Hans Knoop

Minimization of childhood maltreatment is common and consequential: results from a large, multinational sample using the childhood trauma questionnaire

Childhood maltreatment has diverse, lifelong impact on morbidity and mortality. The Childhood Trauma Questionnaire (CTQ) is one of the most commonly used scales to assess and quantify these experiences and their impact. Curiously, despite very widespread use of the CTQ, scores on its Minimization-Denial (MD) subscale—originally designed to assess a positive response bias—are rarely reported. Hence, little is known about this measure. If response biases are either common or consequential, current practices of ignoring the MD scale deserve revision. Therewith, we designed a study to investigate 3 aspects of minimization, as defined by the CTQ’s MD scale: 1) its prevalence; 2) its latent structure; and finally 3) whether minimization moderates the CTQ’s discriminative validity in terms of distinguishing between psychiatric patients and community volunteers. Archival, item-level CTQ data from 24 multinational samples were combined for a total of 19,652 participants. Analyses indicated: 1) minimization is common; 2) minimization functions as a continuous construct; and 3) high MD scores attenuate the ability of the CTQ to distinguish between psychiatric patients and community volunteers. Overall, results suggest that a minimizing response bias—as detected by the MD subscale—has a small but significant moderating effect on the CTQ’s discriminative validity. Results also may suggest that some prior analyses of maltreatment rates or the effects of early maltreatment that have used the CTQ may have underestimated its incidence and impact. We caution researchers and clinicians about the widespread practice of using the CTQ without the MD or collecting MD data but failing to assess and control for its effects on outcomes or dependent variables.

Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome

We studied the extent of mitochondrial involvement in chronic fatigue syndrome (CFS) and investigated whether measurement of mitochondrial respiratory chain complex (RCC) activities discriminates between CFS and mitochondrial disorders. Mitochondrial content was decreased in CFS compared to healthy controls, whereas RCC activities corrected for mitochondrial content were not. Conversely, mitochondrial content did not discriminate between CFS and two groups of mitochondrial disorders, whereas ATP production rate and complex I, III and IV activity did, all with higher activities in CFS. We conclude that the ATP production rate and RCC activities can reliably discriminate between mitochondrial disorders and CFS.

Relationship Between Objectively Assessed Physical Activity and Fatigue in Patients With Rheumatoid Arthritis: Inverse Correlation of Activity and Fatigue

Fatigue is generally associated with low physical activity in patients with various chronic medical conditions. However, such an association has not been reported among patients with rheumatoid arthritis (RA). The objectives of this study were to investigate whether daily activity level is associated with fatigue in patients with RA, and whether pain, disability, coping, and/or cognition are associated with the level of daily activity.

Interleukin-1 as a mediator of fatigue in disease: a narrative review

Fatigue is commonly reported in a variety of illnesses, and it has major impact on quality of life. Previously, it was thought that fatigue originates in the skeletal muscles, leading to cessation of activity. However, more recently, it has become clear that the brain is the central regulator of fatigue perception. It has been suggested that pro-inflammatory cytokines, especially interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β), play a prominent role in the development of central fatigue, and several studies have been performed to elucidate the connection between inflammation and these central processes.In this narrative review, mechanisms of action of IL-1 are described, with special attention to its effect on the central nervous system. In addition, we present a summary of studies that (i) investigated the relationship between circulating IL-1α and IL-1β and fatigue severity and/or (ii) evaluated the effect of inhibiting IL-1 on fatigue. We aim to improve the understanding of fatigue in both inflammatory and non-inflammatory illnesses, which could help develop strategies to treat fatigue more effectively.Reviewing the studies that have been performed, it appears that there is a limited value of measuring circulating IL-1. However, inhibiting IL-1 has a positive effect on severe fatigue in most studies that have been conducted.

Reduced complexity of activity patterns in patients with Chronic Fatigue Syndrome: a case control study

BackgroundChronic fatigue syndrome (CFS) is an illness characterised by pervasive physical and mental fatigue without specific identified pathological changes. Many patients with CFS show reduced physical activity which, though quantifiable, has yielded little information to date. Nonlinear dynamic analysis of physiological data can be used to measure complexity in terms of dissimilarity within timescales and similarity across timescales. A reduction in these objective measures has been associated with disease and ageing. We aimed to test the hypothesis that activity patterns of patients with CFS would show reduced complexity compared to healthy controls.MethodsWe analysed continuous activity data over 12 days from 42 patients with CFS and 21 matched healthy controls. We estimated complexity in two ways, measuring dissimilarity within timescales by calculating entropy after a symbolic dynamic transformation of the data and similarity across timescales by calculating the fractal dimension using allometric aggregation.ResultsCFS cases showed reduced complexity compared to controls, as evidenced by reduced dissimilarity within timescales (mean (SD) Renyi(3) entropy 4.05 (0.21) vs. 4.30 (0.09), t = -6.6, p < 0.001) and reduced similarity across timescales (fractal dimension 1.19 (0.04) vs. 1.14 (0.04), t = 4.2, p < 0.001). This reduction in complexity persisted after adjustment for total activity.ConclusionPatients with CFS show evidence of reduced complexity of activity patterns. Measures of complexity applied to activity have potential value as objective indicators for CFS.

Cognitive behavioral therapy positively affects fatigue in patients with multiple sclerosis: Results of a randomized controlled trial

Background: Fatigue is a common symptom in multiple sclerosis (MS) and often restricts societal participation. Cognitive behavioral therapy (CBT) may alleviate MS-related fatigue, but evidence in literature is inconclusive. Objective: To evaluate the effectiveness of CBT to improve MS-related fatigue and participation. Methods: In a multi-center, assessor-masked, randomized controlled trial, participants with severe MS-related fatigue were assigned to CBT or control treatment. CBT consisted of 12 individual sessions with a psychologist trained in CBT, the control treatment consisted of three consultations with a MS nurse, both delivered over 16 weeks. Assessments were at baseline, 8, 16 (i.e. post-intervention), 26, and 52 weeks post-baseline. Primary outcomes were the Checklist Individual Strength-fatigue subscale (CIS20r fatigue) and the Impact on Participation and Autonomy questionnaire (IPA). Data were analyzed according to the intention-to-treat principle, using mixed-model analysis. Results: Between 2011 and 2014, 91 patients were randomized (CBT: n = 44; control: n = 47). Between-group analysis showed a positive post-intervention effect for CBT on CIS20r fatigue (T16: −6.7 (95% confidence interval (CI) = −10.7; −2.7) points) that diminished during follow-up (T52: 0.5 (95% CI = −3.6; 4.4)). No clinically relevant effects were found on societal participation. Conclusion: Severe MS-related fatigue can be reduced effectively with CBT in the short term. More research is needed on how to maintain this effect over the long term.

Causality on longitudinal data: stable specification search in constrained structural equation modeling

Graphical abstractDisplay Omitted HighlightsA finite-sample robust, hypothesis-free, score-based causal discovery algorithm.Reliability scores for inferred causal relationships.An innovative application of multi-objective optimization. Causal modeling has long been an attractive topic for many researchers and in recent decades there has seen a surge in theoretical development and discovery algorithms. Generally discovery algorithms can be divided into two approaches: constraint-based and score-based. The constraint-based approach is able to detect common causes of the observed variables but the use of independence tests makes it less reliable. The score-based approach produces a result that is easier to interpret as it also measures the reliability of the inferred causal relationships, but it is unable to detect common confounders of the observed variables. A drawback of both score-based and constrained-based approaches is the inherent instability in structure estimation. With finite samples small changes in the data can lead to completely different optimal structures. The present work introduces a new hypothesis-free score-based causal discovery algorithm, called stable specification search, that is robust for finite samples based on recent advances in stability selection using subsampling and selection algorithms. Structure search is performed over structural equation models. Our approach uses exploratory search but allows incorporation of prior background knowledge. We validated our approach on one simulated data set, which we compare to the known ground truth, and two real-world data sets for chronic fatigue syndrome and attention deficit hyperactivity disorder, which we compare to earlier medical studies. The results on the simulated data set show significant improvement over alternative approaches and the results on the real-word data sets show consistency with the hypothesis driven models constructed by medical experts.

A comparison of patients with Q fever fatigue syndrome and patients with chronic fatigue syndrome with a focus on inflammatory markers and possible fatigue perpetuating cognitions and behaviour

OBJECTIVE Comparison of Q fever fatigue syndrome (QFS) and chronic fatigue syndrome (CFS) patients, with a focus on markers of inflammation and fatigue-related cognitive-behavioural variables. METHODS Data from two independent prospective studies on QFS (n=117) and CFS (n=173), respectively, were pooled and analyzed. RESULTS QFS patients were less often female, had a higher BMI, and had less often received treatment for depression before the onset of symptoms. After controlling for symptom duration and correcting for differences in diagnostic criteria for QFS and CFS with respect to the level of impairment and the presence of additional symptoms, differences in the proportion of females and BMI remained significant. After correction, QFS patients were also significantly older. In all analyses QFS patients were as fatigued and distressed as CFS patients, but reported less additional symptoms. QFS patients had stronger somatic attributions, and higher levels of physical activity. No differences were found with regard to inflammatory markers and in other fatigue-related cognitive-behavioural variables. The relationship between cognitive-behavioural variables and fatigue, previously established in CFS, could not be confirmed in QFS patients with the exception of the negative relationship between physical activity and fatigue. CONCLUSION Differences and similarities between QFS and CFS patients were found. Although the relationship between perpetuating factors and fatigue previously established in CFS could not be confirmed in QFS patients, the considerable overlap in fatigue-related cognitive-behavioural variables and the relationship found between physical activity and fatigue may suggest that behavioural interventions could reduce fatigue severity in QFS patients.

A web-based cognitive behaviour therapy for chronic fatigue in type 1 diabetes (Dia-Fit): study protocol for a randomised controlled trial

BackgroundFatigue is frequently reported by patients with type 1 diabetes mellitus. A recent study showed that 40 % of patients experienced severe fatigue that lasted for more than six months and was accompanied by substantial impairments in daily functioning. Currently, there is no effective treatment available for chronic fatigue in patients with type 1 diabetes. Cognitive behaviour therapy aimed at cognitions and behaviours that perpetuate fatigue is effective in reducing fatigue in other chronic diseases. Recent research showed that these cognitions and behaviours are also potential determinants of fatigue in type 1 diabetes. We designed Dia-Fit, a web-based cognitive behaviour therapy for severe and chronic fatigue in patients with type 1 diabetes. This patient-tailored intervention is aimed at reducing fatigue by changing cognitions and behaviours assumed to maintain fatigue. The efficacy of Dia-Fit will be investigated in this study.Methods/designA randomised controlled trial will be conducted in 120 patients with type 1 diabetes who are chronically and severely fatigued. Patients will be randomised to a treatment or waiting list group. The treatment group will receive Dia-Fit, a blended care therapy consisting of up to eight internet modules and face-to-face sessions with a therapist during a five-month period. The treatment will be tailored to the fatigue-maintaining cognitions and behaviours that are relevant for the patient and are determined at baseline. The waiting list group will receive Dia-Fit after a waiting period of five months. The primary outcome measure is fatigue severity. Secondary outcome measures are functional impairment and glucose control determined by haemoglobin A1c and blood glucose variability.DiscussionTo our knowledge, this is the first study investigating the efficacy of a cognitive behavioural intervention for chronic fatigue in patients with type 1 diabetes.Trial registrationDutch trial register NTR4312 (10 December 2013).

Testing the efficacy of web-based cognitive behavioural therapy for adult patients with chronic fatigue syndrome (CBIT): study protocol for a randomized controlled trial

BackgroundCognitive behavioural therapy (CBT) is an effective treatment for fatigue and disabilities in patients with chronic fatigue syndrome (CFS). However, treatment capacity is limited. Providing web-based CBT and tailoring the amount of contact with the therapist to the individual needs of the patient may increase the efficiency of the intervention. Web-based CBT for adolescents with CFS has proven to be effective in reducing fatigue and increasing school attendance. In the proposed study the efficacy of a web-based CBT intervention for adult patients with CFS will be explored. Two different formats of web-based CBT will be tested. In the first format named protocol driven feedback, patients report on their progress and receive feedback from a therapist according to a preset schedule. In the second format named support on demand, feedback and support of the therapist is only given when patients ask for it. The primary objective of the study is to determine the efficacy of a web-based CBT intervention on fatigue severity.Method/DesignA randomized clinical trial will be conducted. Two-hundred-forty adults who have been diagnosed with CFS according to the US Centers for Disease Control and Prevention (CDC) consensus criteria will be recruited and randomized to one of three conditions: web-based CBT with protocol driven feedback, web-based CBT with support on demand, or wait list. Feedback will be delivered by therapists specialized in CBT for CFS. Each of the web-based CBT interventions will be compared to a wait list condition with respect to its effect on the primary outcome measure; fatigue severity. Secondary outcome measures are level of disability, physical functioning, psychological distress, and the proportion of patients with clinical significant improvement in fatigue severity. Outcomes will be assessed at baseline and six months post randomization. The web-based CBT formats will be compared with respect to the time therapists need to deliver the intervention.DiscussionAs far as we know this is the first randomized controlled trial (RCT) that evaluates the efficacy of a web-based CBT intervention for adult patients with CFS.Trial registrationNTR4013