[From MUPS to PSS: advancing insight]. / Van SOLK naar ALK.

Since 2021 experts advocate for the abolishment of the term Medically Unexplained Physical Symptoms (MUPS) and the use of Persistent Somatic Symptoms (PSS). This article elucidates the difference between MUPS and PSS, as well as the relation to other relevant concepts like functional syndromes and somatic symptom disorder. Because the term MUPS emphasizes that no somatic cause for the symptoms has been found, it is commonly concluded that the symptoms are 'psychological' in line with the body/mind dualism. This leads to excessive focus on psychosocial contributing factors in MUPS, and too little in PSS in the context of a known somatic disorder. With the term PSS, the question whether there is a somatic cause for the symptoms is not the key issue, but the persistence of the symptoms. This allows for personalised diagnostics and treatment according to the biopsychosocial model.

Stigma in functional neurological disorder (FND) - A systematic review.

OBJECTIVE: The purpose of this systematic review was to evaluate stigma and Functional Neurological Disorder (FND) regarding: 1) prevalence and associated factors, 2) the nature and context of stigma in FND, and 3) stigma-reduction interventions. METHODS: We searched four relevant databases from inception to December 2023, using search terms relevant to FND and stigma themes. We employed the method of synthesis by "aggregation and configuration" to synthesise and analyse the data into emergent themes. RESULTS: We found 127 studies, spanning 148 countries, involving 18,886 participants. Of these, 4889 were patients, 13,123 were healthcare professionals, and 526 were caregivers. Quantitatively, stigma has been mainly studied in patients with functional seizures, and was higher than patients with epilepsy in three studies. Stigma experienced by patients is associated with poorer quality of life and caregiver burden. We found 10 themes and 29 subthemes revealing stigma as a systemic process, with intrapersonal, interpersonal and structural aspects. Few studies examined the perspective of caregivers, the public or online community. We identified six anti-stigma interventions. CONCLUSION: Stigma in FND is a layered process, and affects patient quality of life and provision of care. Stigma needs to be addressed from the top structures, at governmental level, so that appropriate care pathways can be created, giving patients with FND parity of esteem with other medical conditions.

Strategies to improve implementation of collaborative care for functional disorders and persistent somatic symptoms: A qualitative study using a Research World Café design.

INTRODUCTION: Persistent somatic symptoms and functional disorders (PSS/FD) are often complex conditions requiring care from multiple disciplines. One way of bringing the different disciplines together is through collaborative care. Little is known about the implementation barriers faced and relevant strategies to tackle the barriers in this field. Therefore, using expert knowledge, we aim to develop realistic strategies for dealing with implementation barriers of collaborative care in PSS/FD. METHODS: The Research World Café method is a single-session, expert-based method with multiple focus-groups forming and reforming to answer a set of inter-related questions, under the guidance of moderators. Using this method, participants involved in PSS/FD care across different areas of healthcare in the Netherlands developed several realistic strategies for dealing with ten implementation barriers for collaborative care in PSS/FD that were previously identified in a Delphi study. Strategies were grouped into strategy clusters using a card-sorting task. RESULTS: Thirty-three participants took part, representing ten different disciplines, most commonly physiotherapists, psychologists, and physicians. In total, 54 strategies, identified in response to the ten barriers, were grouped into eight strategy clusters. The strategy clusters were professional education, communication, care coordination, care pathways, joint consults, funding, patient involvement, and prevention. CONCLUSION: We identified a number of useful strategies for dealing with implementation barriers for collaborative care in PSS/FD. Many strategies provided ways to deal with multiple barriers at once. The effects of applying these strategies in collaborative care in PSS/FD will need testing through implementation studies, as well as in other areas needing multidisciplinary care.

Quality indicators for collaborative care networks in persistent somatic symptoms and functional disorders: a modified delphi study.

BACKGROUND: Care for persistent somatic symptoms and functional disorders (PSS/FD) is often fragmented. Collaborative care networks (CCNs) may improve care quality for PSS/FD. Effectiveness likely depends on their functioning, but we lack a straightforward quality evaluation system. We therefore aimed to develop quality indicators to evaluate CCNs for PSS/FD. METHOD: Using an online three-round modified Delphi process, an expert panel provided, selected and ranked quality indicators for CCNs in PSS/FD. Recruited experts were diverse healthcare professionals with relevant experience in PSS/FD care in the Netherlands. RESULTS: The expert panel consisted of 86 professionals representing 15 disciplines, most commonly physiotherapists, psychologists and medical specialists. 58% had more than 10 years experience in PSS/FD care. Round one resulted in 994 quotations, which resulted in 46 unique quality indicators. These were prioritised in round two and ranked in round three by the panel, resulting in a final top ten. The top three indicators were: "shared vision of care for PSS/FD", "pathways tailored to the individual patient", and "sufficiently-experienced caregivers for PSS/FD". CONCLUSIONS: The identified quality indicators to evaluate CCNs in the field of PSS/FD can be implemented in clinical practice and may be useful in improving services and when assessing effectiveness.

Characteristics of collaborative care networks in functional disorders: A systematic review.

OBJECTIVE: Functional disorders (FD) are complex conditions, for which multidisciplinary involvement is often recommended. Collaborative care networks (CCN) may unlock the potential of the multidisciplinary team (MDT) in FD care. To understand what characteristics should be part of CCNs in FD, we studied the composition and characteristics of existing CCNs in FD. METHODS: We performed a systematic review following PRISMA guidelines. A search of PubMed, WebofScience, PsycInfo, SocINDEX, AMED and CINAHL was undertaken to select studies describing CCNs in FD. Two reviewers extracted characteristics of the different CCNs. Characteristics were classified as relating to structure and processes of networks. RESULTS: A total of 62 studies were identified representing 39 CCNs across 11 countries. Regarding structural characteristics, we found that most networks are outpatient, secondary-care based, with teams of between two and 19 members. Medical specialists were most commonly involved and the typical team leads as well as main patient contacts were general practitioners (GPs) or nurses. Regarding processes, collaboration was demonstrated mostly during assessment, management and patient education, less often during rehabilitation and follow-up, mostly using MDT meetings. CCNs provided a wide range of treatment modalities, reflecting a biopsychosocial approach, including psychological therapies, physiotherapy and social and occupational therapy. CONCLUSION: CCNs for FD are heterogeneous, showing a wide variety of structures as well as processes. The heterogeneity of results provides a broad framework, demonstrating considerable variation in how this framework is applied in different contexts. Better development of network evaluation, as well as professional collaboration and education processes is needed.

Individual treatment goals and factors influencing goal attainment in patients with somatic symptom disorder from the perspective of clinicians: A concept mapping study.

OBJECTIVE: Overviews of treatment goals and influencing factors may support shared decision making and optimize customized treatment to the patient with somatic symptom disorder (SSD). The aim of this study was to identify and structure comprehensive sets of treatment goals and factors influencing goal attainment in patients with SSD from the perspective of clinicians. METHODS: Using a concept mapping procedure, clinicians participated in interviews (N = 17) and card sorting tasks comprising 55 treatment goals and 55 factors influencing goal attainment (N = 38). RESULTS: We identified four overarching categories (A to D) of nine clusters (1 to 9) of treatment goals: A. empowerment (A1. personal values, A2. committed action, A3. self-esteem), B. skill improvement (B4. interpersonal skills, B5. emotion and stress regulation), C. symptom reduction (C6. dysfunctional beliefs, C7. somatic symptoms, C8. psychological symptoms), and D9. active and structured lifestyle. Also, we identified four overarching categories (A to D) of nine clusters (1 to 9) of factors influencing goal attainment: A1. therapeutic alliance, B. social and everyday context (B2. [family] system, B3. meaningful daily schedule, B4. social and economic circumstances), C. ability to change (C5. externalizing tendency, C6. reflective and psychological skills, C7. perspective and motivation), and D. psychological vulnerability (D8. vulnerable personality, D9. [psychiatric] comorbidity). CONCLUSION: The overviews of treatment goals and factors influencing goal attainment reflect different paradigmatic backgrounds of clinicians. The results can be used, in combination with the perspective of the patient, to define treatment goals, and to monitor and evaluate change in outcomes.

Development and psychometric evaluation of the Transdiagnostic Decision Tool: matched care for patients with a mental disorder in need of highly specialised care.

BACKGROUND: Early identification of patients with mental health problems in need of highly specialised care could enhance the timely provision of appropriate care and improve the clinical and cost-effectiveness of treatment strategies. Recent research on the development and psychometric evaluation of diagnosis-specific decision-support algorithms suggested that the treatment allocation of patients to highly specialised mental healthcare settings may be guided by a core set of transdiagnostic patient factors. AIMS: To develop and psychometrically evaluate a transdiagnostic decision tool to facilitate the uniform assessment of highly specialised mental healthcare need in heterogeneous patient groups. METHOD: The Transdiagnostic Decision Tool was developed based on an analysis of transdiagnostic items of earlier developed diagnosis-specific decision tools. The Transdiagnostic Decision Tool was psychometrically evaluated in 505 patients with a somatic symptom disorder or post-traumatic stress disorder. Feasibility, interrater reliability, convergent validity and criterion validity were assessed. In order to evaluate convergent validity, the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and the ICEpop CAPability measure for Adults (ICECAP-A) were administered. RESULTS: The six-item clinician-administered Transdiagnostic Decision Tool demonstrated excellent feasibility and acceptable interrater reliability. Spearman's rank correlations between the Transdiagnostic Decision Tool and ICECAP-A (-0.335), EQ-5D-5L index (-0.386) and EQ-5D-visual analogue scale (-0.348) supported convergent validity. The area under the curve was 0.81 and a cut-off value of ≥3 was found to represent the optimal cut-off value. CONCLUSIONS: The Transdiagnostic Decision Tool demonstrated solid psychometric properties and showed promise as a measure for the early detection of patients in need of highly specialised mental healthcare.

Death anxiety and its association with hypochondriasis and medically unexplained symptoms: A systematic review.

OBJECTIVE: To systematically review of the available literature to (1) examine the association between death anxiety and hypochondriasis and (2) examine the association between death anxiety and medically unexplained symptoms (MUS). METHODS: A systematic literature search was conducted in Embase, PsycINFO, Pubmed and Ovid databases and reference lists of selected articles. Articles were included when the research population concerned people with hypochondriasis and/or MUS in who death anxiety was assessed by a validated research method. Two independent reviewers verified that the studies met the inclusion criteria, assessed the quality of the studies and extracted relevant characteristics and data. The data were descriptively analysed. RESULTS: Of the 1087 references identified in the search, six studies on the association between death anxiety and hypochondriasis and three studies on the association between death anxiety and MUS met inclusion criteria. All studies found a positive association of death anxiety with hypochondriasis and/or MUS. The design of all studies was cross-sectional and the overall quality of the studies was low. The influence of age or sex on these associations was not analysed in any of the studies. Given the diversity in setting, population, study design, and methods used, a meta-analysis was not possible. CONCLUSION: All studies found a positive association of death anxiety with hypochondriasis and/or MUS. Acknowledging that death anxiety may play a prominent role in hypochondriasis/MUS populations, future research should address (potentially modifiable) determinants of death anxiety in these populations.

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.

Age- and sex-specific associations between adverse life events and functional bodily symptoms in the general population.

OBJECTIVE: To test age- and sex-specific associations between adverse life events and functional bodily symptoms (FBS) in the general population. METHODS: In a population-based cohort, 964 participants (mean age 55 years SD 11, 48% male) completed two measurements waves of the present study. Lifetime exposure to 12 adverse life events was assessed through a modified version of the List of Threatening Experiences. Stress-sensitive personality was assessed with the 12-item neuroticism scale of the Eysenck Personality Questionnaire-Revised. Socio-economic status was retrieved from questionnaires. Participants completed the somatization section of the Composite International Diagnostic Interview to survey the presence of 42 FBS in the previous year. RESULTS: Regression analyses, adjusted for age, revealed that lifetime scores of adverse life events were significantly associated with FBS in the previous year, an association that was nearly identical for females (beta=0.18, t=4.07, p<0.01) and males (beta=0.19, t=4.24, p<0.01). This association remained statistically significant when stress-sensitive personality and socio-economic status were added to the model. Associations between adverse life events during childhood and FBS were statistically significant in females (beta=0.13, t=2.90, p=0.04) but not in males (beta=0.06, t=1.24, p=0.22), whereas there was a stronger association with adverse life events during adulthood in males (beta=0.20, t=4.37, p<0.01) compared to females (beta=0.15, t=3.38, p=0.01). Life events in the previous year were not associated with FBS in the previous year. CONCLUSION: Adverse life events during lifetime were associated with FBS in the previous year. This association was dependent on age and sex but largely independent of having a stress-sensitive personality or low socio-economic status. Future studies could adopt a life course perspective to study the role of adverse life events in FBS.

[No quetiapine for sleeping disorders]. / Geen quetiapine bij slaapstoornissen.

The prescribing of low doses of quetiapine for the treatment of sleeping disorders appears to be widespread. Recently, in a systematic literature review on low-dose quetiapine use for the treatment of sleeping disorders, it was concluded that evidence for its efficacy is currently lacking. Furthermore, quetiapine is probably associated with potentially severe adverse effects, also at low doses. In conclusion, sufficient scientific evidence that justifies the current practice of off-label prescribing of low-dose quetiapine for the treatment of sleeping disorders is insufficient; further research into its efficacy and safety is needed.

Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders.

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the most investigated biological risk marker in functional somatic disorders (FSDs), such as chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS). Our aim was to assess whether there is an association between basal hypocortisolism and FSD and to identify potential moderators of this association. Meta-analysis on 85 studies revealed that although basal cortisol levels were generally lower in FSD subjects compared to controls, this association did not reach statistical significance (SMD -0.07, 95% CI -0.17 to 0.04, p=0.241). However, when the three FSD were assessed separately, statistically significant basal hypocortisolism was observed in CFS subjects compared to controls (SMD -0.14, 95% CI -0.28 to 0.00, p=0.047), but not in FM or IBS. When all potential moderators were entered into a meta-regression analysis, only type of FSD and female gender were significant independent predictors of basal hypocortisolism. In conclusion, we did not find evidence to consider all three main FSD as hypocortisolemic disorders, as significant reduction in basal cortisol compared to healthy controls was only found in CFS and in females with FM, but not in IBS.

More than the sum of its parts: meta-analysis and its potential to discover sources of heterogeneity in psychosomatic medicine.

Meta-analyses may contribute to more reliable knowledge about the existence of certain relations in the area of psychosomatic research. Surprisingly, the increasing popularity of meta-analysis is not reflected in the number of meta-analyses of observational studies published in Psychosomatic Medicine. This may be due to the specific difficulties that apply to meta-analyses of observational research. The aim of this paper is to provide a nontechnical overview of the principles of meta-analysis applied to observational research. We will highlight general principles of meta-analysis and discuss the major threats to its validity, with an emphasis on its specific merits and pitfalls for psychosomatic research, using several examples. We conclude that meta-analysis is a relatively simple technique, leaving little reason for not routinely applying it when performing a systematic review. An adequately conducted meta-analysis may not only provide a summary estimate of a certain association, but it has additional value in discovering relevant confounders, mediators, and moderators, as well as identifying areas of research that require more attention.

Dysfunction of stress responsive systems as a risk factor for functional somatic syndromes.

The etiology of functional somatic syndromes or disorders (FSDs) is generally considered to be a multifactorial interplay between psychological, biological, and social factors. One of the most investigated biological factors is stress responsive system dysfunction. Despite more than twenty years of research of the autonomic nervous system and the hypothalamic-pituitary-adrenal axis, however, it is yet unknown whether dysfunctions in these systems play a causal role in the etiology of FSDs and whether they are generic or FSD-specific. In this review, we will give an overview of available evidence on whether or not alterations in these stress responsive systems can be considered causal risk factors of FSDs. We conclude that although not necessary factors for FSDs in general, lowered cardiac vagal activity and hypocortisolism may be pivotal in the etiology and treatment strategy in subgroups of subjects with a FSD. Such subgroups need to be better identified.

Age-specific associations between cardiac vagal activity and functional somatic symptoms: a population-based study.

BACKGROUND: Functional somatic symptoms (FSS) are symptoms not explained by underlying organic pathology. It has frequently been suggested that dysfunction of the autonomic nervous system (ANS) contributes to the development of FSS. We hypothesized that decreased cardiac vagal activity is cross-sectionally and prospectively associated with the number of FSS in the general population. METHODS: This study was performed in a population-based cohort of 774 adults (45.1% male, mean age +/- SD 53.5 +/- 10.7 years). Participants completed the somatization section of the Composite International Diagnostic Interview surveying the presence of 43 FSS. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF), reflecting cardiac vagal activity. Follow-up measurements of HRV-HF and FSS were performed approximately 2 years later. RESULTS: Linear regression analyses, with adjustments for gender, age, body mass index, anxiety, depression, smoking, alcohol use, and frequency of exercise, revealed an interaction of cardiac vagal activity with age: HRV-HF was negatively associated with FSS in adults 52 years (beta = 0.13, t = 2.51, p = 0.012). Longitudinal analysis demonstrated a similar pattern. CONCLUSIONS: Decreased cardiac vagal activity is associated with a higher number of FSS in adults aged 52 years needs further exploration. The role of age should be acknowledged in future studies on ANS function in the etiology of FSS.

Is high-sensitive C-reactive protein a biomarker for functional somatic symptoms? A population-based study.

Functional somatic symptoms (FSS) are symptoms unexplained in terms of underlying organic pathology. Alterations in the immune system function may be associated with FSS via induction of sickness behavior. We aimed to investigate whether low-grade immune system activation is positively associated with FSS in a population-based cohort of 881 adults (46% male, mean age 53.0, SD 11.4). Participants completed the somatization section of the Composite International Diagnostic Interview surveying the presence of 43 FSS. Innate immune function was assessed by measuring high-sensitive C-reactive protein (hs-CRP). Follow-up measurements of hs-CRP and FSS were performed approximately 2years later. Regression analyses, with adjustments for gender, age, body mass index, anxiety, depression, smoking, alcohol use, and frequency of exercise, did not reveal a cross-sectional association (beta=0.01, t=0.40, p=0.693) or longitudinal association (beta=-0.03, t=-0.93, p=0.352) between hs-CRP and the total number of FSS. When examining different bodily clusters of FSS, hs-CRP was not associated with the gastrointestinal FSS cluster, but the association approached statistical significance for the general FSS cluster (OR 1.08, 95% CI 0.98-1.18) and musculoskeletal FSS cluster (OR 1.08, 95% CI 0.99-1.17). For the latter association, exploratory analyses revealed that mainly the pure musculoskeletal complaints were responsible (OR 1.12, 95% CI 1.03-1.21). We conclude that the level of hs-CRP is not a biomarker for the total number of FSS in the general population. The association between hs-CRP and musculoskeletal and general FSS needs further study.

As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders.

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD)=-0.32, 95% CI -0.63 to -0.01, p=0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry=0.01, 95% CI -0.34 to 0.36, p=0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.

Dysfunction of the hypothalamic-pituitary-adrenal axis and functional somatic symptoms: a longitudinal cohort study in the general population.

In persons with functional somatic symptoms (FSS), no conventionally defined organic pathology is apparent. It has been suggested that complex interactions of psychological, physiological, and social factors are involved in the etiology of FSS. One of the physiological mechanisms that may contribute to FSS is the function of the hypothalamic-pituitary-adrenal (HPA)-axis. This study investigates the association of HPA-axis function with cross-sectional presence and prospective development of FSS in the general population. This study was performed in a population-based cohort of 741 male and female adults (mean age 53.1, S.D. 10.9). Participants completed the somatization section of the Composite International Diagnostic Interview (CIDI) in which the presence of 43 FSS is surveyed. In addition to the total number of FSS, bodily system FSS clusters with musculoskeletal, gastrointestinal, cardiorespiratory, and general symptoms were constructed. HPA-axis function was assessed by measuring 24-h urinary free cortisol (24-h UFC) excretion. Follow-up measurements were performed approximately 2 years later. All analyses were adjusted for age, gender, body mass index, smoking, alcohol use, depression, exercise frequency, and urinary volume. Regression analysis detected no cross-sectional association between 24-h UFC excretion and the number of FSS (beta=-0.021, t=-0.521, p=0.603). In addition, 24-h UFC excretion was not associated with any of the bodily system FSS clusters (all p>0.050). Furthermore, 24-h UFC excretion did not predict new-onset FSS in the 2-year follow-up period (beta=0.021, t=0.566, p=0.572). We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population. We conclude that this study does not provide evidence for an association between altered HPA-axis function, as indexed by 24-h UFC, and FSS in the general population.