Predictors of symptom trajectory in newly diagnosed ulcerative colitis: a 3-year follow-up cohort study.

BACKGROUND AND AIMS: Psychological symptoms are associated with poorer ulcerative colitis (UC)-related outcomes. However, the majority of research is cross-sectional. We aimed to identify subgroups based on the longitudinal evolution of GI symptom levels and health-related quality of life (HRQoL), and to disentangle the directionality of effects between GI symptom levels and psychological distress. METHODS: Self-reported GI symptom severity, HRQoL, inflammatory biomarkers and psychological distress were assessed in 98 newly diagnosed UC patients at disease onset and yearly for 3 consecutive years. Latent class growth analysis was used to determine subgroups based on longitudinal trajectories of symptom severity and HRQoL, and baseline predictors of trajectory group membership were determined. Cross-lagged structural equation models were used to disentangle temporal relationships between psychological functioning and symptom severity. RESULTS: Patients with higher initial psychological distress had increased probability of maintaining higher levels of diarrhea and abdominal pain. Conversely, patients with lower initial levels of diarrhea and abdominal pain had higher chances of maintaining lower levels of psychological distress. Higher levels of C-reactive protein at baseline predicted greater improvements in mental health after anti-inflammatory treatment. Reductions in diarrhea and abdominal pain preceded reductions in psychological symptoms over time. CONCLUSIONS: Baseline psychological distress is predictive of increased GI symptom severity and reduced mental HRQoL over time, suggesting early assessment of psychological symptoms may identify patients who may have worse disease trajectories. Abdominal pain predicted increased psychological distress, but not the other way around. Intervening on abdominal pain may help prevent or reduce future psychological distress.

Poor Subjective Sleep Quality Predicts Symptoms in Irritable Bowel Syndrome Using the Experience Sampling Method.

INTRODUCTION: Sleep quality may affect symptom experience in irritable bowel syndrome (IBS). Our aim was to investigate the relationship between sleep quality and gastrointestinal (GI) symptoms using actigraphy and the experience sampling method. METHODS: Patients with IBS were recruited from a tertiary Neurogastroenterology clinic and the community. GI symptoms and mood were recorded on a smartphone application, 10 times per day, over 7 consecutive days. Subjective sleep quality was recorded every morning to reflect the night before. Objective measures of sleep quality were estimated from wrist-worn actigraphy. Cross-lagged structural equation models were built to assess the directionality of sleep-symptom relationships over time. RESULTS: Eighty patients with IBS completed the study (mean age: 37 years [range 20-68], 89% female, 78% community). Approximately 66% had a Pittsburgh Sleep Quality Index score ≥ 8, indicating a clinically significant sleep disturbance. Approximately 82% (95% CI: 72-90) screened positive for a sleep disorder, most commonly insomnia. In cross-lagged analysis, poor subjective sleep quality predicted next-day abdominal pain (0.036 < P < 0.040) and lower GI symptoms (0.030 < P < 0.032), but not vice versa. No significant relationship with GI symptoms was found for any objective sleep measure using actigraphy. DISCUSSION: Poor subjective sleep quality was associated with higher next-day lower GI symptom levels, but not vice versa. Objective sleep measures did not predict next-day abdominal symptoms, potentially supporting the conclusion that it is the perception of sleep quality that is most influential. This study may be used to guide future research into the effect of sleep interventions on GI symptoms.

Brain mediators of negative affect-induced physical symptom reporting in patients with functional somatic syndromes.

Functional somatic syndromes (FSS) include fibromyalgia, irritable bowel syndrome (IBS), and others. In FSS patients, merely viewing negative affective pictures can elicit increased physical symptoms. Our aim was to investigate the neural mechanisms underlying such negative affect-induced physical symptoms in FSS patients. Thirty patients with fibromyalgia and/or IBS and 30 healthy controls (all women) watched neutral, positive and negative affective picture blocks during functional MRI scanning and rated negative affect and physical symptoms after every block. We compared brain-wide activation during negative versus neutral picture viewing in FSS patients versus controls using robust general linear model analysis. Further, we compared neurologic pain signature (NPS), stimulus intensity-independent pain signature (SIIPS) and picture-induced negative emotion signature (PINES) responses to the negative versus neutral affect contrast and investigated whether they mediated between-group differences in affective picture-induced physical symptom reporting. More physical symptoms were reported after viewing negative compared to neutral pictures, and this effect was larger in patients than controls (p = 0.025). Accordingly, patients showed stronger activation in somatosensory regions during negative versus neutral picture viewing. NPS, but not SIIPS nor PINES, responses were higher in patients than controls during negative versus neutral pictures (p = 0.026). These differential NPS responses partially mediated between-group differences in physical symptoms. In conclusion, picture-induced negative affect elicits physical symptoms in FSS patients as a result of activation of somatosensory and nociceptive brain patterns, supporting the idea that affect-driven alterations in processing of somatic signals is a critical mechanism underlying FSS.

Clinical phenotypes and prognostic factors in persons with hip osteoarthritis undergoing total hip arthroplasty: protocol for a longitudinal prospective cohort study (HIPPROCLIPS).

BACKGROUND: Large heterogeneity exists in the clinical manifestation of hip osteoarthritis (OA). It is therefore not surprising that pain and disability in individuals with hip OA and after total hip arthroplasty (THA) cannot be explained by biomedical variables alone. Indeed, also maladaptive pain-related cognitions and emotions can contribute to pain and disability, and can lead to poor treatment outcomes. Traumatic experiences, mental disorders, self-efficacy and social support can influence stress appraisal and strategies to cope with pain, but their influence on pain and disability has not yet been established in individuals with hip OA undergoing THA. This study aims (1) to determine the influence of traumatic experiences and mental disorders on pain processing before and shortly after THA (2) to identify preoperative clinical phenotypes in individuals with hip OA eligible for THA, (3) to identify pre- and early postoperative prognostic factors for outcomes in pain and disability after THA, and (4) to identify postoperative clinical phenotypes in individuals after THA. METHODS: This prospective longitudinal cohort study will investigate 200 individuals undergoing THA for hip OA. Phenotyping variables and candidate prognostic factors include pain-related fear-avoidance behaviour, perceived injustice, mental disorders, traumatic experiences, self-efficacy, and social support. Peripheral and central pain mechanisms will be assessed with thermal quantitative sensory testing. The primary outcome measure is the hip disability and osteoarthritis outcome score. Other outcome measures include performance-based measures, hip muscle strength, the patient-specific functional scale, pain intensity, global perceived effect, and outcome satisfaction. All these measurements will be performed before surgery, as well as 6 weeks, 3 months, and 12 months after surgery. Pain-related cognitions and emotions will additionally be assessed in the early postoperative phase, on the first, third, fifth, and seventh day after THA. Main statistical methods that will be used to answer the respective research questions include: LASSO regression, decision tree learning, gradient boosting algorithms, and recurrent neural networks. DISCUSSION: The identification of clinical phenotypes and prognostic factors for outcomes in pain and disability will be a first step towards pre- and postoperative precision medicine for individuals with hip OA undergoing THA. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05265858. Registered on 04/03/2022.

End-Tidal CO2 in Patients with Panic Disorder, Stress-Related or Functional Syndromes, Versus Healthy Controls.

A dysregulated autonomic stress physiology is hypothesized to play an important role in the etiology and perpetuation of somatic symptoms that cannot be (fully) explained by an organic disease. The aim of this study was to focus on the role of the respiratory system. We examined end-tidal CO2 concentration (PetCO2) in healthy controls (n = 30), patients with panic disorder (n = 36), and patients with stress-related (overstrain; n = 35, burnout; n = 44) or functional syndromes [fibromyalgia (FM) and/or chronic fatigue syndrome (CFS); n = 36]. Participants went through a rest period and a respiratory challenge with recovery, whilst PetCO2 was continuously monitored by a capnograph. Taken together, our results suggest: (1) an overactive respiratory system to be a possible transdiagnostic underlying factor of overstrain, burnout, and panic disorder, and (2) the presence of a less active respiratory fight-flight response in the more chronic and severe functional syndromes (FM/CFS).

The Interoceptive Sensitivity and Attention Questionnaire: Evaluating Aspects of Self-Reported Interoception in Patients With Persistent Somatic Symptoms, Stress-Related Syndromes, and Healthy Controls.

OBJECTIVE: This study aimed to validate the Interoceptive Sensitivity and Attention Questionnaire (ISAQ), a 17-item self-report measure assessing sensitivity and attention to interoceptive signals. METHODS: In study 1, exploratory and confirmatory factor analysis was performed in a student convenience sample (n = 1868). In study 2, ISAQ data of a healthy sample (n = 144) and various patient groups experiencing stress-related syndromes (overstrain, n = 63; burnout, n = 37; panic disorder [PD]. n = 60) and/or persistent somatic symptoms in daily life (irritable bowel syndrome, n = 38; fibromyalgia and/or chronic fatigue syndrome, n = 151; medically unexplained dyspnea [MUD], n = 29) were compared. RESULTS: Three subscales were revealed: (F1) sensitivity to neutral bodily sensations, (F2) attention to unpleasant bodily sensations, and (F3) difficulty disengaging from unpleasant bodily sensations. Overall, patients with fibromyalgia and/or chronic fatigue syndrome and patients with MUD scored significantly higher on F1 (p = .009 and p = .027, respectively) and F2 (p = .002 and p < .001, respectively) than healthy controls. Patients with PD had higher scores on subscales F2 (p < .001) and F3 (p < .001) compared with healthy controls, as well as higher scores on F2 compared with all other patient groups (pPD versus MUD = .008; all other p values < .001). CONCLUSIONS: Interoceptive sensibility-the self-reported aspect of interoception-is not a homogeneous or unitary construct. The subscales of the ISAQ differentiate healthy controls from patients with persistent somatic and/or stress-related complaints in daily life and distinguish different patient groups. The ISAQ can be used as a concise, reliable, and clinically relevant research tool to further disentangle adaptive and maladaptive aspects of interoceptive ability.

The respiratory occlusion discrimination task: A new paradigm to measure respiratory interoceptive accuracy.

Interoception, or the sense of the internal state of the body, is hypothesized to be essential for a wide range of psychobiological processes and the development and perpetuation of several (mental) health problems. However, the study of interoceptive accuracy, the objectively measured capacity to detect or discriminate conscious bodily signals, has been hampered by the use of tasks with questionable construct validity and is often limited to studying interoception solely in the cardiac domain. We developed a novel task to measure interoceptive accuracy in the respiratory domain, the respiratory occlusion discrimination (ROD) task. In this task, interoceptive accuracy is defined as an individual's ability to detect small differences in lengths of short respiratory occlusions, assessed by means of an adaptive staircase procedure. This article describes a validation study (N = 97) aimed at investigating the internal consistency, test-retest reliability, and discriminant validity of the ROD task. The average just noticeable difference of lengths of respiratory occlusion was 74.22 ms, with large inter-individual variability (SD = 37.1 ms). The results of the validation study indicate acceptable internal consistency (Cronbach's alpha = 0.70), 1-week test-retest reliability (r = 0.53), and discriminant validity, as indicated by a lack of correlation between the ROD task and an auditory discrimination task with identical design (r = 0.18), and a weak correlation with breathing behavior (r = -0.27). The ROD task is a promising novel paradigm to study interoceptive accuracy and its role in various psychobiological processes and disorders.

Relationship Between Different Experimental Measures of Distorted Symptom Perception in Functional Syndrome Patients.

OBJECTIVE: Patients with functional somatic syndromes show reduced correspondence between induced physiological changes and self-reported symptoms in a rebreathing paradigm, as well as elevated symptoms unrelated to physiological changes after induction of negative affective states in an affective picture-viewing paradigm. Detailed results of both paradigms separately were published elsewhere. The main goal of the current report is to describe the relationship between the responses to these two paradigms measuring distortions in symptom perception in a well-described sample of patients with fibromyalgia and/or chronic fatigue syndrome. METHODS: Patients (N = 81) with fibromyalgia and/or chronic fatigue syndrome participated in a test session comprising four well-validated paradigms, including the picture-viewing and rebreathing paradigm. Using mixed model analyses, we tested whether the amount of affective modulation of symptom reporting was related to distorted perception of induced dyspnea. In an exploratory way, we assessed the role of several individual difference variables as moderators. RESULTS: There was no relationship between patients' amount of affective modulation of symptom reporting, as assessed with the picture paradigm, and level of distortion in dyspnea perception, as assessed with the rebreathing paradigm (effect of affective modulation in the subjective recovery from induced dyspnea: F1,70 = 0.16, p = .70; time by affective modulation interaction effect: F4,70 = 0.14, p = .97). CONCLUSIONS: Biased symptom reporting in one paradigm is unrelated to biased symptom reporting in the other paradigm, indicating that distortions in symptom perception in patients with functional somatic syndromes are not a trait-like, cross-situationally stable condition, but a versatile dysfunction that is context dependent.

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes.

Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV. Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM. Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.

Reduced selective learning in patients with fibromyalgia vs healthy controls.

Impaired selective fear learning has been advanced as a core mechanism involved in excessive spreading of protective responses such as pain-related fear and avoidance leading to disability in chronic pain conditions. Using the litmus test for selective learning effects, the blocking procedure, we tested the hypothesis that patients with fibromyalgia (FM) show less selective threat learning than healthy controls (HCs). We introduce a novel selective learning task based around a clinical diary scenario. On a trial-by-trial basis, participants rated whether they expected certain situations (A, B, Z, and X) in the diary of a fictive FM patient would trigger pain in that patient. The procedure did not involve any experimental pain induction because the verbal outcomes "pain" or "no pain" were used. During the elemental acquisition phase, one situation was followed by "pain" (A+, eg, "Kim slept badly, and reports pain"), whereas another situation was followed by "no pain" (Z-, eg, "Kim was stressed, and reports no pain"). During the compound acquisition phase, another situation (X), referred to as the blocked stimulus, was presented in compound with a previously pain-eliciting situation and also paired with "pain" (AX+, eg, Kim slept badly" and "Kim has vacuumed," and reports pain). Simultaneously, a novel situation was introduced and also followed by "pain" (B+). Within-group comparisons showed blocking (ie, significant difference between B and X) in the HCs, but not in the patients with FM. This study is the first in directly assessing differences in selective learning between patients with FM and HCs using a blocking procedure.

Perception of induced dyspnea in fibromyalgia and chronic fatigue syndrome.

OBJECTIVE: Dyspnea perception is distorted in patients with medically unexplained dyspnea. The goals of this study were 1) to replicate these results in patients with fibromyalgia and/or chronic fatigue syndrome (CFS), and 2) to investigate predictors of distorted symptom perception within the patient group, with a focus on negative affectivity (NA), psychiatric comorbidity and somatic symptom severity. METHODS: Seventy-three patients diagnosed with fibromyalgia and/or CFS and 38 healthy controls (HC) completed a rebreathing paradigm, consisting of a baseline (60s of room air), a rebreathing phase (150s, gradually increasing ventilation, partial pressure of CO2 in the blood, and self-reported dyspnea), and a recovery phase (150s of room air). Dyspnea, respiratory flow and FetCO2 levels were measured continuously. RESULTS: Patients reported more dyspnea than HC in the recovery phase (p=0.039), but no differences between patients and HC were found in the baseline (p=0.07) or rebreathing phase (p=0.17). No significant differences between patients and HC were found in physiological reactivity. Within the patient group, the effect in the recovery phase was predicted by somatic symptom severity (p=0.046), but not by negative affectivity or by the number of psychiatric comorbidities. CONCLUSION: This study extended earlier findings in patients with medically unexplained dyspnea to patients with fibromyalgia and CFS. This suggests that altered symptom perception is a non-symptom-specific mechanism underlying functional somatic syndromes in general, particularly in patients with high levels of somatic symptom severity. The results are discussed in a predictive coding framework of symptom perception.

Endogenous Pain Modulation: Association with Resting Heart Rate Variability and Negative Affectivity.

Objectives: Several chronic pain syndromes are characterized by deficient endogenous pain modulation as well as elevated negative affectivity and reduced resting heart rate variability. In order to elucidate the relationships between these characteristics, we investigated whether negative affectivity and heart rate variability are associated with endogenous pain modulation in a healthy population. Design, Subjects, and Methods: An offset analgesia paradigm with noxious thermal stimulation calibrated to the individual's pain threshold was used to measure endogenous pain modulation magnitude in 63 healthy individuals. Pain ratings during constant noxious heat stimulation to the arm (15 seconds) were compared with ratings during noxious stimulation comprising a 1 °C rise and return of temperature to the initial level (offset trials, 15 seconds). Offset analgesia was defined as the reduction in pain following the 1 °C decrease relative to pain at the same time point during continuous heat stimulation. Results: Evidence for an offset analgesia effect could only be found when noxious stimulation intensity (and, hence, the individual's pain threshold) was intermediate (46 °C or 47 °C). Offset analgesia magnitude was also moderated by resting heart rate variability: a small but significant offset effect was found in participants with high but not low heart rate variability. Negative affectivity was not related to offset analgesia magnitude. Conclusions: These results indicate that resting heart rate variability (HRV) is related to endogenous pain modulation (EPM) in a healthy population. Future research should focus on clarifying the causal relationship between HRV and EPM and chronic pain by using longitudinal study designs.

Inducing Somatic Symptoms in Functional Syndrome Patients: Effects of Manipulating State Negative Affect.

OBJECTIVE: Induction of negative affective states can enhance bodily symptoms in high habitual symptom reporters among healthy persons and in patients with irritable bowel syndrome. The aims of this study were to replicate this effect in patients with fibromyalgia and chronic fatigue syndrome and to investigate the role of moderators, focusing on alexithymia, negative affectivity, and absorption. METHODS: Patients with fibromyalgia and/or chronic fatigue syndrome (n = 81) and HCs (n = 41) viewed series of neutral, positive, and negative affective pictures. After every picture series, participants filled out a somatic symptom checklist and rated emotions experienced during the picture series on valence, arousal, and perceived control. RESULTS: Patients reported more somatic symptoms after viewing negative pictures (least square mean [LSM] = 19.40, standard error (SE) = 0.50) compared with neutral (LSM = 17.59, SE = 0.42, p < .001) or positive (LSM = 17.04, SE = 0.41, p < .001) pictures, whereas somatic symptom ratings of HCs after viewing negative picture series (LSM = 12.07, SE = 0.71) did not differ from ratings after viewing neutral (LSM = 11.07, SE = 0.59, p = .065) or positive (LSM = 11.10, SE = 0.58, p = .93) pictures. Negative affectivity did not moderate the symptom-enhancing effect of negative affective pictures, whereas the alexithymia factor "difficulty identifying feelings" and absorption did (p = .016 and p = .006, respectively). CONCLUSION: Negative affective states elicit elevated somatic symptom reports in patients experiencing fibromyalgia and/or chronic fatigue syndrome. This symptom-enhancing effect is greater in patients having higher difficulty to identify feelings and higher absorption scores. The results are discussed in a predictive coding framework of symptom perception.

Differentiating progress in a clinical group of fibromyalgia patients during and following a multicomponent treatment program.

OBJECTIVE: Treatments including multiple nonpharmacological components have beneficial effects on the key symptoms of fibromyalgia, although effects are limited and often do not persist. In this study, we examined different patterns of clinical progress and the dynamic interplay between predictors and outcomes over time. METHODS: Fibromyalgia patients (N=153; 135 women) followed a multidisciplinary group program spanning 12weeks, aimed at "regaining control over daily functioning". Anxiety, depression, pain coping and kinesiophobia were used as predictor variables. Outcome variables were pain severity, pain-related disability, physical functioning and functional interference. All variables were assessed at 3 moments: on the first and last day of treatment, and 12weeks after the last day of treatment. Overall treatment effects were analyzed using mixed model analyses. Latent class growth analysis identifying different treatment trajectory classes was used to investigate individual differences in treatment effects. Finally, cross-lagged structural equation models were used to investigate the dynamic interplay between predictors and outcomes over time. RESULTS: Only a fourth to a third of the total group showed improvement on the outcome variables. These patients had lower baseline anxiety, depression and kinesiophobia, and improved more on anxiety, depression and kinesiophobia. Physical well-being had a stronger effect on anxiety and depression than vice versa. Physical functioning predicted relative changes in kinesiophobia, while kinesiophobia predicted relative changes in pain-related disability. CONCLUSION: The results emphasize the importance of tailoring treatments to individual needs in order to improve overall effectiveness of treatment programs.

Can words heal? Using affect labeling to reduce the effects of unpleasant cues on symptom reporting.

Processing unpleasant affective cues induces elevated momentary symptom reports, especially in persons with high levels of symptom reporting in daily life. The present study aimed to examine whether applying an emotion regulation strategy, i.e. affect labeling, can inhibit these emotion influences on symptom reporting. Student participants (N = 61) with varying levels of habitual symptom reporting completed six picture viewing trials of homogeneous valence (three pleasant, three unpleasant) under three conditions: merely viewing, emotional labeling, or content (non-emotional) labeling. Affect ratings and symptom reports were collected after each trial. Participants completed a motor inhibition task and self-control questionnaires as indices of their inhibitory capacities. Heart rate variability was also measured. Labeling, either emotional or non-emotional, significantly reduced experienced affect, as well as the elevated symptoms reports observed after unpleasant picture viewing. These labeling effects became more pronounced with increasing levels of habitual symptom reporting, suggesting a moderating role of the latter variable, but did not correlate with any index of general inhibitory capacity. Our findings suggest that using an emotion regulation strategy, such as labeling emotional stimuli, can reverse the effects of unpleasant stimuli on symptom reporting and that such strategies can be especially beneficial for individuals suffering from medically unexplained physical symptoms.