In Schizophrenia, Chronic Fatigue Syndrome- and Fibromyalgia-Like Symptoms are Driven by Breakdown of the Paracellular Pathway with Increased Zonulin and Immune Activation-Associated Neurotoxicity.

BACKGROUND: A meaningful part of schizophrenia patients suffer from physiosomatic symptoms (formerly named psychosomatic), which are reminiscent of chronic fatigue syndrome and fibromyalgia (FF) and are associated with signs of immune activation and increased levels of tryptophan catabolites (TRYCATs). AIMS: The study aims to examine whether FF symptoms in schizophrenia are associated with the breakdown of the paracellular pathway, zonulin, lowered natural IgM responses to oxidative specific epitopes (OSEs); and whether FF symptoms belong to the behavioral-cognitive-physical-psychosocial- (BCPS)-worsening index consisting of indices of a general cognitive decline (G-CoDe), symptomatome of schizophrenia, and quality of life (QoL)-phenomenome. METHODS: FF symptoms were assessed using the Fibromyalgia and Chronic Fatigue Rating scale in 80 schizophrenia patients and 40 healthy controls and serum cytokines/chemokines, IgA levels to TRYCATs, IgM to OSEs, zonulin and transcellular/paracellular (TRANS/PARA) molecules were assayed using ELISA methods. RESULTS: A large part (42.3%) of the variance in the total FF score was explained by the regression on the PARA/TRANS ratio, pro-inflammatory cytokines, IgM to zonulin, IgA to TRYCATs (all positively), and IgM to OSEs (inversely). There were highly significant correlations between the total FF score and G-CoDe, symtopmatome, QoL phenomenome, and BCPS-worsening score. FF symptoms belong to a common core shared by G-CoDe, symtopmatome, and QoL phenomenome. CONCLUSION: The physio-somatic symptoms of schizophrenia are driven by various pathways, including increased zonulin, breakdown of the paracellular tight-junctions pathway, immune activation with induction of the TRYCAT pathway, and consequent neurotoxicity. It is concluded that FF symptoms are part of the phenome of schizophrenia and BCPS-worsening as well.

Do humor styles predict clinical response to the MINDSET (MINDfulneSs & EducaTion) program? A pilot study in patients with fibromyalgia / ¿Los estilos de humor predicen la respuesta clínica al programa MINDSET (MINDfulneSs & EducaTion)? Un estudio piloto en pacientes con fibromialgia

Background and aim: Humor has been described as an effective coping strategy for dealing with chronic pain conditions; likewise, coping strategies predict some clinical outcomes after cognitive-behavioral therapy and mindfulness-based interventions. The present study aims to preliminarily explore the role of humor styles in predicting clinical changes after the multicomponent intervention (MINDSET) that combines mindfulness and psychoeducation for fibromyalgia (FM) patients. Material and methods: A subsample of 35 patients with FM of the EUDAIMON study, a randomized controlled trial, was used for the present study; linear regressions and Spearman's correlations were computed. Results: Affiliative humor and positive/negative ratio humor styles had a unique predictive effect on self-reported clinical changes. Significant correlations between humor styles with functional impact and mindfulness facets were observed. Conclusions: Some humor styles may imply a better disposition in patients to learn and implement the concepts and resources that the intervention offered.(AU)

Antecedentes y objetivo: El humor se considera una estrategia de afrontamiento efectiva para afrontar enfermedades crónicas; asimismo, las estrategias de afrontamiento pueden predecir cambios clínicos experimentados tras intervenciones cognitivo-conductuales y basadas en mindfulness. El presente estudio explora el rol de los estilos de humor en la predicción de cambios clínicos tras una intervención multicomponente (MINDSET, mindfulness+psicoeducación) para pacientes con fibromialgia. Materiales y métodos: En este estudio participaron 35 pacientes con fibromialgia, una submuestra del ensayo controlado y aleatorizado del estudio EUDAIMON. Se realizaron regresiones lineales y correlaciones de Spearman. Resultados: El humor afiliativo y la ratio de estilos positivos/negativos mostraron un efecto predictor en cambios clínicos auto-reportados. Se observaron correlaciones significativas entre estilos de humor, impacto funcional y facetas de mindfulness. Conclusiones: Algunos estilos de humor pueden implicar una mejor predisposición en los pacientes para aprender y aplicar los recursos que la intervención ofrece.(AU)

Do humor styles predict clinical response to the MINDSET (MINDfulneSs & EducaTion) program? A pilot study in patients with fibromyalgia.

BACKGROUND AND AIM: Humor has been described as an effective coping strategy for dealing with chronic pain conditions; likewise, coping strategies predict some clinical outcomes after cognitive-behavioral therapy and mindfulness-based interventions. The present study aims to preliminarily explore the role of humor styles in predicting clinical changes after the multicomponent intervention (MINDSET) that combines mindfulness and psychoeducation for fibromyalgia (FM) patients. MATERIAL AND METHODS: A subsample of 35 patients with FM of the EUDAIMON study, a randomized controlled trial, was used for the present study; linear regressions and Spearman's correlations were computed. RESULTS: Affiliative humor and positive/negative ratio humor styles had a unique predictive effect on self-reported clinical changes. Significant correlations between humor styles with functional impact and mindfulness facets were observed. CONCLUSIONS: Some humor styles may imply a better disposition in patients to learn and implement the concepts and resources that the intervention offered.

Efficacy, cost-utility and physiological effects of Acceptance and Commitment Therapy (ACT) and Behavioural Activation Treatment for Depression (BATD) in patients with chronic low back pain and depression: study protocol of a randomised, controlled trial including mobile-technology-based ecological momentary assessment (IMPACT study).

INTRODUCTION: The IMPACT study focuses on chronic low back pain (CLBP) and depression symptoms, a prevalent and complex problem that represents a challenge for health professionals. Acceptance and Commitment Therapy (ACT) and Brief Behavioural Activation Treatment for Depression (BATD) are effective treatments for patients with persistent pain and depression, respectively. The objectives of this 12 month, multicentre, randomised, controlled trial (RCT) are (i) to examine the efficacy and cost-utility of adding a group-based form of ACT or BATD to treatment-as-usual (TAU) for patients with CLBP and moderate to severe levels of depressive symptoms; (ii) identify pre-post differences in levels of some physiological variables and (iii) analyse the role of polymorphisms in the FKBP5 gene, psychological process measures and physiological variables as mediators or moderators of long-term clinical changes. METHODS AND ANALYSIS: Participants will be 225 patients with CLBP and moderate to severe depression symptoms recruited at Parc Sanitari Sant Joan de Déu (St. Boi de Llobregat, Spain) and Hospital del Mar (Barcelona, Spain), randomly allocated to one of the three study arms: TAU vs TAU+ACT versus TAU+BATD. A comprehensive assessment to collect clinical variables and costs will be conducted pretreatment, post-treatment and at 12 months follow-up, being pain interference the primary outcome measure. The following physiological variables will be considered at pretreatment and post-treatment assessments in 50% of the sample: immune-inflammatory markers, hair cortisol and cortisone, serum cortisol, corticosteroid-binding globulin and vitamin D. Polymorphisms in the FKBP5 gene (rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916) will be analysed at baseline assessment. Moreover, we will include mobile-technology-based ecological momentary assessment, through the Pain Monitor app, to track ongoing clinical status during ACT and BATD treatments. Linear mixed-effects models using restricted maximum likelihood, and a full economic evaluation applying bootstrapping techniques, acceptability curves and sensitivity analyses will be computed. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the Fundació Sant Joan de Déu and Hospital del Mar. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media and various community engagement activities. TRIAL REGISTRATION NUMBER: NCT04140838.

The Bed Nucleus of the Stria Terminalis as a Brain Correlate of Psychological Inflexibility in Fibromyalgia.

This study explored the brain structural correlates of psychological flexibility (PF) as measured with the Psychological Inflexibility in Pain Scale (PIPS) in patients with fibromyalgia (FM). Structural magnetic resonance imaging data from 47 FM patients were used to identify Gray Matter Volume (GMV) alterations related to PIPS scores. Brain GMV clusters related to PIPS were then correlated with clinical and cognitive variables to further explore how emerged brain clusters were intertwined with FM symptomatology. Longitudinal changes in PIPS-related brain clusters values were assessed by studying pre-post data from 30 patients (15 allocated to a mindfulness-based stress reduction (MBSR) program and 15 to treatment-as-usual). Changes in PIPS-related brain clusters were also explored in participants showing greater/lower longitudinal changes in PIPS scores. PIPS scores were positively associated with GMV in a bilateral cluster in the ventral part of the bed nucleus of the stria terminalis (BNST). Significant associations between BNST cluster with functional impairment, depressive symptomatology, perceived stress and the nonjudging mindfulness facet were observed. Participants reporting greater pre-post increases in PIPS scores showed greater increases in BNST cluster values. These findings contribute to the understanding on the neurobiological bases of PF in FM and encourage further explorations of the role of the BNST in chronic pain.

Peripheral immune aberrations in fibromyalgia: A systematic review, meta-analysis and meta-regression.

The objective was to identify immune alterations in patients with fibromyalgia syndrome (FMS) compared to healthy controls (HC) using meta-analysis and meta-regression. Six electronic databases were searched for suitable original articles investigating immune biomarkers in FMS in comparison to HC. We extracted outcomes and variables of interest, such as mean and SD of peripheral blood immune biomarkers, age or sex. A random-effects model with restricted maximum-likelihood estimator was used to compute effect sizes (standardized mean difference and 95% CI, Hedges' g) and meta-analysis, group meta-analysis and meta-regressions were conducted. Forty-three papers were included in this systematic review, of which 29 were suitable for meta-analysis. Interleukin (IL)-6 (g = 0.36 (0.09-0.63); I2 = 85.94; p = 0.01), IL-4 (g = 0.50 (0.03-0.98); I2 = 81.87; p = 0.04), and IL-17A (g = 0.53 (0.00-1.06); I2 = 87.15; p = 0.05), were significantly higher in FMS compared to HC while also combinations of cytokines into relevant phenotypes were significantly upregulated including M1 macrophage (g = 0.23 (0.03-0.43); I2 = 77.62; p = 0.02), and immune-regulatory (g = 0.40 (0.09-0.72); I2 = 84.81; p = 0.01) phenotypes. Heterogeneity levels were very high and subgroup and meta-regression analyses showed that many covariates explained part of the heterogeneity including medication washout, sex, time of blood sampling and exclusion of patients with major depressive disorder. In conclusion, FMS is accompanied by a disbalance between upregulated pro-inflammatory (M1 and Th-17) and immune-regulatory cytokines although effect sizes are small-to-moderate. Based on our results we provide specific methodological suggestions for future research, which should assess Th-1, Th-17, chemokines, and Th-2 phenotypes while controlling for possible confounding variables specified in this study.

Patients With Fibromyalgia Reporting Severe Pain but Low Impact of the Syndrome: Clinical and Pain-Related Cognitive Features.

BACKGROUND: Fibromyalgia (FM) is a prevalent and highly disabling chronic pain syndrome. However, differences among patients regarding how pain impacts on daily life are remarkable. The main aim of this study was to identify clinical and pain-related cognitive variables characterizing patients reporting high adaptability despite experiencing severe chronic pain. METHODS: Two hundred and eighty-three Spanish patients with FM with high levels of pain were classified into 2 groups: (1) those reporting low impact of the syndrome, and (2) those with moderate-to-high impact. Perceived stress, anxiety, and depressive symptoms along with pain catastrophizing, psychological inflexibility, and perceived control over pain were evaluated. Differences in sociodemographics, years with FM, past/current major depressive disorder comorbidity, and health-related economic costs (ie, medications, use of medical services, lost productivity due to sick leave) were also assessed. Stepwise logistic regression analyses predicting group membership from clinical variables and pain-related cognitive processes as predictors were performed. RESULTS: Lower stress, anxiety, and depressive symptoms, along with reduced pain catastrophism, psychological inflexibility, and perceived control over pain, were found in the low-impact group. Significant predictors of group membership (low-impact vs. moderate-to-high impact) in regression analyses were "cognitive fusion" (psychological inflexibility), "helplessness" (pain catastrophizing), and depressive symptomatology, together with pain intensity and other FM symptoms. CONCLUSIONS: The present study provides further evidence on resilience resources in chronic pain by identifying some variables (ie, reduced depressive symptomatology, pain catastrophizing, and psychological inflexibility) differentially characterizing a profile of patients with FM who are especially able to adapt to high levels of pain.

Effects of attachment-based compassion therapy (ABCT) on brain-derived neurotrophic factor and low-grade inflammation among fibromyalgia patients: A randomized controlled trial.

Fibromyalgia (FM) is a disabling syndrome characterized by chronic pain associated with fatigue. Its pathogenesis is unknown, but alterations in central sensitization, involving an imbalance of brain-derived neurotrophic factor (BDNF) and inflammatory biomarkers, appear to be implicated. The aim of this study was to evaluate the impact of attachment-based compassion therapy (ABCT) on levels of BDNF, the inflammatory markers TNF-α, IL-6, IL-10, and the C-reactive protein (CRP), analysing whether biomarkers play a mediating/moderating role in improvements in FM functional status. Thirty-four female patients with FM participated in a RCT and were assigned to ABCT or relaxation therapy. Blood extractions were conducted at baseline and post-intervention, with self-report assessments of functional status (FIQ) at baseline, post-intervention and 3-month follow-up. A pro-inflammatory composite was obtained by summing up IL-6, TNF-α and CRP normalized values. Non-parametric tests, analysis of variance and regression models were used to evaluate treatment and mediation/moderation. Compared to relaxation therapy, ABCT showed significant improvements in FIQ and decreases in BDNF, CRP, and pro-inflammatory composite. Changes in BDNF had a mediating role in FIQ. ABCT seems to reduce BDNF and appears to have anti-inflammatory effects in FM patients. Reductions in BDNF could be a mechanism of FM functional status improvement.Clinical Trial Registration: http://ClinicalTrials.gov , identifier NCT02454244. Date: May 27th, 2015.

Machine Learning to Understand the Immune-Inflammatory Pathways in Fibromyalgia.

Fibromyalgia (FM) is a chronic syndrome characterized by widespread musculoskeletal pain, and physical and emotional symptoms. Although its pathophysiology is largely unknown, immune-inflammatory pathways may be involved. We examined serum interleukin (IL)-6, high sensitivity C-reactive protein (hs-CRP), CXCL-8, and IL-10 in 67 female FM patients and 35 healthy women while adjusting for age, body mass index (BMI), and comorbid disorders. We scored the Fibromyalgia Severity Score, Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Hospital Anxiety (HADS-A), and Depression Scale and the Perceived Stress Scale (PSS-10). Clinical rating scales were significantly higher in FM patients than in controls. After adjusting for covariates, IL-6, IL-10, and CXCL-8 were lower in FM than in HC, whereas hs-CRP did not show any difference. Binary regression analyses showed that the diagnosis FM was associated with lowered IL-10, quality of sleep, aerobic activities, and increased HADS-A and comorbidities. Neural networks showed that WPI was best predicted by quality of sleep, PSS-10, HADS-A, and the cytokines, while SSS was best predicted by PSS-10, HADS-A, and IL-10. Lowered levels of cytokines are associated with FM independently from confounders. Lowered IL-6 and IL-10 signaling may play a role in the pathophysiology of FM.

Fifteen Years Controlling Unwanted Thoughts: A Systematic Review of the Thought Control Ability Questionnaire (TCAQ).

Thought control ability is a vulnerability factor implicated in the etiology and maintenance of emotional disorders. This manuscript aims to systematically review the use and psychometric performance of the Thought Control Ability Questionnaire (TCAQ), designed to assess people's ability to control unwanted thoughts. Three electronic databases were searched for papers administering the TCAQ published in indexed peer-reviewed journals. Data (participants characteristics, country, study design, etc.) were extracted from the results for qualitative synthesis. The TCAQ's content validity, dimensionality, internal consistency, test-retest reliability, convergent/divergent validity, floor/ceiling effects, and interpretability were summarized. Two reviewers independently screened articles and assessed quality taking COSMIN criteria into account. Finally, the review included 17 papers. The TCAQ has been administered to healthy individuals, students, and adult patients, in six languages from nine countries. We found that the TCAQ, and its shorter versions, demonstrate robust reliability and adequate content validity. Of interest is the TCAQ's capacity to predict performance in diverse experimental tasks focused on thought control. The TCAQ unidimensionality has been supported in exploratory and confirmatory factor analyses. Regarding construct validity, the TCAQ is significantly related to a wide range of psychopathological measures of anxiety, worry, depression, obsessive-compulsive symptoms, etc. However, as only a few of the included studies had a longitudinal design, we are unable to draw firm conclusions about the measure's temporal stability. Moreover, psychometric aspects such as factorial invariance across different samples have not been analyzed. Despite these limitations, based on available psychometric evidence we can recommend using the TCAQ for measuring perceived control of unwanted thoughts.

Cost-Utility of Mindfulness-Based Stress Reduction for Fibromyalgia versus a Multicomponent Intervention and Usual Care: A 12-Month Randomized Controlled Trial (EUDAIMON Study).

Fibromyalgia (FM) is a prevalent, chronic, disabling, pain syndrome that implies high healthcare costs. Economic evaluations of potentially effective treatments for FM are needed. The aim of this study was to analyze the cost-utility of Mindfulness-Based Stress Reduction (MBSR) as an add-on to treatment-as-usual (TAU) for patients with FM compared to an adjuvant multicomponent intervention ("FibroQoL") and to TAU. We performed an economic evaluation alongside a 12 month, randomized, controlled trial; data from 204 (68 per study arm) of the 225 patients (90.1%) were included in the cost-utility analyses, which were conducted both under the government and the public healthcare system perspectives. The main outcome measures were the EuroQol (EQ-5D-5L) for assessing Quality-Adjusted Life Years (QALYs) and improvements in health-related quality of life, and the Client Service Receipt Inventory (CSRI) for estimating direct and indirect costs. Incremental cost-effectiveness ratios (ICERs) were also calculated. Two sensitivity analyses (intention-to-treat, ITT, and per protocol, PPA) were conducted. The results indicated that MBSR achieved a significant reduction in costs compared to the other study arms (p < 0.05 in the completers sample), especially in terms of indirect costs and primary healthcare services. It also produced a significant incremental effect compared to TAU in the ITT sample (ΔQALYs = 0.053, p < 0.05, where QALYs represents quality-adjusted life years). Overall, our findings support the efficiency of MBSR over FibroQoL and TAU specifically within a Spanish public healthcare context.

A randomized controlled efficacy trial of mindfulness-based stress reduction compared with an active control group and usual care for fibromyalgia: the EUDAIMON study.

Fibromyalgia (FM) syndrome represents a great challenge for clinicians and researchers because the efficacy of currently available treatments is limited. This study examined the efficacy of mindfulness-based stress reduction (MBSR) for reducing functional impairment as well as the role of mindfulness-related constructs as mediators of treatment outcomes for people with FM. Two hundred twenty-five participants with FM were randomized into 3 study arms: MBSR plus treatment-as-usual (TAU), FibroQoL (multicomponent intervention for FM) plus TAU, and TAU alone. The primary endpoint was functional impact (measured with the Fibromyalgia Impact Questionnaire Revised), and secondary outcomes included "fibromyalginess," anxiety and depression, pain catastrophising, perceived stress, and cognitive dysfunction. The differences in outcomes between groups at post-treatment assessment (primary endpoint) and 12-month follow-up were analyzed using linear mixed-effects models and mediational models through path analyses. Mindfulness-based stress reduction was superior to TAU both at post-treatment (large effect sizes) and at follow-up (medium to large effect sizes), and MBSR was also superior to FibroQoL post-treatment (medium to large effect sizes), but in the long term, it was only modestly better (significant differences only in pain catastrophising and fibromyalginess). Immediately post-treatment, the number needed to treat for 20% improvement in MBSR vs TAU and FibroQoL was 4.0 (95% confidence interval [CI] = 2.1-6.5) and 5.0 (95% CI = 2.7-37.3). An unreliable number needed to treat value of 9 (not computable 95% CI) was found for FibroQoL vs TAU. Changes produced by MBSR in functional impact were mediated by psychological inflexibility and the mindfulness facet acting with awareness. These findings are discussed in relation to previous studies of psychological treatments for FM.

Immune-inflammatory pathways and clinical changes in fibromyalgia patients treated with Mindfulness-Based Stress Reduction (MBSR): A randomized, controlled clinical trial.

Fibromyalgia (FM) is a highly prevalent and disabling syndrome characterized by chronic widespread musculoskeletal pain and a broad range of cognitive and affective symptoms. Up to now, the pathogenesis of FM is unknown although a peripheral and central sensitization involving an imbalance on immune biomarkers appears to have a relevant role in its aetiology. The aim of this study was to extend previous clinical findings of Mindfulness-Based Stress Reduction (MBSR) to both its impact on clinical symptomatology and immune biomarkers (IL-6, CXCL8, IL-10 and hs-CRP), and also to explore the role of biomarkers as predictors of efficacy. METHODS: A total of 70 female patients with FM were randomly assigned to two treatment modalities, namely Treatment as Usual (TAU) plus MBSR (n = 35) or TAU alone (n = 35). This study is embedded within a larger RCT (n = 225) that includes three study arms (TAU; TAU plus MBSR; and TAU plus the psychoeducative intervention FibroQoL), and a 12-month follow-up (clinical trial registration: NCT02561416). Blood cytokine assays and clinical assessment were conducted at baseline and post-treatment. Treatment effects were analysed using linear mixed models with intention to treat and per protocol analyses. In order to evaluate the balance between pro- and anti-inflammatory pathways, ratios of pro-inflammatory IL-6, CXCL8 and hs-CRP with the anti-inflammatory cytokine IL-10 were calculated (i.e. IL-6/IL-10, CXCL8/IL10 and hs-CRP/IL-10). RESULTS: The results show that MBSR is an efficacious intervention to reduce clinical severity of patients with FM. MBSR also prevents the tendency of IL-10 to decrease as observed in the TAU group. Higher levels of baseline CXCL8 levels attenuate the beneficial effect of MBSR practice on clinical symptomatology, including pain, energy, stiffness or quality of sleep. Furthermore, higher baseline IL-6/IL-10 and CXCL8/IL-10 ratios were associated with less improvement in psychological inflexibility following MBSR treatment. DISCUSSION: Our results show that mindfulness training has clinical efficacy in patients with FM. The results suggest that MBSR has significant immune regulatory effects in FM patients, while immune-inflammatory pathways may in part predict the clinical efficacy of MBSR. These cytokines and chemokines may be adequate biomarkers to monitor responsivity to MBSR.

Laughing away the pain: A narrative review of humour, sense of humour and pain.

BACKGROUND AND OBJECTIVE: The link between humour and sense of humour with pain has been a topic of research for decades. The purpose of the present article was to review the different studies that have been conducted to date on the association between humour and sense of humour with pain. DATABASES AND DATA TREATMENT: The literature search was conducted using the PubMed, Science Direct and ProQuest databases. Forty-one studies were reviewed, and the results are summarized and structured into three sections: experimental pain, chronic pain and pain in children. RESULTS: For experimental pain, the findings support the idea that humorous distractions, such as watching a comedy clip, increase pain tolerance, although most of the studies indicate that other non-humorous distractions produce similar effects. Regarding chronic pain, humour has been studied as a way of coping with pain and the emotional distress produced by chronic pain conditions. The results of correlational studies show significant associations between the use of humour and main variables such as anxiety and catastrophizing. Finally, concerning pain in children, similar findings to those described for the previous sections have been reported, with a notable presence of studies on clinic clown interventions, which promote emotional well-being among children and their parents, although their effectiveness in pain reduction is controversial. CONCLUSIONS: The study of the link between humour and pain is still on an early stage, and overcoming the limitations of previous studies is required to strengthen the promising results that have been observed up to date. SIGNIFICANCE: This review summarizes all main findings regarding humour, sense of humour and pain up until the first half of 2018 and offers a list of aspects to be considered in further studies regarding the link of humour and pain to contribute to a more systematic research.

Clustering a large Spanish sample of patients with fibromyalgia using the Fibromyalgia Impact Questionnaire-Revised: differences in clinical outcomes, economic costs, inflammatory markers, and gray matter volumes.

The main objective of this study is to identify fibromyalgia syndrome (FMS) clusters using the Revised Fibromyalgia Impact Questionnaire (FIQR), and to examine whether the clusters differ in sociodemographic characteristics, clinical measures, direct and indirect costs, levels of inflammatory markers, and brain morphometry. A hierarchical cluster analysis was performed to classify a large, pooled Spanish sample of patients with FMS (N = 947) using the FIQR as clustering variable. A latent profile analysis was subsequently conducted to confirm the optimal number of FMS clusters. To examine external validity, a battery of clinical measures, economic costs, inflammatory markers, and gray matter volumes of relevant cortical and subcortical areas were analyzed. We also compared the discriminant validity of the clusters with the original FIQR severity categories. To promote the implementation in real-world clinical practice, we built a free online cluster calculator. Our findings indicated that a four-cluster solution more clearly captured the heterogeneity of FIQR data and provided the best fit. This cluster solution allowed for detection of differences for most clinical outcomes and economic costs. Regarding the inflammatory and brain-based biomarkers, differences were found in C-reactive protein, and tendencies were found in the right medial prefrontal cortex, the right parahippocampal gyrus, and the right middle cingulate cortex; brain regions associated with executive functions and pain processing. The original FIQR categories presented similar results, although their precision in discriminating among the nonextreme categories (ie, moderate and severe) was not sound. These findings are discussed in relation to previous research on FMS clustering.

Economic Impact of Third-Wave Cognitive Behavioral Therapies: A Systematic Review and Quality Assessment of Economic Evaluations in Randomized Controlled Trials.

The term third-wave cognitive behavioral therapy (CBT) encompasses new forms of CBT that both extend and innovate within CBT. Most third-wave therapies have been subject to randomized controlled trials (RCTs) focused on clinical effectiveness; however, the number and quality of economic evaluations in these RCTs has been unknown and may be few. Evidence about efficiency of these therapies may help support decisions on efficient allocation of resources in health policies. The main aim of this study was to systematically review the economic impact of third-wave therapies in the treatment of patients with physical or mental conditions. We conducted a systematic literature search in PubMed, PsycINFO, EMBASE, and CINALH to identify economic evaluations of third-wave therapies. Quality and Risk of Bias (RoB) assessment of economic evaluations was also made using the Drummond 35-item checklist and the Cochrane Collaboration's tool for assessing risk of bias, respectively. Eleven RCTs were included in this systematic review. Mindfulness-Based Cognitive Therapy (MBCT), Mindfulness-Based Stress Reduction (MBSR), Acceptance and Commitment Therapy (ACT), Dialectical Behavior Therapy (DBT), and extended Behaviour Activation (eBA) showed acceptable cost-effectiveness and cost-utility ratios. No study employed a time horizon of more than 3 years. Quality and RoB assessments highlight some limitations that temper the findings. There is some evidence that MBCT, MBSR, ACT, DBT, and eBA are efficient from a societal or a third-party payer perspective. No economic analysis was found for many third-wave therapies. Therefore, more economic evaluations with high methodological quality are needed.

Effectiveness of the "What's Up!" Intervention to Reduce Stigma and Psychometric Properties of the Youth Program Questionnaire (YPQ): Results from a Cluster Non-randomized Controlled Trial Conducted in Catalan High Schools.

Mental disorders are highly prevalent in the general population, and people who experience them are frequently stigmatized. Stigma has a very negative impact on social, academic/professional, and personal life. Considering the high rates of mental disorders among children and adolescents (13.4%) and how critical this age is in the formation of nuclear beliefs, many campaigns to combat stigma have been developed in the last decade, with mixed results. The OBERTAMENT initiative has produced various anti-stigma campaigns in Catalonia (Spain). In the present study, the main objective was to report on the effectiveness of the OBERTAMENT "What's up!" intervention, a curricular intervention including education and social contact conducted by the teachers in the classroom with teenagers aged between 14 and 18. Prior to this, we examined the psychometric properties of the Youth Program Questionnaire (YPQ), our main outcome measure, in terms of dimensionality, reliability, and validity. A cluster non-randomized controlled trial was conducted to assess this intervention, which was tested in nine high schools situated in the Barcelona region. A convenience sample of 261 students formed the intervention group and 132 the control group (52% women, mean age = 14, SD = 0.47). The assignment to study conditions was conducted by Departament d'Ensenyament (Department of Education), Generalitat de Catalunya (Catalan Government). Participants were evaluated at baseline, post-intervention, and 9-month follow-up. The main outcome measure of this study was the YPQ. The Reported and Intended Behavior Scale (RIBS) was used as secondary outcome measure. The statistical analysis indicated that the YPQ possesses a two-factor structure (stereotypical attitudes and intended behavior) and sound psychometric properties. The multilevel mixed-effects models revealed statistically significant interactions for both study measures and post hoc intragroup analyses revealed a significant but small improvement in the YPQ and RIBS scores in the intervention group. Overall, our results indicate that "What's up!" produced statistically significant, albeit small improvements in stereotypical attributions and intended behavior toward people with mental disorders. Some methodological limitations and the relatively low levels of stigma observed in our sample may undermine our results. The implications of our results are discussed in relation to stigma research.

Psychometric Properties of the Cognitive Emotion Regulation Questionnaire (CERQ) in Patients with Fibromyalgia Syndrome.

Given that Fibromyalgia Syndrome (FMS) is associated with problems in emotion regulation, the importance of assessing this construct is widely acknowledged by clinical psychologists and pain specialists. Although the Cognitive Emotion Regulation Questionnaire (CERQ) is a self-report measure used worldwide, there are no data on its psychometric properties in patients with FMS. This study analyzed the dimensionality, reliability, and validity of the CERQ in a sample of 231 patients with FMS. Given that "fibrofog" is one of the most disabling FMS symptoms, in the present study, items in the CERQ were grouped by dimension. This change in item presentation was conceived as an efficient way of facilitating responses as a result of a clear understanding of what the items related to each dimension are attempting to measure. The following battery of measures was administered: the CERQ, the Revised Fibromyalgia Impact Questionnaire, the Pain Catastrophizing Scale, the Center for Epidemiologic Studies Depression Scale, and the State-Trait Anxiety Inventory. Four models of the CERQ structure were examined and confirmatory factor analyses supported the original factor model, consisting of nine factors-Self-blame, Acceptance, Rumination, Positive refocusing, Refocus on planning, Positive reappraisal, Putting into perspective, Catastrophizing, and Other-blame. There was minimal overlap between CERQ subscales and their internal consistency was adequate. Correlational and regression analyses supported the construct validity of the CERQ. Our findings indicate that the CERQ (items-grouped version) is a sound instrument for assessing cognitive emotion regulation in patients with FMS.