-effect relations between immune system activation, fatigue and mood under real-life conditions. The 60-year old woman (primary diagnosis 5 years ago, relapse one year ago, currently no signs of recurrence) collected her entire urine for 31 days in 12 hour intervals for the determination of immune activation marker neopterin and creatinine concentrations by HPLC. This study used only the daytime urinary neopterin concentrations (from approx. 8 a. m. to 8 p. m.) and cross-correlated them with daily data from mood (3-Skalen-EWL) and fatigue (VAS) questionnaires which the patient filled in for 31 days. Serial dependencies were controlled for by applying moving average smoothing. When averaged over the whole observation period, daily fatigue, daily mood and daily urinary neopterin (average 173 mu mol per mol creatinine) were within normal limits. Cross-correlational analyses revealed that increases in urinary neopterin significantly preceded increases in fatigue by 24 hours (lag 1: r = +0.424; p < 0.05). The opposite direction of effects, however, existed between mood and neopterin, i.e., decreases in mood preceded increases in neopterin by 96 hours (lag 4: r = -0.697; p < 0.05). The results in this patient suggest a disturbed stress system activity where negative emotions are associated with increases instead of decreases in the degree of cellular immune activation and where cellular immune activation may trigger central nervous system symptoms such as fatigue. Despite some restrictions in data quality this study shows the feasibility of gathering evidence on naturally occurring psychoimmunological cause-effect relations based on extensive serial data collection and time series analysis.