Journal of Psychosomatic Research

ABSTRACT Purpose: Survivors of severe COVID-19 commonly experience post-intensive care syndrome (PICS), which includes depression and fatigue. Fatigue is far more common and may inflate depression severity given overlapping symptoms. We sought to disentangle fatigue from depression in PICS. Methods: We conducted a cross-sectional analysis of the RAFT COVID study, a national multicenter longitudinal cohort of severe prolonged COVID-19 survivors. We included participants who completed validated surveys at 1-year from hospitalization for depression (PHQ-9) and fatigue (FACIT-Fatigue). We described correlation of FACIT-fatigue with the PHQ9, and separately with PHQ-2 and PHQ-7, which both omit the two items we hypothesized are influenced by fatigue: tiredness and sleeping. Using a MIMIC model, we performed differential item functioning to evaluate the impact of fatigue on depression directly through these two questions and indirectly with the latent depression construct. We then compared PHQ-7 to PHQ-9 scores by fatigue status. Results: Among 82 participants, 61.0% reported fatigue (reverse-scored FACIT-Fatigue[&ge;]9), and 15.9% moderately severe depression (PHQ-9[&ge;]10). FACIT-fatigue was strongly correlated with PHQ-9 (r=.87, p<.001), but less so for PHQ-2 (r=.76, p<.001) and PHQ-7 (r=.82, p<.001). The MIMIC model identified significant direct effects on tiredness ({lambda}=.89, p<.001) and sleep ({lambda}=.52, p<.001). Among fatigued participants, the rescaled PHQ-7 was lower than the PHQ-9 (median of 4.5, IQR 1.50-9.75, vs 7, IQR 4-9.75). Conclusions: Fatigue significantly inflated depression symptoms in severe COVID-19 survivors through tiredness and sleeping PHQ-9 items. PHQ-2 may better screen for true depressive symptoms in PICS, minimizing the risk of misdiagnosis and overtreatment.

Background and AimsAvoidance of symptom-related situations is common in chronic gastrointestinal (GI) conditions, contributing to greater symptom severity, psychological distress, and reduced quality of life. However, no validated measure exists to comprehensively assess GI-specific avoidance. We developed and validated the GI-specific Avoidance Scale (GIAS), a self-report instrument measuring behavioral and cognitive avoidance specific to GI symptoms. MethodsFollowing literature review and multidisciplinary input, an initial pool of 58 items was generated and refined through expert and patient ratings, yielding 37 items. A sample of 102 adults (mean age 40.8 years) with medically diagnosed GI conditions completed the GIAS and validated measures of avoidance, psychological flexibility, illness shame, GI symptoms, distress, and quality of life. Exploratory factor analysis was used to determine factor structure. Internal consistency, convergent validity, incremental validity, and mediation analyses were conducted. ResultsFactor analysis supported a 20-item, three-factor solution: General Avoidance, Food Avoidance, and Intimacy/Body Exposure Avoidance. Internal consistency was excellent for the total scale ( = .94) and good-to-excellent for subscales ( = .82-.94). GIAS scores correlated positively with illness shame, GI symptoms, and distress, and negatively with psychological flexibility, self-compassion, and quality of life. GIAS showed incremental validity over a general illness avoidance measure (IBAS) in predicting GI symptoms and anxiety. Moreover, mediation models suggested that GI-specific avoidance partially mediates bidirectional associations between GI symptoms and psychological distress. ConclusionsThe GIAS is a novel, psychometrically robust, and multidimensional self-report questionnaire of GI-specific avoidance. It holds potential for clinical assessment, treatment planning, and evaluation of intervention mechanisms in GI populations.

BackgroundFood-related gastrointestinal (GI) symptoms are highly prevalent in patients with IBS. Although dietary components may trigger symptoms through luminal mechanisms, cognitive expectations may also shape symptom perception within the gut-brain axis. No validated instrument currently exists to measure food-related symptom expectations. Hence, we developed and validated the Food Expectation Questionnaire (FEX-Q). MethodsThe FEX-Q was developed using a stepwise process including focus group interviews and face-to-face validation to ensure content validity. The finalized digital questionnaire presents 44 food images with six items rated on a visual analogue scale (VAS; 0-100), including the core item assessing food-related symptom expectation ("How severe GI symptoms do you expect after eating this food?"). Additional domains assess taste preference, willingness to eat, perceived healthiness, and perceived fat and carbohydrate content. The finalized FEX-Q was administered in a nationwide online validation survey of adults with IBS and non-IBS controls in Sweden. Participants also completed validated questionnaires including GI symptom severity (combined GSRS), psychological distress (HADS), food-related quality of life (FR-QOL), and a screening tool for food avoidance (NIAS). ResultsTwenty adults with IBS and non-IBS controls participated in the face-to-face validation, resulting in a final version of the FEX-Q comprising 44 food images, which were properly identified and provided a range of macronutrient distributions and trigger foods. In the nationwide online study including 134 patients with IBS and 126 non-IBS controls, the FEX-Q demonstrated strong known-groups validity (mean symptom expectation 18.4 in controls vs 50.1 in IBS), strong construct validity (perceived vs actual fat content r=0.78, p<0.001 and carbohydrate content r=0.59, p<0.001), significant convergent validity with GI symptom severity and food-related quality of life, and high internal consistency (split-half reliability Spearman-Brown corrected r=0.88). ConclusionThe FEX-Q can capture individual food-related symptom expectations to distinct food images. This reliable measurement can be useful to reveal the mechanism of food-related symptom expectations and provide clinically relevant insights for personalized dietary management

BackgroundFunctional motor disorder (FMD) is a common and disabling condition with incompletely understood pathophysiology. Eye-tracking offers a method to objectively examine cognitive and motor control processes and their underlying neural pathways. We aimed to quantify saccade, blink and pupil responses in FMD and healthy controls performing an interleaved pro-/anti-saccade task, and to investigate the relationships between oculomotor measures and motor and non-motor symptom severity. MethodsWe conducted video-based eye-tracking in 104 patients with clinically definite FMD and 115 age- and sex-matched healthy controls performing the saccade task. Patients completed questionnaires on depressive, pain-related, dissociative, non-motor somatic symptoms. Clinician-rated motor severity and centrally acting medication was recorded in FMD patients. ResultsCompared to controls, FMD patients showed increased anti-saccade error rates (p < 0.001), anticipatory saccades (p [&le;] 0.003), altered blink distribution (p < 0.001), and reduced pupil dilation velocity (p < 0.001). However, reduced pupil dilation velocity was not significant in subsample of unmedicated patients. Higher anti-saccade error rates were significantly associated with depressive symptoms, pain severity, dissociative symptoms, non-motor somatic symptom burden, and motor severity (all p < 0.05). ConclusionsWe hypothesize that the altered saccade and blink responses result from altered processing in the frontal cortex and basal ganglia which provide critical input to brainstem oculomotor control areas in FMD. These results support neurobiological models proposing altered predictive and attentional processing underlying FMD. Association between oculomotor measures and symptom severity suggests that specific cognitive abnormalities may play a role in the pathophysiology of these symptoms in FMD. WHAT IS ALREADY KNOWN ON THIS TOPICFMD is increasingly interpreted through predictive coding models suggesting abnormalities in predictions about motor and sensory states driven by abnormally focused attention. Yet the underlying neurobiology remains poorly defined. Empirical studies directly probing basic predictive processes in FMD are scarce, and implicit cognitive-motor interactions, particularly those involving motor learning and adaptation, have been insufficiently explored. WHAT THIS STUDY ADDSOnly two previous studies have used eye-tracking in FMD, focusing mainly on diagnostic saccadic markers. Using time-series analyses of saccadic, blink, and pupillary data, we show abnormalities in inhibitory control, predictive processing, and implicit learning. Due to strong homology between human and primate neurophysiology and neuroimaging findings in oculomotor control, the findings can be linked to dysfunction within cortico-basal ganglia circuits. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYOculomotor abnormalities correlated with motor and non-motor symptom severity, indicating mechanistic relevance. The findings provide empirical support for predictive coding accounts and point to involvement of subcortical structures including projections from the frontal cortex to the basal ganglia. This highlights the value of studying cortico-basal ganglia circuits with implications for treatment and of developing oculomotor measures as potential biomarkers in FMD.

Despite the global prevalence of postpartum depression (PPD), current referral uptake rates are far from satisfactory. While some qualitative studies have investigated factors affecting PPD referrals, a gap in quantitative analysis remains. Addressing this, our study utilized a discrete choice experiment (DCE) to understand the procedural elements influencing PPD referral uptake among diagnosed women. The DCE was conducted via home visits by healthcare providers and a comprehensive mobile app questionnaire. We constructed seven distinct referral attributes to explore participants' preferences, analyzed using mixed logit models and latent class analysis. This analysis identified key determinants and revealed the heterogeneities in referral preferences. A total of 698 individuals completed the DCE questionnaire. All assessed attributes, except for Accompaniment (going to clinic with a family member), were important determinants of preference. Participants generally preferred referrals to psychiatric clinics, face-to-face consultations, lower costs, and shorter waiting times. Significantly, participants' personal and socio-demographic characteristics also played a critical role in their referral preferences. Latent class analysis categorized participants into four distinct groups based on their preferences, with treatment cost and waiting times being the most decisive factors. In conclusion, the preference for PPD referrals is predominantly driven by convenience and access to specialist care. To enhance referral uptake, developing flexible and personalized referral programs that cater to these preferences is crucial.

BackgroundChildhood overweight is a major health concern with long-term consequences. Dutch guidelines recommend that general practitioners (GPs) screen for overweight in children regardless of visit reason, yet GPs infrequently initiate weight-related conversations. ObjectivesTo explore what determines GPs initiation of conversations about childhood overweight, identify the determinants with the highest potential for change, and examine how, in particular, emotional responses and equanimity, relate to GPs intention to initiate conversations. MethodsA cross-sectional survey was conducted among Dutch GPs (in training) between March-May 2025. Behavioural determinants, based on the Theoretical Domains Framework, emotional responses, equanimity, and anticipated behaviour and implementation success were assessed. For all determinants, room for improvement (deviation from maximum), relevance (correlation with anticipated behaviour), and the potential for change (combining these two) were calculated using R. Open-ended responses were analysed using content analysis. Results57 GPs completed the survey. Most reported adequate skills (66%), knowledge (61%), and motivation (74%); yet only 25% reported high implementation success. Their behaviour is constrained by a lack of habituation, negative outcome expectancies, failing to remember to act, and a lack of social and organizational support. Emotional responses were evident, with 10-15% of respondents reporting high arousal or clearly positive or negative valence. Valence, but not arousal or equanimity, was positively associated with anticipated intention (r = 0.45, p < 0.001). ConclusionSupporting routine weight-related conversations requires strategies to strengthen habit formation, reshape outcome expectancies, support memory, address social and organizational factors, and further explore GPs emotion regulation. Key messagesO_LIAlthough highly motivated, general practitioners infrequently initiate conversations about childhood overweight due to existing practical barriers and barriers related to internal processes. C_LIO_LIHabit formation showed the greatest potential for change, emphasizing the importance of automaticity in initiating conversations. C_LIO_LIRegulation of emotions and outcome expectancies, may support GPs in consistently initiating sensitive weight-related conversations. C_LI

ObjectivesFunctional neurological symptoms which do not meet clinical definitions of functional neurological disorder (FND) are common in clinical practice. Understanding the distinction between these benign functional symptoms and FND is crucial in defining FND as an entity for study, and as a clinical syndrome. We aimed to measure the frequency of functional symptoms in people who do not have FND. MethodsA survey was administered to 95 clinicians who attended an international conference on FND. Participants were asked to report the occurrence and characteristics of experiences with features of functional sensory or motor symptoms, or dissociation. ResultsOf the 95 people who responded to the survey, 57.4% reported having experienced any functional symptoms, and 47.9% reported having experienced functional motor or sensory symptoms. The symptoms reported were generally short-lived and caused only mild distress and disruption. Most respondents who reported having experienced a functional symptom reported having had multiple events through their lives. InterpretationThe results suggest that the lifetime occurrence of functional neurological symptoms is at least two orders of magnitude higher than the prevalence of FND. The high prevalence of functional symptoms in people who have never had FND challenges the common assumption that the occurrence of functional neurological symptoms is synonymous with FND. We propose that FND is better conceived of as a failure of the mechanisms by which functional neurological symptoms resolve, rather than the occurrence of functional symptoms per se. This reconceptualization implies new research directions for the underlying aetiology of FND.

Oxytocin is a hypothalamic hormone and neuromodulator that has been linked to a variety of different functions, including parturition, social behavior, and cognitive processing. More recently, oxytocin has also been associated with metabolism and energy balance. However, evidence to date in this field has been inconsistent, especially in human research. To address this, we performed a preregistered systematic review and meta-analysis, which synthesized existing literature on the effect of exogenous oxytocin administration compared to a placebo on caloric intake and appetite in humans, using a living meta-analysis approach. Results indicated a significant, reductive effect of oxytocin administration on appetite in participants belonging to certain patient groups (e.g., obesity or type II diabetes; Hedges' g = -0.21). A separate moderator analysis evaluating oxytocin's effect on caloric intake revealed a conditional effect depending on the patient group, with the obesity group showing a significant effect. We did not find any statistically significant effects in healthy participants. However, further analyses revealed that these effects were also not equivalent, indicating that the data are currently too insensitive to draw clear conclusions. Taken together, the results provide some evidence for the role of oxytocin in regulating appetite in an anorexigenic, possibly homeostatic fashion. Future updates in this living meta-analysis may lead to more definitive conclusions.

ObjectiveTo develop and psychometrically evaluate an assessment of symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) MethodsAn initial symptom list was devised from the relevant literature with the patient and clinician advisory groups. An online survey with 85 symptom items in eight domains was completed by people with ME/CFS. Each item had two response structures (assessing symptom frequency and severity on five-point scales). Rasch analysis assessed each domain for unidimensionality, targeting, internal reliability, item fit and local dependency. ResultsSurvey data (n=721) indicated various item anomalies and inter-item dependencies, leading to item re-formatting or removal. The frequency and severity-based responses broadly replicated each other, and a four-point response format appeared more appropriate than a five-point response format. Following Rasch-based scale amendments, a revised version with a single four-point response format was re-administered to test the modifications. Validation data (n=354) showed the modified scale had an improved response structure and functionality across all domains, satisfying Rasch model assumptions. Additionally, domain-level super-items allowed for a summated total score along with sub-scales summarising neurological and autonomic symptoms, again satisfying Rasch model assumptions. ConclusionsThe Index of ME Symptoms (TIMES) and its associated sub-scales and domain scales are stable, valid assessments of symptoms in ME/CFS.

BackgroundPatients with chronic immune-mediated disorders (IMIDs), including inflammatory bowel disease (IBD), are at increased risk of cardiovascular disease. While advanced therapies show cardioprotective effects in other IMIDs, their impact on major adverse cardiovascular events (MACE) in IBD remains unclear. We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating MACE risk with advanced therapies in IBD. MethodsSystematic search of PubMed, Embase and Cochrane Central identified 43 high-quality studies (36 RCTs,7 observational studies) published between 2002 and 2024. Primary analyses estimated odds ratios (OR) for MACE comparing advanced therapy to placebo, with secondary analyses stratified studies by drug class and length of follow-up. ResultsPlacebo-controlled RCTs showed a nonsignificant trend toward reduced MACE risk (OR: 0.60; 95% CI: 0.24-1.51), with similar findings after continuity correction for zero-event studies (OR: 0.87; 95% CI: 0.45-1.68). Class-specific trends suggested lower MACE risk with IL-12/IL-23 inhibitors (OR: 0.35; 95% CI: 0.05-2.21), JAK inhibitors (OR: 0.57; 95% CI: 0.16-2.06), and a potential increase with anti-TNF agents (OR: 3.04; 95% CI: 0.31-29.47), though none reached statistical significance. Long-term follow-up studies showed consistent findings. Observational studies suggested lower MACE risk for anti-TNF therapies (OR: 0.29; 95% CI: 0.21-0.40), but not for IL-12/IL-23 (OR: 4.41; 95% CI: 0.49-39.28) or JAK inhibitors (OR: 1.57; 95% CI: 0.86-2.84). ConclusionAdvanced therapies did not demonstrate a clear increase or decrease in cardiovascular risk in IBD. The discrepancies between RCTs and observational studies underscore the urgent need for rigorous-designed observational research with long-term follow-up to evaluate the real-world impact of advanced therapies on MACE risk. SummaryThis study evaluated cardiovascular safety of advanced therapies in inflammatory bowel disease. Findings showed no clear signal of decreased major cardiovascular risk compared with conventional treatment, highlighting the need for continued monitoring through long-term and real-world evidence. Key MessagesO_LIWhat is already known? Patients with IBD are at increased risk of cardiovascular events, and the impact of advanced therapies on this risk remains uncertain. C_LIO_LIWhat is new here? This meta-analysis integrates data from randomized and observational studies and found no significant association between advanced therapies and MACE. C_LIO_LIHow can this study help patient care? Findings show no clear signal of decreased cardiovascular risk with advanced IBD therapies, though continued evaluation is warranted. C_LI

BackgroundChronic autoimmune diseases such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Multifocal Motor Neuropathy (MMN), and Thyroid Eye Disease (TED) impose a considerable burden on affected individuals. Patient-reported outcome measures (PROMs)--both disease-specific and generic--are widely used to assess functioning, quality of life, and treatment effects in these populations. However, most PROMs currently lack reference values derived from the general population, limiting the interpretability of patient scores. ObjectiveThe GENESIS (GENEral population normS--An International Survey) study aims to establish general population norms for a range of PROMs used in CIDP, MMN, and TED across six countries: Germany, Italy, Japan, Spain, the United Kingdom, and the United States. These norms will improve patient score interpretation and help quantify unmet needs in patients with these rare autoimmune diseases. MethodsGENESIS is an observational, cross-sectional, online survey of the adult general population (N=21,000). Participants will be recruited to be representative by age, gender, region, and education. The survey includes validated instruments such as the EQ-5D-5L, I-RODS, MMN-RODS, CAP-PRI, GO-QoL, BPI-SF, RT-FSS, FACIT-Fatigue, HADS, and WPAI, along with items on demographics, caregiver need, and healthcare utilization. To reduce respondent burden, participants will be randomized into two groups, each completing a subset of the full questionnaire. A subset of respondents (n=2,333) will be re-surveyed after two months to support psychometric validation. Data will be analyzed descriptively to generate normative values for each PROM by country and in aggregate. Results and DisseminationData collection is scheduled to begin in August 2025, with results expected by Q4 2025. Findings will be disseminated via peer-reviewed publications and conference presentations. ConclusionGENESIS will provide foundational normative data across six countries for PROMs commonly used in rare autoimmune diseases. These data will support more meaningful interpretation of PROM scores in both clinical practice and research settings.

Introduction/Aim: Type 2 diabetes (T2D) is a growing global health burden, with lifestyle behaviors playing a key role in its management. Physical activity (PA), sedentary behavior (SB), and sleep are increasingly conceptualized as interdependent components of 24-hour movement behaviors. While behavior change techniques (BCTs) are commonly used to target individual behaviors, their effectiveness across multiple behaviors in adults with T2D remains unclear. This systematic review and meta-analysis aimed to evaluate the effectiveness of behavior change interventions incorporating BCTs on PA, SB, and sleep outcomes, and to identify effective BCT clusters. Methods: A systematic search of PubMed, Web of Science, and Embase was conducted from inception to December 18, 2023. Randomized and non-randomized controlled trials including adults with T2D were eligible if they evaluated behavior change or lifestyle interventions targeting PA, SB, and/or sleep and included at least one BCT. Data extraction, BCT coding (using the BCT Taxonomy), and risk of bias assessment (Cochrane RoB 2) were performed independently by multiple reviewers. Meta-analyses using random-effects models were conducted for relevant outcomes. Subgroup analyses examined the effects of three common BCT clusters: goals and planning, feedback and monitoring, and social support. Results: Sixty-six studies (n = 18,725 participants) were included. Interventions significantly improved several PA outcomes, including steps/day (+1991 steps/day; p<0.001), total PA (SMD=0.36; p=0.02), moderate-to-vigorous PA (SMD=0.55; p<0.001), and light-intensity PA (SMD=0.62; p=0.01). Sedentary time decreased significantly (SMD=-0.32; p=0.008). Sleep quality improved (MD=-1.39; p=0.02), whereas sleep duration showed no significant change. Subgroup analyses demonstrated that BCT clusters involving goals and planning, feedback and monitoring, and social support were consistently associated with improvements in PA and SB, with comparable effect sizes to overall analyses. Effects on sleep outcomes were limited due to the small number of studies. Conclusion: Behavior change interventions incorporating BCTs effectively increase PA, reduce SB, and improve sleep quality in adults with T2D. BCTs such as goal setting, self-monitoring, feedback, and social support appear particularly beneficial. However, sleep - especially duration - remains underexplored. Future interventions should adopt a 24-hour movement behavior perspective and more explicitly integrate and report BCTs to optimize long-term diabetes management.

Background Chronic pain and depression are leading causes of disability and frequently co-occur. Depression presents with diverse symptoms, but despite this variability, the prevalence of individual depressive symptoms in chronic pain and the genetic and causal associations linking these traits remain poorly characterised. Methods Using data from 142,688 age- and sex-matched UK Biobank participants, we compared depressive symptom severity levels and item-level Patient Health Questionnaire-9 (PHQ-9) prevalences, spanning affective, cognitive and somatic domains, between participants with and without chronic pain. Using genome-wide association study (GWAS) summary statistics of multisite chronic pain (MCP), major depressive disorder (MDD), and individual symptoms of depression, genetic correlations and bidirectional causal effects between MCP and depressive phenotypes (MDD and individual symptoms) were estimated via linkage disequilibrium score regression (LDSC) and two-sample Mendelian randomisation (MR), respectively. Results Depression (at every severity level) was more common in the chronic pain group compared to controls, with the largest between-group difference for severe symptoms (7.50-fold increase). All individual depressive symptoms were at least 2.79 times as prevalent in chronic pain. Additionally, chronic pain had a significant and positive genetic correlation with MDD (rg = 0.59) and all depressive symptoms (rg = [0.24, 0.55]). MR supported a bidirectional causal association between MCP and MDD (MCP[-&gt;]MDD: OR = 1.85, pFDR < 0.001, MDD[-&gt;]MCP: {beta} = 0.17, pFDR < 0.001). At the symptom level, MR indicated bidirectional effects between MCP and anhedonia (MCP[-&gt;]anhedonia: OR = 1.60, pFDR < 0.001, anhedonia[-&gt;]MCP: {beta} = 0.08, pFDR = 0.005), and unidirectional effects of MCP on appetite/weight gain (OR = 1.90, pFDR = 0.022) and appetite/weight loss (OR = 1.63, pFDR = 0.005), concentration problems (OR = 1.63, pFDR = 0.044), and suicidal thoughts (OR = 1.46, pFDR = 0.021). Additionally, genetic liability to concentration problems was associated with a lower risk of MCP ({beta} = -0.04, pFDR = 0.022). Conclusion Chronic pain is associated with a marked depressive burden spanning all symptom domains. Shared genetic architecture and symptom-specific causal pathways, particularly involving anhedonia, highlight potential targets for improved treatment of comorbid chronic pain and depression.

BackgroundPeople with multiple sclerosis (pwMS) often experience impaired quality of life (QoL) despite receiving standard care. Digital therapeutics (DTx) may offer support, but prior trials yielded mixed results, possibly due to active controls and high baseline QoL. We therefore evaluated a DTx (levidex) as an adjunct to treatment as usual (TAU) in pwMS with impaired QoL. MethodsIn this pragmatic, online randomised controlled trial (LAMONT; NCT06090305), n = 470 pwMS with a score [&ge;]2 on the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) were randomised to levidex + TAU or TAU alone. The primary endpoint was HAQUAMS total score at 6 months, analysed by intention-to-treat ANCOVA. ResultsCompared with TAU, levidex + TAU improved MS-specific QoL at 6 months (baseline-adjusted mean difference -0.10; 95% CI -0.18 to -0.03; p = 0.008; Cohens d = 0.26). Clinically relevant HAQUAMS improvement ([&ge;]0.22) occurred more often with levidex (39.5% vs 27.8%; number needed to treat = 9). Benefits also emerged for depressive symptoms and social/work functioning but not for anxiety. No serious adverse events occurred and user satisfaction was high. ConclusionsIn pwMS with impaired QoL, adding the scalable DTx levidex to TAU yields meaningful improvements in QoL and functioning.

IntroductionLow dietary diversity has been identified as a predictor of depression outcomes in high-income countries, while evidence is scarce from low-income settings where poor nutrition and depression often co-occur. In this study, we estimate the relationship between dietary diversity and depression among adults in rural western Kenya. MethodWe conducted a cross-sectional analysis of 311 participants enrolled in the Bridging Income Generation through Group Integrated Care program. We assessed depressive symptoms using the 20-item Centre for Epidemiologic Studies for Depression Scale (CES-D), and measured dietary diversity as the number of five food groups consumed in previous 24-hours using a validated dietary diversity scale. We used linear regression to estimate the association between high dietary diversity (consumption of all the five food groups) and continuous depression scores, adjusting for key covariates. We tested for effect measure modification by wealth status. We conducted a secondary analysis using quantile regression to explore variation across depression scores distributions. ResultsHigher dietary diversity was associated with fewer depressive symptoms [adjusted {beta} (95% CI): -3.49 (-6.62, -0.38)]. The association was stronger among individuals with low wealth backgrounds [adjusted {beta} (95% CI): -6.00 (-10.46, -1.42)] relative to those with high wealth backgrounds [adjusted {beta} (95% CI): -0.53 (-4.76, 3.68); Wald p-value for interaction term =0.0003]. The effect sizes for the association were larger at higher quantiles, notably at 75th [adjusted {beta} (95% CI): -4.00 (-10.13, 2.13)] and 90th [adjusted {beta} (95% CI): -1.59 (-7.43, 4.25)] compared to those at lower quantiles for 10th [adjusted {beta} (95% CI): -0.59 (-2.46, 1.28) and 25th [adjusted {beta} (95% CI): -0.82 (-4.14, 2.50), though wide confidence intervals limited the precision of effect estimates. ConclusionIn rural western Kenya, higher dietary diversity was associated with lower depression symptoms, particularly among participants from lower wealth backgrounds, and particularly among those with scores consistent with more severe depression symptoms. These findings suggest that improving dietary diversity may offer mental health benefit to the most socioeconomically disadvantaged individuals and could be a promising strategy to reduce depression in resource poor settings. Future work could leverage longitudinal and experimental studies for improved inference and should investigate mechanisms through which dietary diversity may influence depression.

ObjectiveComorbidity between urinary incontinence (UI) and affective disorders, including anxiety and depression, is well established in cross-sectional studies and prospective bidirectional associations have also been reported. It is, however, unclear whether these associations are causal. We applied two-sample Mendelian randomization (MR) analysis to examine if there are causal bidirectional relationships between UI and anxiety, depression, and neuroticism in women. Materials and methodsWe used summary level data from independent genome-wide association studies (GWAS) to estimate the bidirectional causal effects of UI and its subtypes (stress urinary incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI), n=10,931) on anxiety (n=83,566), depression (n=1,035,760), broad depression phenotype (n=500,199) and neuroticism (n=329,821). ResultsWe found little evidence of causal effects in either direction, except for weak evidence suggesting that UUI may reduce the risk of depression (causal odds ratio (OR) for depression: 0.99, 95% confidence interval (95%CI) 0.98-1.00; OR for broad depression 0.98, 95%CI 0.96-1.00). However, the direction of effect estimates did not consistently align across sensitivity analysis methods and the magnitude of this effect could be considered negligible. ConclusionOur study provided little evidence for causal bidirectional relationships between UI and anxiety, depression and neuroticism. This study highlights the need for further GWAS of UI (including different subtypes) with larger sample sizes. HighlightsO_LIThere was little evidence for causal bidirectional relationships between urinary incontinence (UI) and anxiety, depression, and neuroticism. C_LIO_LIStudy limitations, including low statistical power, UI phenotype definition, and genetic instrument strength, need to be considered when interpreting the findings. C_LIO_LILarger and more comprehensive GWAS of UI (including subtypes) are needed before ruling out causal relationships between UI and mental health. C_LI

ObjectiveTo evaluate the criterion-related and discriminant validity, test-retest reliability and minimal detectable difference of The Index of ME Symptoms (TIMES) in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) MethodsPeople with ME/CFS in the UK completed the TIMES online (n=1055). Rasch-transformed interval data and parametric statistics were used: Pearson correlations (with the ME severity scale); analysis of variance; intra-class correlations (ICC) and standard error of measurement of ICC measured criterion-related and discriminant validity, test-retest reliability and minimal detectable difference respectively. ResultsHighly significant (P<0.001) moderate (r=0.400-0.528) correlations were seen between the TIMES scales and severity of ME/CFS except the gastro-intestinal and immune systems scales (r= 0.315 and 0.302 P<0.001 respectively). Discriminant validity was demonstrated with significant differences in TIMES scores between all five levels of ME severity, except between levels 4 and 5 in some cases, which were underpowered due to the small group numbers. Test-retest reliability was excellent (ICC>0.7, p<0.001) except the cranial nerves and immune system scales which were good (ICC = 0.681 and 0.669, p<0.001) and minimal detectable difference was excellent (3.95-17.45%). ConclusionsThe Index of ME Symptoms (TIMES) scales are valid, reliable, sensitive assessments of symptoms in ME/CFS. They are freely available for use.

BackgroundHealth-related quality of life is a key secondary endpoint in stroke trials. Differential item functioning (DIF) occurs when individuals with the same underlying HRQOL interpret and respond differently to questionnaire items due to group characteristics, potentially biasing treatment comparisons. This study evaluates DIF in the patient-reported five-level EuroQOL (EQ-5D-5L) among patients with acute ischemic stroke across age, sex, and treatment groups. MethodsData were obtained from the AcT trial, a registry-based randomized comparison of alteplase and tenecteplase. Patients completed the EQ-5D-5L at 90 days post-stroke. DIF was assessed using multigroup graded response models with the Wald-based sweep procedure, which accounts for between-group differences in latent trait distributions. We quantified effect sizes using signed weighted area between curves (sWABC), considering |sWABC| <0.10 as negligible. ResultsAmong 1,264 patients (51.2% tenecteplase; 46.5% female; 30.1% aged [&ge;]80). Omnibus testing revealed significant DIF only for age (X{superscript 2} = 86.9, p < 0.001); neither sex (X{superscript 2} = 31.7, p = 0.063) nor treatment (X{superscript 2} = 22.4, p = 0.379) showed evidence of DIF. At the item level, four items flagged for age-related DIF: self-care, usual activities, pain/discomfort, and anxiety/depression. However, only self-care (sWABC = -0.46) and usual activities (sWABC = - 0.34) showed moderate effects, while pain/discomfort (sWABC = -0.002) and anxiety/depression (sWABC = 0.09) were negligible. Importantly, factor scores from models with and without DIF adjustment correlated (correlation coefficient = 0.98). ConclusionsThe EQ-5D-5L appears to function equivalently across sex and treatment groups in this stroke population. Age-related DIF, though statistically detectable in physical functioning items, had little practical consequence for individual scores, findings that support the instruments use for HRQOL comparisons in stroke trials. RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

ObjectiveTo examine the bidirectional relationships between depression, anxiety, neuroticism, and urinary incontinence in women. DesignA prospective time-to-event and two-sample Mendelian randomisation (MR) study. SettingIndividual participant data from the UK Biobank and summary genome-wide association (GWAS) study data from international consortia. ParticipantsUp to 118 526 UK Biobank women with linked health records and up to 1.6 million participants with GWAS summary data. Main outcome measuresUrinary incontinence (UI) and its subtypes (stress, urge, mixed), urinary urgency (irrespective of leakage), depression, anxiety, and neuroticism. ResultsWe triangulated evidence to demonstrate bidirectional relationships between depression/anxiety and UI. In prospective analyses adjusted for confounders, depression was associated with a higher rate of new onset UI (any UI: Hazard Ratio (HR) 1.67; 95% Confidence Intervals (CI) 1.55 to 1.81) and its subtypes, with the strongest associations observed for mixed UI (HR 1.91; 95%CI 1.59 to 2.31). Similarly, anxiety and higher neuroticism scores were prospectively associated with UI and its subtypes. In the reverse direction, all UI subtypes were associated with a higher rate of new onset depression (e.g. any UI: HR 1.40; 95%CI 1.27 to 1.54) and anxiety (e.g. any UI: HR 1.28; 95%CI 1.17 to 1.39). Two-sample MR provided evidence for a causal effect of genetic liability to depression and neuroticism on UI and its subtypes (e.g. depression on any UI: ORivw; 1.25 95%CI 1.16 to 1.35). Evidence for a causal effect in the reverse direction was weaker, with modest effects of genetic liability to any UI on depression. Little evidence was found for causal effects of anxiety with UI subtypes in either direction. Results were largely robust to sensitivity analyses. ConclusionWe find evidence of bidirectional relationships between depression/anxiety and UI. Evidence that depression, anxiety and neuroticism are predictors of UI onset has implications for treatment. Research is needed to examine if treatments for depression/anxiety could be effective in alleviating UI. KEY MESSAGEO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIUrinary incontinence (UI) co-occurs with depression and anxiety, but the exact nature of the relationship is poorly understood because much of the existing evidence comes from cross-sectional studies. C_LIO_LIAmongst the existing prospective studies, only one used a clinically validated questionnaire to assess UI, few distinguished between UI subtypes (stress, urgency and mixed UI), and some did not adjust for important confounders. C_LIO_LIIt is commonly believed that depression and anxiety are consequences of UI; if they are also causes of UI this has important implications for clinical care. C_LI What the study addsO_LIOur study demonstrates that the relationship between UI and depression/anxiety is bidirectional; We found that depression, anxiety and neuroticism (a personality trait characterised by a disposition to experience depression and anxiety) are predictors of UI onset and that UI is associated with new onset depression and anxiety. C_LIO_LIDepression and anxiety are not routinely assessed in urology clinics, and a continued failure to recognise their contribution to the onset and persistence of UI could be a cause of low success rates of existing treatments for UI. C_LI

BackgroundOur study aimed to investigate the relationship between phenotypic age acceleration (PAA), bowel dysfunction (constipation, diarrhea), and depression severity, and examine whether phenotypic age acceleration can play a mediating role in bowel dysfunction and depression severity. MethodsThe data analysis of our study was conducted from the National Health and Nutrition Examination Survey (2005-2010). Participants with bowel dysfunction were identified on the questionnaire of bowel health. Depression was determined based on the Patient Health Questionnaire-9 (PHQ-9). The calculation of PAA is based on 9 test indicators and actual age; a higher PAA means accelerated aging. In this study, a weighted linear regression model was used to analyze the associations among defecation disorders, PAA, and depression. Restricted Cubic Spline (RCS) curves were applied to explore the potential non-linear relationships between the aforementioned variables. Additionally, a mediation effect model was employed to verify whether PAA could function as a mediating variable in the relationship between defecation disorders and depression. ResultA total of 11,808 participants were included in this study. Linear regression analysis showed that both diarrhea ({beta}=3.73, 95% Confidence Interval (CI): 1.69-8.22, P=1.60x10-3) and depression severity ({beta}=1.08, 95%CI: 1.06-1.09, P=4.61x10-16) were positively correlated with PAA. In addition, both constipation ({beta}=2.76, 95%CI: 1.89-4.04, P=2.28x10-6) and diarrhea ({beta}=4.29, 95%CI: 2.65-6.95, P=2.11x10-7) were positively correlated with depression severity. Further mediation effect analysis revealed that PAA may play a mediating role in the association between diarrhea and depression severity (the proportion of mediation effect in the total population was 7.2285%). When exploring whether PAA exerts a mediating role in the association between constipation and depression severity, it was found that PAA played a mediating role in female participants and participants aged <60 years, except for male participants and those aged [&ge;]60 years (the proportion of mediation effect was 9.8417% in females and 8.4512% in the population aged <60 years, with all relevant P-values <0.005)