Factors associated with having previously received a diagnosis of fibromyalgia, chronic fatigue syndrome and irritable bowel syndrome: A cross sectional DanFunD study.

OBJECTIVES: Fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome are highly prevalent conditions and part of the functional somatic syndromes (FSS) diagnosis, that are classified under the unifying umbrella term functional somatic disorder (FSD). Multiple factors are associated with FSD symptom development; However, few studies have explored these associations in relation to the diagnosis status. This study aims to examine associations with a previously received FSS diagnosis from a physician in participants fulfilling the FSD diagnostic criteria in a population-based sample. METHODS: This research employs a comprehensive observational approach using a cross sectional design with data from the DanFunD part two cohort. Information about received FSS diagnoses was obtained from self-reported questionnaires. Participants fulfilling the FSD diagnostic criteria were identified with both self-reported questionnaires and diagnostic interviews. Validated questionnaires were used to assess the examined factors. RESULTS: 1704 cases fulfilled the diagnostic criteria for an FSD according to questionnaires or interviews in the DanFunD study. In participants fulfilling the diagnostic criteria, having previously received an FSS diagnosis by a physician was strongly associated with female sex, negative illness perceptions and poor health-related quality of life for questionnaire and interview-based diagnoses. Less consistent associations were observed for lower socioeconomic status, anxiety, and adverse life events. CONCLUSION: Previously received FSS diagnoses showed associations with multiple factors with a particular strong association with female sex and poor health related quality of life.

Efficacy of patient education and duloxetine, alone and in combination, for patients with multisystem functional somatic disorder: Study protocol for the EDULOX trial.

BACKGROUND: Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. METHODS: This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. CONCLUSION: The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www. CLINICALTRIALS: gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.

Hair cortisol and self-perceived stress in adolescents with multi-system functional somatic disorders.

BACKGROUND: Long-term stress causing altered hypothalamic-pituitary-adrenal (HPA) axis dynamics with cortisol dysfunction may be involved in the pathophysiology of functional somatic disorders (FSD), but studies on adolescents with multi-system FSD are lacking. Therefore, we investigated: 1) whether hair cortisol concentration (HCC) differentiates adolescents with multi-system FSD from a) a population-based sample and b) a subgroup derived from the sample reporting a high physical symptom load, and 2) whether FSD population HCC is associated with primary symptom presentations and self-perceived stress. METHODS: We used data from a clinical sample with multi-system FSD (N = 91, age 15-19 years) and a population-based sample (N = 1,450, age 16-17 years) including a subgroup with top 10% total scores on physical symptoms (N = 147). Density plots and multiple linear regression were applied to compare HCC between groups. In the clinical sample, multiple linear regression was employed to assess the association between HCC and primary symptom clusters and self-perceived stress. RESULTS: Median HCC was lower in the clinical sample than in the population-based sample (ß = 0.80 (95%CI: 0.66, 0.97)), but not significantly different from median HCC in the derived subgroup (ß = 0.84 (95%CI: 0.66, 1.07)). In the clinical sample, HCC was not significantly associated with primary symptom clusters (F(2, 82) = 0.13, p = 0.88) or self-perceived stress (F(4, 83) = 1.18, p = 0.33). CONCLUSION: Our findings indicate that HCC is lowered in adolescents with multi-system FSD but not significantly associated with primary symptom presentations or self-perceived stress. Future studies including multiple measures of HPA axis dynamics alongside psychological measures may further elucidate the role of long-term stress in FSD. TRIAL REGISTRATION: The AHEAD study was pre-registered at ClinicalTrials.gov (NCT02346071), 26/01/2015.

Neuroticism, perceived stress, adverse life events and self-efficacy as predictors of the development of functional somatic disorders: longitudinal population-based study (DanFunD).

BACKGROUND: Functional somatic disorder (FSD) is a unifying diagnosis that includes functional somatic syndromes such as irritable bowel, chronic widespread pain (CWP) and chronic fatigue. Several psychological factors are associated with FSD. However, longitudinal population-based studies elucidating the causal relationship are scarce. AIMS: To explore if neuroticism, perceived stress, adverse life events (ALEs) and self-efficacy can predict the development of FSD over a 5-year period. METHOD: A total of 4288 individuals who participated in the DanFunD baseline and 5-year follow-up investigations were included. FSD was established at both baseline and follow-up, with symptom questionnaires and diagnostic interviews. Neuroticism was measured with the short-form NEO Personality Inventory, perceived stress with the Cohen's Perceived Stress Scale, ALEs with the Danish version of the Cumulative Lifetime Adversity Measure and self-efficacy with the General Self-Efficacy Scale. Associations were investigated with multiple logistic regression models. RESULTS: Perceived stress predicted incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.04-1.17). Neuroticism predicted incident FSD and chronic fatigue (odds ratios: 1.03-1.16). ALEs predicted incident FSD, CWP and chronic fatigue (odds ratios: 1.06-1.18). An increase in perceived stress from baseline to follow-up was associated with incident FSD, irritable bowel, CWP and chronic fatigue (odds ratios: 1.05-1.22). Contrary, an increase in self-efficacy seemed to be a protective factor (odds ratios: 0.89-0.99). CONCLUSIONS: High neuroticism, high perceived stress and a high number of ALEs are risk factors for the development of FSD. Particularly perceived stress seems to be an important contributor to the onset of FSD.

Internet-Delivered Therapy for Parents With Health Anxiety by Proxy: Protocol for a Single-Case Experimental Design Study.

BACKGROUND: Health anxiety (HA) by proxy is described as parents' obsessive worries that their child is severely ill although this is not medically confirmed. Research on HA by proxy suggests that it is highly distressing for the parent and that the child may be at risk of developing maladaptive symptom coping strategies. No targeted treatment for this group exists. We developed PROXY, an 8-week psychological internet-delivered treatment for parents with HA by proxy. The treatment components of PROXY are informed by cognitive behavioral therapy as well as acceptance and commitment therapy, and it was developed in collaboration with parents experiencing HA by proxy and clinical experts. OBJECTIVE: This paper describes the protocol for a study investigating the potential effects of PROXY on parents' worries about their children's health using a single-case experimental design (SCED). METHODS: Five parents clinically evaluated as experiencing HA by proxy will be included. A replicated randomized SCED study will be conducted in which each participant will be randomized to receive treatment after a baseline period of between 7 and 26 days (phase A). The treatment phase duration is 8 weeks for all participants (phase B), followed by a follow-up phase lasting between 14 and 33 days (phase C), ensuring that all participants remain in the study for 96 days. Participants will report daily anxiety level by SMS text message throughout the study. They will also answer self-report questionnaires, including questions on HA by proxy and own HA, 4 times during the study. Data will be submitted to structured visual analysis to inspect anxiety level, the variability of anxiety, trends, the overlap of data points among phases, when effects occur, and the consistency of data patterns across participants. Furthermore, randomization tests will be conducted for each participant to test the null hypothesis that PROXY will have no effect on participants' anxiety. RESULTS: The recruitment of parents began in June 2022. As of March 2, 2023, a total of 4 parents have been included in the study. Data collection was expected to cease in April 2023. CONCLUSIONS: To the best of our knowledge, this protocol describes the only study of treatment for HA by proxy. As the prevalence of this condition is still unknown, a SCED was chosen because this method allows the inclusion of very few participants while still providing information on effects and treatment courses. Conducting the study with a replicated randomized phase design enables methodologically sound testing despite the inclusion of very few participants. The results will inform researchers on individual treatment courses and effects, which may direct future research in terms of the possible mechanisms of change, ideas for how to refine the treatment content, and how the treatment may be offered to patients in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04830605; https://clinicaltrials.gov/study/NCT04830605. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46927.

Prevention of hazardous use of alcohol among high school students: a study protocol for the randomized controlled trial 'Our choice'.

BACKGROUND: Adolescent hazardous alcohol use is prevalent and has serious short- and long-term consequences. The trial 'Our Choice' examines efficacy, feasibility and acceptability of prevention interventions targeting school, parent, and student levels at Danish high schools. We hypothesize that students in a structural intervention (school and parent levels) reduce hazardous alcohol use and related health behaviors compared to students in an assessment only control group 12 months post baseline; and that adding group-based Motivational Interviewing (group MI) yields further improvements. The study examines the efficacy of interventions targeting multiple levels with the aim of providing novel insights into prevention of adolescent hazardous alcohol use and related health outcomes. METHOD: The study employs a parallel group cluster randomized controlled trial design with three conditions: (1) structural condition targeting school and parent levels, (2) structural condition combined with group MI which also targets the student level, and (3) assessment-only control condition. A participatory approach is used to adapt and develop interventions. Sixteen high schools in Denmark and about N = 3100 first-year students (15-18 years) enrolled in high school in August 2023 will be recruited. Data will be collected via online questionnaires pre-interventions (baseline), 2, 6, 9 and 12 month post baseline and analyzed with generalized linear mixed models. The primary outcome is past month high intensity drinking; secondary outcomes are alcohol use, alcohol-related consequences, well-being, tobacco, and illegal substance use. Feasibility and acceptability will be assessed via surveys (students) and interviews (high school staff) to inform future implementation. DISCUSSION: 'Our Choice' is the first trial to compare the efficacy of a structural intervention targeting school- and parent levels to an intervention targeting these levels and the student level via group MI - on hazardous drinking and related health outcomes among students. Preventing and reducing hazardous alcohol use during adolescence is crucial due to the short- and long-term negative consequences. The tested interventions can be implemented at low cost. The study has significant implications for adolescent health and well-being and has potential to inform evidence-based decisions on alcohol prevention policy, education, and health professions. TRIAL REGISTRATION NUMBER: The trial was retrospectively registered at ClinicalTrials.gov on August 24th, 2023. TRIAL REGISTRATION NUMBER: ID NCT06018389.

Clinical Impact of Systematic Assessment and Psychoeducation in Specialized Treatment of Adolescents with Severe Functional Somatic Disorders: Results from the AHEAD Study.

Functional somatic disorders (FSD), characterized by persistent and disabling physical symptoms, are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study describes the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) received systematic assessment (4 h) and a subsequent psychiatric consultation (1.5 h). Clinical characteristics included self-reported physical health, symptom severity, illness perception, illness-related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment, 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen in symptom severity, illness worry, negative illness perceptions, illness-related limiting behavior, and psychological inflexibility. The results emphasize that systematic assessment and psychoeducation are important in their own right in the specialized treatment of adolescents with severe FSD.

High Perceived Stress and Low Self-Efficacy are Associated with Functional Somatic Disorders: The DanFunD Study.

Objective: Several psychological factors have been proposed to be associated with functional somatic disorders (FSD) including functional somatic syndromes, such as irritable bowel, chronic widespread pain, and chronic fatigue. However, large randomly selected population-based studies of this association are sparse. This study aimed to investigate the association between FSD and perceived stress and self-efficacy, respectively, and to investigate if FSD differed from severe physical diseases on these aspects. Methods: This cross-sectional study included a random sample of the adult Danish population (n = 9656). FSD were established using self-reported questionnaires and diagnostic interviews. Perceived stress was measured with Cohen's Perceived Stress Scale and self-efficacy with the General Self-Efficacy Scale. Data were analysed with generalized linear models and linear regression models. Results: FSD were associated with higher perceived stress and lower self-efficacy, especially for the multi-organ and the general symptoms/fatigue FSD types and for chronic fatigue. However, controlling for the personality trait neuroticism altered the associations with self-efficacy so it became insignificant. The analysis did not support an important interaction between perceived stress and self-efficacy on the likelihood of having FSD. Individuals with FSD presented levels of perceived stress that were not equal, ie higher, to those in individuals with severe physical diseases. Conclusion: FSD were positively associated with perceived stress and negatively associated with self-efficacy. Our study may point to stress being part of the symptomatology of FSD. This underlines the severity of having FSD and stresses the relevance of the resilience theory in the understanding of the condition.

Can the bodily distress syndrome (BDS) concept be used to assess functional somatic symptoms in adolescence?

OBJECTIVE: Bodily Distress Syndrome (BDS) represents a new research concept for adult patients with various functional somatic syndromes. We evaluated the utility of the BDS research concept and the associated BDS-25-checklist as a screening tool for diverse functional somatic symptoms (FSS) in adolescence by investigating: 1) the psychometric and factorial structures of the checklist, 2) symptom cluster patterns and 3) illness classification and associations with emotional psychopathology and sociodemographic factors. METHODS: This cross-sectional study obtained data from the 16/17-year follow-up (N = 2542) of the general population Copenhagen Child Cohort 2000 (CCC2000). We used self-reported questionnaires to assess physical symptoms (the BDS-25 checklist), overall health (KidScreen), emotional psychopathology (Spence Children's Anxiety Scale; The Mood and Feelings Questionnaire), and illness worry (Whiteley-6 Index), and utilized data from Danish national registers to assess sociodemographic factors. RESULTS: The BDS-25 checklist items displayed satisfactory psychometric data quality. Factor analyses revealed a similar four-factor model as reported in adults (factor loadings λ ≥0.5), representing distinct BDS symptom clusters: cardio-pulmonary, gastro-intestinal, musculoskeletal and general symptoms. Latent class analyses revealed a model with three latent classes, i.e. probable no to mild BDS, probable moderate, single-organ BDS and probable severe, multi-organ BDS, displaying acceptable class quality (Entropy = 0.904). Trend analyses revealed sociodemographic group differences across latent classes. Increased emotional psychopathology was associated with more pronounced BDS symptoms. CONCLUSION: Our findings support the BDS concept with four symptom clusters and three illness severity groups (no BDS, single- organ and multi-organ BDS) to screen for FSS in adolescence.

Group-based compassion-focused therapy for prolonged grief symptoms in adults - Results from a randomized controlled trial.

Prolonged grief disorder is a debilitating condition, which affects approximately one out of ten who lose a loved one. While existing meta-analyses have synthesized evidence regarding the overall effect of psychological interventions for pathological grief across different types of psychotherapy, it remains clinically relevant to explore whether specific types of psychological interventions are efficacious in the treatment of grief. The present study investigated the efficacy of group-based Compassion-Focused Therapy (CFT) for adults who had lost a spouse or a parent, and who reported clinically relevant levels of prolonged grief symptoms (PGS) at 11 months post-loss. A total of 82 participants were randomized to the CFT group (n = 42) or the waitlist control (n = 40). Time × group interactions showed no statistically significant effects of the intervention on the primary outcome PGS at post-intervention or 6-month follow-up. Likewise, no statistically significant effects were found for any of the secondary outcomes or process variables, with the exception of posttraumatic stress symptoms and self-reassurance. Taken together, in the present study group-based CFT did not emerge as an efficacious treatment for PGS. Possible explanations include that CFT may not target core maintaining processes in PGS and that the group-based, 8-week operationalization of CFT may be less than optimal.