Inflammatory Markers in Children and Adolescents with Functional Somatic Disorders: A Systematic Review.

Functional somatic disorders (FSDs) are common in children and adolescents. Recent findings suggest that low-grade inflammation has a role in the development and maintenance of pediatric FSDs. This systematic review included studies with original data on systemic inflammatory markers in children and adolescents with an FSD compared to individuals without an FSD. The literature search identified 1374 articles. After assessment, a total of 15 studies met the inclusion criteria. In total, 41 serum or plasma cytokines were assayed in a population of 696 children and adolescents. Altered cytokine levels in patients with FSDs were reported in 12 studies, whereas three studies found no significant differences when comparing patients with FSDs and controls. The cytokine levels were significantly elevated in nine studies (i.e., IL-2, IL-6, IL-8, IL-12 (p70), CRP, hsCRP, IP-10, MCP-1, sTIM-3, sCD25 and TNF-α). The findings indicate that inflammatory response may have a role in the pathophysiology of pediatric FSDs. However, the included studies showed limited quality with potential risk of bias, small study populations and a narrow spectrum of included FSDs, which limits the generalizability of the results. To further explore the potential link between inflammatory markers and pediatric FSDs, future research using a longitudinal study design is recommended.

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.

A New Experimental Design to Examine Cognitive Biases for Gastrointestinal Related Stimuli in Children and Adolescents.

Cognitive biases toward disorder-specific stimuli are suggested as crucial to the development and maintenance of symptoms in adults with functional gastrointestinal disorders (FGID). Functional abdominal pain disorders (FAPD), a subtype of FGID, are common in children and adolescents, but the influence of cognitive biases is sparsely examined. This study aimed to (1) develop a new experimental design for assessing cognitive biases toward gastrointestinal stimuli in children and adolescents (aged 8 to 17 years) and (2) derive comparative data on bias toward gastrointestinal stimuli using a healthy "normative" sample. The online experimental design-BY-GIS (Bias in Youth toward GastroIntestinal-related Stimuli)-includes a word task and a picture task. Stimuli in both tasks are related to general and gastrointestinal symptoms, and the design includes three phases: (1) encoding, (2) free recall, and (3) recognition. Data were collected between April 2022 and April 2023 from 96 healthy participants (Mage = 12.32, 47.92% female). Adolescents were significantly better at recalling words than children (p = 0.03), whereas there were no significant gender or age differences with regard to recalling pictures (p > 0.05). Across age and gender, participants performed above chance level in the recognition phases of both tasks. The results support that the design is suitable within the age span.

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.

Group-based Acceptance and Commitment Therapy (AHEAD) for adolescents with multiple functional somatic syndromes: A randomised trial.

Background: Evidence for treatment of adolescents with multiple functional somatic syndromes (FSS) is sparse. This study examined the efficacy of 'Acceptance and Commitment Therapy for Health in Adolescents' (AHEAD), a generic group-based treatment for adolescents with co-occurrence of multiple FSS. Methods: A randomized trial was conducted at a specialized university hospital clinic. Adolescents (15-19 years) with multiple FSS of at least 1 year's duration were randomly assigned to AHEAD or enhanced usual care (EUC). AHEAD consisted of nine modules (i.e., 27 h) and one follow-up meeting. Primary outcome was physical health (SF-36). Various secondary outcomes and treatment targets were included (e.g., symptom severity, symptom impact, and illness perception). A linear mixed-effects model was used for analysis. Trial-registration: ClinicalTrials.gov NCT02346071. Results: Ninety-one patients were included. At 12 months, no significant difference in physical health was identified between groups (mean adjusted difference 1.2 [95% CI -1.6 to 4.0], p = .404). However, different developments over time were seen with an interaction effect between intervention arm and time (χ2(5) = 14.1, p = .0148). AHEAD patients (n = 44) reported a clinically relevant improvement at end of treatment and at 8 and 12 months, while EUC patients (n = 47) displayed a clinically relevant improvement at 12 months. Furthermore, AHEAD patients showed a faster improvement on symptom severity, symptom impact and illness perception. EUC patients received more psychological treatment outside the trial (p ≤ .001) than AHEAD patients. Treatment satisfaction with AHEAD was high in contrast to EUC. Conclusions: Compared with EUC, AHEAD had no additional advantage on the improvement of physical health at the primary endpoint of 12 months. However, a faster improvement of physical health was seen in AHEAD and considerably more psychological treatment was received outside the trial in EUC with clinically meaningful improvements in both groups. The results underpin the importance of an organised and systematic treatment offer for the most severely affected youth.

Feasibility of group-based acceptance and commitment therapy for adolescents (AHEAD) with multiple functional somatic syndromes: a pilot study.

BACKGROUND: Recurrent and impairing functional somatic syndromes (FSS) are common in adolescents. Despite a high need for care, empirically supported treatments are lacking for youth. The aim of this uncontrolled pilot study was to assess feasibility and treatment potential of a new intervention with group-based Acceptance and Commitment Therapy (ACT) in a generic treatment approach for adolescents with multiple FSS. METHODS: Twenty-one patients received 'ACT for Health in Adolescents' (AHEAD) (30 h), specifically developed for adolescents (aged 15-19 years) with moderate to severe FSS. Close relatives attended an information meeting to facilitate support of the patients throughout treatment. Treatment satisfaction was evaluated by means of self-report and relatives' impressions. Self-reported physical health at 3 months follow-up (FU) after end of treatment was the primary outcome whereas secondary outcomes included symptom burden, limitation due to symptoms, illness worry, emotional distress and physical and emotional symptoms. Treatment targets were assessed by measures on illness behaviour, illness perception and psychological inflexibility. RESULTS: Nineteen patients (90.5%) completed the treatment with a high overall attendance rate of 93%. All would recommend the treatment to a friend with similar problems. Close relatives rated it valuable to participate in an information meeting. Patients' physical health improved significantly from assessment to FU with a clinically relevant mean change of 8.9 points (95% CI [5.4; 12.4]; SRM 0.91 [0.26;1.57]). Improvement was also seen on all secondary outcome measures, from assessment to FU. Maladaptive illness behaviours and perceptions as well as psychological inflexibility showed a significant decline from assessment to FU. CONCLUSION: AHEAD was feasible and potentially efficacious and warrants testing in a larger clinical trial. TRIAL REGISTRATION: Clinical Trials gov NCT04464447 , registration date July 9th, 2020. Retrospectively registered.

Comparing group-based acceptance and commitment therapy (ACT) with enhanced usual care for adolescents with functional somatic syndromes: a study protocol for a randomised trial.

INTRODUCTION: Functional somatic syndromes (FSS) are common in adolescents, characterised by severe disability and reduced quality of life. Behavioural treatments such as acceptance and commitment therapy (ACT) has shown promising results in children and adolescents with FSS, but has focused on specific syndromes such as functional pain. The current study will compare the efficacy of group-based ACT with that of enhanced usual care (EUC) in adolescents with a range of FSS operationalised by the unifying construct of multiorgan bodily distress syndrome (BDS). METHODS AND ANALYSIS: A total of 120 adolescents aged 15-19 and diagnosed with multiorgan BDS, of at least 12 months duration, will be assessed and randomised to either: (1) EUC: a manualised consultation with a child and adolescent psychiatrist and individualised treatment plan or (2) manualised ACT-based group therapy plus EUC. The ACT programme consists of 9 modules (ie, 27 hours) and 1 follow-up meeting (3 hours). The primary outcome is physical health, assessed by an Short Form Health Survey (SF-36) aggregate score 12 months after randomisation. Secondary outcomes include self-reported symptom severity, symptom interference, depression and anxiety, illness worry, perceived stress and global improvement; as well as objective physical activity and bodily stress response measured by heart rate variability, hair cortisol and inflammatory biomarkers. Process measures are illness perception, illness-related behaviour and psychological flexibility. ETHICS AND DISSEMINATION: The study is conducted in accordance with Helsinki Declaration II. Approval has been obtained from the Science Ethics Committee of the Central Denmark Region and the Danish Data Protection. The results will be sought to be published according to the CONSORT statement in peer-reviewed journals. DISCUSSION: This is one of the first larger randomised clinical trials evaluating the effect of a group-based intervention for adolescents with a range of severe FSS. TRIAL REGISTRATION NUMBER: NCT02346071; Pre-results.

[Possible side effects from HPV vaccination in Denmark].

HPV vaccination offers protection against ~70% of cervical cancers, however, serious concerns have been raised about the possible side effects from HPV vaccination. Studies have found no increased risk of neurologic disease, autoimmune disorder, thromboembolic disease, postural orthostatic tachycardia syndrome, or complex regional pain syndrome in HPV-vaccinated persons compared to unvaccinated persons. Affected individuals should undergo a proper clinical examination to ensure a correct diagnosis and treatment, because symptoms might arise due to a somatic, psychiatric or functional disorder.