Psychological flexibility in somatic symptom and related disorders: A case control study.

A key diagnostic criterion of Somatic Symptom and related Disorders (SSD) comprises significant distress and excessive time-and-energy consuming thoughts, feelings, and behavior pertaining to somatic symptoms. This diagnostic criterion is lacking in central sensitivity syndromes (CSS), such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome. This strong emphasis on disturbed psychological processing of somatic symptoms, suggests that psychological flexibility is low in SDD. Psychological flexibility is defined as the ability to approach difficult or challenging internal states (thoughts, emotions, and bodily sensations) in a non-judgmental, mindful way, and being committed to pursue one's values. To clarify the potential significance of psychological flexibility in SSD, we examined its levels in 154 people referred to specialized treatment for SDD, as compared to reference groups from the general population encompassing 597 people with CSS and 1422 people without SSD or CSS (controls). Mean levels of psychological flexibility (adjusted for demographic covariates) were lowest for SSD and highest for controls (F = 154.5, p < 0.001, pη2 = 0.13). Percentages of people with low psychological flexibility (<0.8 SD below the mean of controls) were: SSD 74%, CSS 42%, controls 21%. In SSD, higher psychological flexibility was associated with better mental health (ß = 0.56, p < 0.001), but interaction analysis rejected that psychological flexibility preserved health when having more severe somatic symptoms (ß ≤ 0.08, p ≥ 0.10). The results indicate that lower psychological flexibility is a prevalent problem in SSD that is associated with lower mental health. This suggests that it is worthwhile to take account of psychological flexibility in SSD in screening, monitoring, and therapy.

Changed dynamic symptom networks after a self-compassion training in patients with somatic symptom disorder: A multiple single-case pilot project.

OBJECTIVE: Pre-to-post mean group differences of intermittently assessed generic outcome variables may not capture all relevant treatment-related changes in individual patients with somatic symptom disorder (SSD). Aim of this multiple single-case observational pilot project was to find out whether the Experience Sampling Method (ESM) and dynamic symptom networks may offer new opportunities in evaluating treatment outcomes for individual patients with SSD. METHODS: Patients with SSD (N = 6 in study 1, N = 7 in study 2) received a self-compassion training in a tertiary care mental health expert center. Using a single-case pre-post treatment observational design, intensive longitudinal data were collected with ESM. A brief questionnaire was presented via the patient's smartphone three times per day for 16 weeks before, during and after the training in study 1, and for 5 weeks before and 5 weeks after the training in study 2. Eleven questions comprised somatic symptoms, functional disability, stress, self-compassion, and acceptance of affect; three personalized questions comprised self-chosen affects and an additional symptom. RESULTS: Sufficient observations for means and network comparison were obtained for 11 and 10 patients, respectively. After the training, self-compassion was significantly increased in 10 patients, functional disability, stress and affect improved in 6 patients, and (although not a treatment goal) somatic symptoms decreased in 6 patients. Dynamic symptom networks significantly changed in 5 patients. CONCLUSION: Patient-specific changes in means and dynamic symptom networks were observed after self-compassion training. In future clinical trials, single-case ESM may offer new opportunities to evaluate treatment outcomes in patients with SSD.

Ecological momentary assessment study of exposure to radiofrequency electromagnetic fields and non-specific physical symptoms with self-declared electrosensitives.

The main objective of the study is to determine if non-specific physical symptoms (NSPS) in people with self-declared sensitivity to radiofrequency electromagnetic fields (RF EMF) can be explained (across subjects) by exposure to RF EMF. Furthermore, we pioneered whether analysis at the individual level or at the group level may lead to different conclusions. By our knowledge, this is the first longitudinal study exploring the data at the individual level. A group of 57 participants was equipped with a measurement set for five consecutive days. The measurement set consisted of a body worn exposimeter measuring the radiofrequency electromagnetic field in twelve frequency bands used for communication, a GPS logger, and an electronic diary giving cues at random intervals within a two to three hour interval. At every cue, a questionnaire on the most important health complaint and nine NSPS had to be filled out. We analysed the (time-lagged) associations between RF-EMF exposure in the included frequency bands and the total number of NSPS and self-rated severity of the most important health complaint. The manifestation of NSPS was studied during two different time lags - 0-1 h, and 1-4 h - after exposure and for different exposure metrics of RF EMF. The exposure was characterised by exposure metrics describing the central tendency and the intermittency of the signal, i.e. the time-weighted average exposure, the time above an exposure level or the rate of change metric. At group level, there was no statistically significant and relevant (fixed effect) association between the measured personal exposure to RF EMF and NSPS. At individual level, after correction for multiple testing and confounding, we found significant within-person associations between WiFi (the self-declared most important source) exposure metrics and the total NSPS score and severity of the most important complaint in one participant. However, it cannot be ruled out that this association is explained by residual confounding due to imperfect control for location or activities. Therefore, the outcomes have to be regarded very prudently. The significant associations were found for the short and the long time lag, but not always concurrently, so both provide complementary information. We also conclude that analyses at the individual level can lead to different findings when compared to an analysis at group level.

A concept mapping study on perpetuating factors of functional somatic symptoms from clinicians' perspective.

OBJECTIVE: The aim of this concept mapping study was to identify the structure and alleged importance of perpetuating factors of functional somatic symptoms (FSS) from the perspective of professionals. Further, we examined to which extent these factors have been addressed in scientific literature. METHODS: Ninety-nine perpetuating factors were sorted with respect to content using a card-sorting task by 61 experienced clinicians (62.3% psychologists, 75.4% female, mean age: 45.7 [SD: 10.6] years, mean duration of experience in treating FSS patients: 10.5 [SD: 7.6] years). These factors had been derived from in-depth interviews with 12 clinicians, with extensive experience in treating FSS. Thirty-eight clinicians rated the importance of the 99 factors on a scale ranging from 1 ('not important at all') to 10 ('extremely important'). RESULTS: Hierarchical cluster analysis revealed three overarching domains of perpetuating factors: 'Hypochondria', 'Social and relational problems' and 'Symptom-related emotions and habits'. These domains comprised 16 clusters, which were rated on importance between 6.1, 'Adverse physical factors and counterproductive lifestyle', and 7.8, 'Frustration and despair regarding the symptoms'. All clusters have been addressed in scientific literature. CONCLUSIONS: This study revealed an encompassing hierarchical structure of somatic, emotional, cognitive, behavioral, and social factors of importance in the perpetuation of FSS based on expert opinions. This structure will guide the development of personalized treatment of FSS.

Incorporating measurement error in n = 1 psychological autoregressive modeling.

Measurement error is omnipresent in psychological data. However, the vast majority of applications of autoregressive time series analyses in psychology do not take measurement error into account. Disregarding measurement error when it is present in the data results in a bias of the autoregressive parameters. We discuss two models that take measurement error into account: An autoregressive model with a white noise term (AR+WN), and an autoregressive moving average (ARMA) model. In a simulation study we compare the parameter recovery performance of these models, and compare this performance for both a Bayesian and frequentist approach. We find that overall, the AR+WN model performs better. Furthermore, we find that for realistic (i.e., small) sample sizes, psychological research would benefit from a Bayesian approach in fitting these models. Finally, we illustrate the effect of disregarding measurement error in an AR(1) model by means of an empirical application on mood data in women. We find that, depending on the person, approximately 30-50% of the total variance was due to measurement error, and that disregarding this measurement error results in a substantial underestimation of the autoregressive parameters.

The day-to-day concurrence of bodily complaints and affect in patients with severe somatoform disorder.

Based on the concept of somatization, psychological distress can be experienced as symptoms of physical illness. This suggests a close-fitting intra-individual association between bodily complaints and mood in patients with somatoform disorder (SFD). The contemporaneous day-to-day complaints-mood association was investigated in patients with severe chronic SFD using an ecological momentary assessment (EMA) design. Eleven patients, who had recently received specialized tertiary care treatment for severe chronic SFD, kept an online electronic diary for four consecutive weeks. They were prompted at intervals throughout the day to complete questions on their momentary primary symptoms (pain and fatigue), and mood state (negative and positive). For each measure, day-mean aggregated values were computed and analyzed using linear multilevel (mixed model) regression analysis. Fixed factor results showed that symptoms were associated with both negative mood state (ß = 0.47) and positive mood state (ß = -0.59). Random results, however, indicated large inter-individual differences, with correlations varying between 0.17 and 0.99 for negative affect, and between -0.88 and 0.14 for positive affect. A substantial day-to-day contemporaneous association between symptoms and affect across subjects, as well as large inter-individual differences in this association, were demonstrated in patients with severe chronic SFD. EMA-data showing the relationship between both negative and (inverse) positive mood and complaints has potential clinical relevance: providing SFD patients with feedback consisting of their personal day-to-day concurrency graph may promote their understanding of their own complaints in a broader context than the somatic area.

Intensive multidisciplinary treatment of severe somatoform disorder: a prospective evaluation.

Chronic severe somatoform disorder (SFD) is resistant to treatment. In a prospective observational study, we evaluated an intensive multidisciplinary treatment focusing on body-related mentalization and acceptance. Patients included in the study were 183 (146 women, 37 men) of 311 eligible patients with chronic severe SFD, referred consecutively to a specialized tertiary care center between 2002 and 2009. Primary outcome measures were somatic symptoms (SCL-90) and health-related quality of life (EuroQol 5-Dimensional [EQ-5D]). These measures were assessed four times before treatment (on intake, twice during an observation period, at start of treatment) and four times after treatment (during follow-up for 2 years). Multilevel analysis was used to separate effects of time (maturation) and treatment. Results revealed significant improvements in SCL-90 somatic symptoms (d = 0.51), EQ-5D index (d = 0.27), and EQ visual analogue scale (d = 0.56). Significant reductions were also observed in SCL-90 anxiety, depression, and overall psychopathology as well as in medical consumption associated with psychiatric illness (Trimbos/iMTA Questionnaire for Costs Associated With Psychiatric Illness). Large interindividual differences were found in treatment outcome. The long-term improvement seen in many patients suggests that intensive multidisciplinary tertiary care treatment is a useful approach to chronic severe SFD.

Effectiveness of psychotherapy for severe somatoform disorder: meta-analysis.

BACKGROUND: Patients with severe somatoform disorder (in secondary and tertiary care) typically experience functional impairment associated with physical symptoms and mental distress. Although psychotherapy is the preferred treatment, its effectiveness remains to be demonstrated. AIMS: To examine the effectiveness of psychotherapy for severe somatoform disorder in secondary and tertiary care compared with treatment as usual (TAU) but not waiting-list conditions. METHOD: Main inclusion criteria were presence of a somatoform disorder according to established diagnostic criteria and receiving psychotherapy for somatoform disorder in secondary and tertiary care. Both randomised and non-randomised trials were included. The evaluated outcome domains were physical symptoms, psychological symptoms (depression, anxiety, anger, general symptoms) and functional impairment (health, life satisfaction, interpersonal problems, maladaptive cognitions and behaviour). RESULTS: Ten randomised and six non-randomised trials were included, comprising 890 patients receiving psychotherapy and 548 patients receiving TAU. Psychotherapy was more effective than TAU for physical symptoms (d = 0.80 v. d = 0.31, P<0.05) and functional impairment (d = 0.45 v. d = 0.15, P<0.01), but not for psychological symptoms (d = 0.75 v. d = 0.51, P = 0.21). These effects were maintained at follow-up. CONCLUSIONS: Overall findings suggest that psychotherapy is effective in severe somatoform disorder. Future randomised controlled studies should examine specific interventions and mechanisms of change.

The impact of emotion-related autonomic nervous system responsiveness on pain sensitivity in female patients with fibromyalgia.

OBJECTIVE: Patients with fibromyalgia have shown hyporeactive autonomic nervous system (ANS) responses to physical stressors, augmented pain to ANS changes, and heightened negative emotions, which can increase pain. This study examined ANS reactivity to negative emotions and its association with pain in fibromyalgia and control participants. METHODS: Sixty-two women with fibromyalgia and 59 women in a control group recalled neutral, and anger- and sadness-eliciting experiences while ANS activity was monitored. Clinical and experimental pain were assessed in response to each emotion. RESULTS: Compared with neutral recall, heart rate (p = .050), mean arterial pressure (p < .001), and high-frequency heart rate variability (p = .012) increased in response to sadness, whereas heart rate decreased (p = .002) and mean arterial pressure increased (p < .001) in response to anger; however, ANS responses did not differ between patients and control participants (all p > .29). Among patients only, decreased preejection period (anger-pain threshold: r = 0.31, p = .018) and total peripheral resistance in response to negative emotions (anger-pain tolerance: r = 0.35, p = .025; sadness-pain threshold: r = 0.51, p < .001; sadness-pain tolerance: r = 0.61, p < .001) correlated with more pain. CONCLUSIONS: These data suggest that the ANS is not hyporesponsive to elicited emotions in fibromyalgia; however, patients with a larger pain response showed an ANS response pattern reflecting heightened ß-adrenergic and reduced α-adrenergic reactivity. Future research should test whether a specific ANS response pattern to emotions is a consequence of increased pain or whether it amplifies pain.

Prodromal functioning of migraine patients relative to their interictal state--an ecological momentary assessment study.

Smartphones were used in an online Ecological Momentary Assessment (EMA) design to test prodromal functioning relative to the interictal state in migraine patients. Eighty-seven participants completed an electronic diary 4 times daily during 3-6 weeks to monitor their migraine attacks. Twice daily the diary additionally included 16 multi-answer questions covering physical symptoms (30 items), cognitive-affective functioning (25 items) and external factors (25 items). Eight clustered prodromal features were identified in the current study: sensory sensitivity, pain/stiffness, fatigue, cognitive functioning, positive affect, negative affect, effort spent and stressors encountered. Per feature, individual change scores with interictal control days--excluding 24-hour post-attack recovery--were computed for six 12-hour pre-attack time windows covering three prodromal days. Linear mixed model (fixed-effect) analysis established significant increases in sensory sensitivity, pain/stiffness and fatigue, and a tendency for increased negative affect, in the 12 hours prior to the attack. Positive affect and cognitive functioning were impaired both in the 25-36 hour and--more strongly--in the 12-hour time window before the attack. No effects were found for effort spent and stressors encountered. Exploratory (random effect) analysis revealed significant individual differences in the change scores in sensory sensitivity, pain/stiffness, fatigue and negative affect. It is concluded that the prodromal change in migraine--relative to interictal functioning--predominantly exists within the last 12 hours before attack onset. Individual diversity is large, however. Future research should zoom in to identify prodrome development within the 12 pre-attack hours as well as to isolate individual patterns.

Infection load as a predisposing factor for somatoform disorders: evidence from a Dutch General Practice Registry.

OBJECTIVE: Somatoform disorders (SDs) are characterized by chronic multiple functional somatic (FS) symptoms. It has been suggested that infections may be triggers for FS symptoms to occur, pointing to the immune system as a pathogenic factor in their development. The current study aimed to compare the prevalence of infections (i.e., infection load) in the history of patients with SDs with that of matched controls. METHODS: Samples (n = 185) were identified in the Psychiatric Case Register Middle Netherlands and the Julius General Practitioners Network. Patients with an SD diagnosis in the Psychiatric Case Register Middle Netherlands were compared with matched persons without somatoform complaints (controls) on their infection load in two periods before the date of the psychiatric diagnosis or a matched date for the controls (i.e., the total period for which data were available and a 3-year period). Infection load was defined as the total number of infections documented in the Julius General Practitioners Network. RESULTS: Patients with SD had significantly more infections than did controls in both periods (total period: mean [standard error] = 0.87 [0.10] versus 0.51 [0.06], z = -3.08, p = .002; 3-year period: 3.44 [0.47] versus 2.15 [0.50], z = -2.91, p = .004). CONCLUSIONS: Results show that patients with SD have a higher infection load preceding their diagnosis as compared with matched controls, implicating that infection load may indeed predispose for developing FS symptoms. These findings emphasize the importance of further research on immunological mechanisms in FS symptoms. Limitations of the study are discussed.

Design of an ecological momentary assessment study of exposure to radiofrequency electromagnetic fields and non-specific physical symptoms.

INTRODUCTION: Idiopathic Environmental Intolerance (IEI) attributed to electromagnetic fields (EMF) refers to self-reported sensitivity mainly characterised by the attribution of non-specific physical symptoms to low-level EMF exposure emitted from sources such as mobile phones. Scientific studies have not provided evidence for the existence of IEI-EMF, but these studies did not resemble the real-life situation or suffered from poor exposure characterisation and biased recall of health symptoms. To improve existing methods for the study of IEI-EMF, an Ecological Momentary Assessment (EMA) study is designed. METHODS AND ANALYSIS: The study is an EMA study in which respondents carry personal exposure metres (exposimeters) that measure radiofrequency (RF) EMF, with frequent assessment of health symptoms and perceived EMF exposure through electronic diary registration during five consecutive days. Participants will be a selection from an epidemiological study who report to be sensitive to RF EMF. The exposimeters measure electric field strength in 12 frequency bands. Diary questions include the occurrence and severity of 10 non-specific physical symptoms, mood states and perceived exposure to (sources of) EMF. The relationship of actual and perceived EMF exposure and mood with non-specific physical symptoms will be analysed using multilevel regression analysis with time-shift models. DISCUSSION: The study has several advantages over previous studies, including assessment of personal EMF exposure and non-specific physical symptoms by an ecological method with a minimised chance of recall bias. The within-person design reduces confounding by time-stable factors (eg, personal characteristics). In the conduct of the study and the analysis and interpretation of its outcomes, some methodological issues including a high participant burden, reactivity, compliance to the study protocol and the potential of chance findings due to multiple statistical testing will be accounted for and limited as much as possible.

Experimental pressure-pain assessments: Test-retest reliability, convergence and dimensionality.

Introduction Experimental pain studies can provide unique insight into the dimensions of pain and into individual differences in pain responsiveness by controlling different aspects of pain-eliciting stimuli and pain measures. In experimental pain studies, pain responsiveness can be assessed as pain threshold, pain tolerance or pain ratings. The test-theoretical qualities of these different measures, however, have not yet been completely documented. In the current study, several of these qualities were investigated in a pain experiment applying different algometric techniques. The objective of the study was to investigate the reliability (test-retest) and the convergent validity (correspondence) of the different methods found in the literature of measuring pressure-pain threshold, and the interrelationship between pressure-pain threshold, pressure-pain tolerance, and pressure-pain ratings. Methods Sixty-six healthy female subjects were enrolled in the study. All pressure stimuli were applied by a trained investigator, using a digital algometer with a 1 cm2 rubber tip. Pressure-pain thresholds were assessed repeatedly on six different body points (i.e. left and right calf one third of total calf muscle length below the popliteal space), the lower back (5 cm left and right from the L3), and left and right forearm (thickest part of brachioradialis muscle). Next, pressure-pain tolerance was measured on the thumbnail of the non-dominant hand, followed by rating affective and sensory components (on visual analogue scales) of a stimulus at tolerance level. Last, affective and sensory ratings were obtained for two pressure intensities. Results With intraclass correlations above .75 for pain responses per body point, test-retest reliability was found to be good. However, values obtained from all first measurements were significantly higher as compared with the two succeeding ones. Convergent validity of pain thresholds across different body points was found to be high for all combinations assessed (Cronbach's alpha values >.80), but the highest for bilateral similar body parts (>.89). Finally, principal components analysis including measures of threshold, tolerance and pain ratings yielded a three-factor solution that explained 81.9% of the variance: Moderate-level stimulus appraisal & pain tolerance; Pain threshold; Tolerance-level stimulus appraisal. Conclusion and implications Findings of the current study were used to formulate recommendations for future algometric pain studies. Concerning pressure-pain threshold, it is recommended to exclude first measurements for every body point from further analyses, as these measurements were found to be consistently higher compared with the following measurements. Further, no more than two consecutive measurements (after the first measurement) are needed for a reliable mean threshold value per body point. When combining threshold values of several body points into one mean-aggregated threshold value, we suggest to combine bilateral similar points, as convergent validity values were highest for these combinations. The three-factor solution that was found with principal components analyses indicates that pressure-pain threshold, subjective ratings of moderate intensity stimuli, and subjective ratings of the maximum (tolerance) intensity are distinct aspects of pain responsiveness. It is therefore recommended to include a measure of each of these three dimensions of pain when assessing pressure pain responsiveness. Some limitations of our study are discussed.

Using multilevel path analysis in analyzing 24-h ambulatory physiological recordings applied to medically unexplained symptoms.

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 CO(2) 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.

Comparing low frequency heart rate variability and preejection period: two sides of a different coin.

It has been hypothesized that the ratio of heart rate variability in the low- (LF) and high- (HF) frequency bands may capture variation in cardiac sympathetic control. Here we tested the temporal stability of the LF/HF ratio in 24-h ambulatory recordings and compared this ratio to the preejection period (PEP), an established measure of cardiac sympathetic control. Good temporal stability was found across a period of 3.3 years (.46

Negative affect and 24-hour ambulatory physiological recordings as predictors of spontaneous improvement of medically unexplained symptoms.

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 CO(2) 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 PetCO(2) 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.

Medically unexplained symptoms and between-group differences in 24-h ambulatory recording of stress physiology.

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 CO(2) 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.

Heterogeneous medically unexplained symptoms and immune function.

It has been suggested that dysregulation of immune-to-brain communication plays a role in the biopsychological process underlying medically unexplained symptoms (MUS). Immune and non-immune stressors can both be involved in the activation of the central sickness-behavioural-system leading to complaints like malaise, pain and fatigue. We hypothesized increased pro-inflammatory and/or reduced anti-inflammatory cytokine activity to exist in MUS patients. Twenty-seven participants (4 male; 23 female) with heterogeneous MUS were compared with 27 healthy controls (6 male; 21 females). Blood samples were analysed for leukocyte subset cell counts, in vitro T-cell mitogen-stimulated cytokine production (IL-2, IL-4, IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) and in vitro monocyte cytokine release (IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha) in response to increasing concentrations of LPS. No significant group differences were found for any of the cytokines measured. One unexpected exception was an elevation in the number of circulating B and NK-cells in participants high on MUS. Nonetheless, no support was found for the hypothesized immunological dysregulation in peripheral blood leukocyte function of MUS patients.

Comparison of time and frequency domain measures of RSA in ambulatory recordings.

The extent to which various measures of ambulatory respiratory sinus arrhythmia (RSA) capture the same information across conditions in different subjects remains unclear. In this study the root mean square of successive differences (RMSSD), peak valley RSA (pvRSA), and high frequency power (HF power) were assessed during ambulatory recording in 84 subjects, of which 64 were retested after about 3 years. We used covariance structure modeling to test the equality of the correlations among three RSA measures over two test days and three conditions (daytime sitting or walking and nighttime sleep) and in groups with low, medium, and high mean heart rate (HR), or low, medium, and high mean respiration rate (RR). Results showed that ambulatory RMSSD, pvRSA, and HF power are highly correlated and that their correlation is stable across time, ambulatory conditions, and a wide range of resting HR and RR values. RMSSD appears to be the most cost-efficient measure of RSA.