People with medically unexplained symptoms (MUS) often have a comorbid history of stress and negative affect. Although the verbal-cognitive and (peripheral) physiological stress systems have shown a great degree of independence, at the same time it is claimed that chronic stress and negative affect can result in a disregulated physiological stress system, which may lead to MUS. Previous studies could not demonstrate a straightforward between subject relationship between MUS and stress physiology, supporting the view of independence. The aim of the current study was to further explore this relationship using an improved methodology based on ecologically valid 24-h real-life ambulatory recordings. Seventy-four participants (19 male; 55 female) with heterogeneous MUS were compared with 71 healthy controls (26 male; 45 females). Momentary experienced somatic complaints and mood, heart rate, cardiac autonomic activity, respiration and saliva cortisol were monitored using electronic diary and ambulatory registration devices. Participants with MUS reported much more momentary complaints and negative affect as compared to controls. Although MUS seemed to be associated with elevated heart rate and reduced low and very-low frequency heart period variability, these effects disappeared after controlling for differences in sports behaviour. No group differences were found for cardiac autonomic activity, respiration, end-tidal CO2 and saliva cortisol. Our 24-h real-life ambulatory study did not support the existence of a connection between MUS and disregulated peripheral stress physiology. Future studies may instead focus on central measures to reveal potential abnormalities such as deviant central processing of visceral signals in MUS patients.

The predictive value for spontaneous improvement in individuals suffering from medically unexplained symptoms (MUS) was explored of (1) anxiety and depression obtained from questionnaires, (2) negative affective states obtained from experience-sampling, and (3) ambulatory-assessed real-life physiological recordings. Sixty-seven individuals with MUS and 61 healthy controls were included. Twenty-four hour ambulatory recordings of cardiac autonomic activity, respiration, end-tidal CO2 and saliva cortisol were combined with experience-sampling of somatic complaints and mood. Complaints were assessed again after one year. Although a reduction in symptoms (25%) was found, this could not be predicted from initial anxiety and depression. Improvement was somewhat related to relatively low diary reports of fatigue, especially in the late-afternoon and evening (3% variance explained). From the physiological measures only relatively high PetCO2 values in the morning predicted improvement (5% explained). It was concluded that spontaneous recovery from MUS is hard to predict from self-reported distress and ambulatory physiological recordings.

A non-clinical group high on heterogeneous medically unexplained symptoms (MUS; n=97) was compared with healthy controls (n=66) on the within-subject relationships between physiological measures using multilevel path analysis. Momentary experienced somatic complaints, mood (tension and depression), cardiac autonomic activity (inter-beat intervals, pre-ejection period (PEP), and respiratory sinus arrhythmia (RSA)) and respiration (rate and partial pressure of CO2 at the end of a normal expiration) were monitored for 24 h using electronic diary and ambulatory devices. Relationships between measures were controlled for diurnal variation and individual means. Only subtle group differences were found in the diurnal rhythm and in the within-subject relationships between physiological measures. For participants high on MUS, within-subject changes in bodily symptoms were related to changes in mood, but only marginally to the physiological measures. Results of the current path analysis confirm the subordinate role of cardiac autonomic and respiratory parameters in MUS.