Cognitive models of depression implicate impaired executive control, particularly in emotional contexts. However, few studies have directly compared "cold" (non-emotional) and "hot" (emotional) contexts, and the persistence of impairments following remission remains unclear. Diathesis-stress models propose that cognitive vulnerability is latent in remitted depression and emerges under negative mood or stress. This study compared hot and cold executive functioning among currently, remitted, and never depressed individuals, to test whether currently depressed individuals show impairments in hot cognitive control, and whether remitted individuals show impairments following a negative mood induction. Participants were 260 adults who were currently depressed (CD; n = 86), previously depressed (PD; n = 92), or never depressed (ND; n = 82). The pre-registered study protocol, which most participants completed remotely, included computerized inhibition and working memory updating tasks using non-emotional and emotional stimuli and a neuropsychological test battery. PD and ND participants completed tasks at baseline and following a negative mood induction. Contrary to hypotheses, CD participants did not show impaired hot or cold cognitive control, and PD participants did not show impairments following mood induction. CD participants had worse performance on two of eight neuropsychological tasks. Exploratory correlations did not support associations of cold or hot cognitive control with emotion regulation and rumination. These findings suggest that executive functioning deficits may be less consistent and more heterogeneous in depression than previously theorized, even in emotional contexts. Continued research on the relationships between executive control, emotion regulation, and depression vulnerability is needed to refine theoretical models.
Females with infertility perceive stress, but most studies rely on single assessments. We examined the feasibility of repeated ecological momentary assessment (EMA) during IVF and whether stress trajectories across two cycles were associated with reproductive and IVF outcomes. In a prospective cohort at a single academic center, 26 females (18-42 years) undergoing IVF with luteal estradiol priming were recruited; 25 completed follow-up. Perceived stress was assessed via text-message EMA three times daily during a priming month and the subsequent controlled ovarian stimulation (COS) cycle. Primary outcomes were ovulation in the priming cycle and a composite poor COS outcome (cycle cancellation, < 4 oocytes retrieved, no blastocyst, or no euploid blastocyst). Functional principal components analysis characterized stress trajectories, and regression models tested associations with outcomes. Mean age was 36 (SD 3.6); 64% were White and 24% Hispanic. All participants ovulated during priming. Two stress patterns explained 96% of follicular-phase variability. The dominant pattern (early decline then plateau) was not associated with outcomes. A second pattern (peak around cycle day 6 with subsequent rise) was associated with lower peak LH (b - 2.85, 95% CI - 4.60 to - 1.06; adjusted p = 0.004). Ten participants (40%) met the composite poor COS outcome, which was not associated with either stress pattern. Stress levels were similar between priming and COS. EMA is feasible during IVF. In patients reporting mild-to-moderate stress, perceived stress was stable and not associated with key IVF outcomes, though specific trajectories may modestly relate to hypothalamic-pituitary-ovarian-axis function.
Multiple psychiatric disorders are associated with later dementia, but it remains unclear whether these associations reflect a shared liability toward all psychiatric conditions (general psychopathology factor) or diagnosis-specific effects (specific psychopathology factors). In this Swedish register-based cohort study, we investigated these questions while adjusting for familial confounding shared by siblings (N = 2 543 621 individuals, 1 485 880 full-sibling pairs). Exposures were (i) six psychiatric diagnoses recorded by age 35 and (ii) a latent bifactor model fit to these diagnoses that identified one general and three specific (internalizing, externalizing, and psychotic) psychopathology factors. Outcomes were all-cause dementia and Alzheimer's disease recorded after age 50. For observed psychiatric diagnoses, we estimated between-individual (HR) and within-sibling hazard ratios (HRwn) using Cox regression; for latent factors, we estimated between-individual (OR) and within-sibling odds ratios (ORwn) using exploratory structural equation modelling. All psychiatric diagnoses were significantly associated with increased risk of all-cause dementia (HR range 2.03-3.59; HRwn range 1.72-2.94) and Alzheimer's disease (HR range 1.89-3.47; HRwn range 1.77-3.22). These associations were largely attributable to the general psychopathology factor, even after adjusting for familial confounding (ORwn with 95% CI: 1.25 [1.17-1.32] for dementia; 1.24 [1.16-1.32] for Alzheimer's disease). After accounting for the general factor, only the psychotic-specific factor remained associated (ORwn with 95% CI: 1.20 [1.07-1.36] for dementia; 1.20 [1.06-1.37] for Alzheimer's disease). These results suggest that liability toward general psychopathology and, independently, psychotic conditions, by early adulthood might be early markers of increased dementia risk and targets for timely identification and prevention.
Type 2 diabetes mellitus (T2DM) has become a significant health challenge in Africa, with rapidly increasing prevalence. Despite abundant sunlight, vitamin D deficiency (VDD) is prevalent and may influence glucose metabolism and insulin resistance. Genetic factors, including vitamin D receptor (VDR) polymorphisms, may modify these effects. This systematic review and meta-analysis aimed to estimate the prevalence of VDD and evaluate the association of VDR gene variants with T2DM among African populations. We systematically searched PubMed, Cochrane Library, ScienceDirect, Embase, Web of Science, and Google Scholar for observational studies published up to June 11, 2025, reporting VDD prevalence and VDR genetic associations in African individuals with T2DM. Data extraction and quality assessment followed Joanna Briggs Institute (JBI) and PRISMA 2020 guidelines. Pooled prevalence, mean difference and odds ratios (ORs) were calculated using random-effects meta-analysis. Heterogeneity, publication bias, sensitivity analyses, and meta-regression were performed. All statistical analyses were conducted using R version 4.3.1 (2023-06-16 ucrt). Twenty-two eligible studies encompassing 3,447 participants from 11 African countries were included. The pooled prevalence of VDD among individuals with T2DM was 51% (95% CI: 36-65%), with substantial heterogeneity (I2 = 95.7%). Subgroup analyses showed highest prevalence in East Africa (56%). Vitamin D-deficient individuals had significantly higher HbA1c compared to sufficient individuals (mean difference = 0.89%; 95% CI: 0.06-1.72 p = 0.044; I2 = 0%, p = 0.49). The pooled analysis of VDR FokI polymorphisms did not demonstrate a significant association with T2DM risk (OR = 1.51; 95% CI: 0.23-9.73). No evidence of publication bias was detected. Vitamin D deficiency is highly prevalent in African populations with T2DM and is associated with poorer glycemic control. Current evidence is insufficient to conclude on VDR FokI polymorphisms and T2DM risk. These findings underscore the need for interventional trials to determine whether improving vitamin D status enhances glycemic outcomes; routine screening or supplementation recommendations remain premature. CRD420251134616.
In patients with psoriatic arthritis, articular responses vary by joint location with both tumour necrosis factor inhibitors (TNFi). It remains unknown whether this also applies to patients with axial spondyloarthritis (axSpA). We included patients with axSpA from the European spondyloarthritis research collaboration network (EuroSpA RCN) who initiated a TNFi between 2001-2022. Joint tenderness was used as a proxy for peripheral articular involvement. Among patients with at least one tender joint at treatment start (baseline) based on a 26-joint count (28-joint count excluding the shoulders), resolution of joint tenderness during a two-year follow-up was assessed with a mixed-effects model for interval-censored data, including random effects for country and patient. A total of 1113 patients (43.4% male, mean (SD) age 44.7 (11.7) years) with 5886 tender joints (median (IQR) 3 (2,7) tender joint count) from eight European countries initiating treatment with a TNFi (N=1113) were included. The knee and wrist were most commonly affected at baseline. Compared with the wrist, the rate of joint tenderness resolution was similar in the elbow (HR=1.06, 95%CI 0.88 to 1.28), lower in the knee (HR=0.76, 95%CI 0.64 to 0.90), while higher in all finger joints, particularly in the first interphalangeal joint (HR=2.64, 95%CI 2.05 to 3.40) and in digits four and five (metacarpophalangeal joint (MCP)4 HR=2.19, 95%CI 1.77 to 2.71) and MCP5 (HR=3.16, 95%CI 2.50 to 4.00) Conclusion: The peripheral joint response to TNFi in axSpA appears to be location-dependent, indicating that the joint site should be considered when interpreting treatment response.
Youth from minoritized backgrounds face significant inequities in accessing and benefiting from evidence-based mental healthcare. Although decades of research highlight the central role of sociocultural context in shaping mental health needs and treatment outcomes, current evidence-based interventions (EBIs) rarely provide explicit guidance for addressing the intersecting sociocultural experiences of minoritized youth. In this article, we synthesize approaches to culturally responsive care and argue for a shift toward person-centered culturally responsive (PCCR) treatment. PCCR treatment is an individualized, practice-oriented approach that flexibly integrates youth and family cultural identities, contextual stressors, and strengths. Using the development of the Revamping Evidence-based Supports to Promote Effective Culturally Responsive Treatment (RESPECT) toolkit as an illustrative example, we outline a systematic, community-engaged, practice-based process for supporting PCCR treatment within exposure-based CBT. We then identify key gaps in the current evidence base, including limited operationalization of PCCR strategies, insufficient research on their effectiveness and mechanisms, and the lack of implementation strategies to support clinician training, decision-making, and sustainment. Finally, we propose future directions to support a path toward advancing PCCR treatment that prioritizes practice-based community-engaged methods.
Participation in online communities centered around self-harming and suicidal behavior is a complex phenomenon characterized by potentially harmful social dynamics, though it may also involve support. While previous studies have explored peer support within these communities, less is known about how engagement may influence personal recovery and the functions these communities serve. Therefore, this study explored experiences of personal recovery in the context of participating in unmoderated online communities centered around self-harming and suicidal behavior. This qualitative deductive-inductive secondary analysis re-examined interview data originally collected to explore peer support exchanges within online communities centered around self-harm and suicidal behavior, using reflexive thematic analysis informed by the CHIME-D (Connectedness, Hope, Identity, Meaning, Empowerment, and Difficulties) framework to examine personal recovery in this context. The dataset consisted of semi-structured interviews with twelve women and one non-binary participant (aged 21-49 years) from all five Danish regions, all with lived experience of psychiatric disorders and previous psychiatric admissions. Participants described how engagement supported personal recovery through mutual recognition, reciprocity, and shared experience. They also described tensions between their own experiences of these communities as meaningful recovery spaces and professionals' predominantly risk-oriented interpretations, contributing to stigma and concealment. Recovery was experienced as complex and ambivalent, involving not only support but also ongoing attachment, emotional burden, and difficulty disengaging. Participants also described challenges related to moral responsibility towards others, exposure to distressing content, and balancing recovery with ongoing participation. Examining recovery in digital self-harm networks highlights important nuances in understanding the roles and functions these networks may serve. Applying the CHIME-D framework provided a nuanced understanding of how online communities centered around self-harming and suicidal behavior may contribute to personal recovery, advancing our understanding of the functions they serve and what motivates participation. The findings highlight recovery as a non-linear process shaped by both supportive and challenging dimensions of online engagement and underscore the importance of recognizing these communities as meaningful, though double-edged, contexts for recovery.
The Government of Kenya plans to scale-up an adolescent-focused cash 'plus' programme to improve educational attainment and prevent adolescent pregnancy. We aimed to estimate the programme's impacts, economic returns, and cost-effectiveness using model-based economic evaluation. We modelled the delivery of conditional cash transfers 'plus' adolescent clubs, community conversations, parenting support and psychosocial support to poor adolescents in nine selected counties from 2026 to 2029. Two scenarios were compared: a baseline in which intervention variables remained constant at 2025 levels, and an immediate scale-up sustained throughout 2026-2029. Human development impacts were simulated using an integrated modelling framework. Gains in years of schooling were projected with an education transition model, while reductions in adolescent pregnancy, child marriage, and experiences of violence were estimated with a deterministic age-cohort transition model. Economic returns to schooling were calculated with Mincerian earnings functions. Model parameters were derived from rigorous impact evaluations, nationally representative surveys, and Kenya's national social registry. The four-year intervention, costing US$46.1 million, is projected to reach 140,000 adolescents, and compared with the baseline, generate an additional 74,900 (+7%) years of schooling; and avert 1,420 (-8%) adolescent pregnancies, 1,500 (-11%) child marriages, 2,970 (-3%) experiences of sexual violence, and 21,800 (-8%) experiences of emotional/physical violence. Furthermore, the intervention is projected to generate US$318 million in discounted lifetime labour earnings, representing a seven-fold return on investment. The estimated cost was US$567 per additional year of schooling, and US$109 when benefits across multiple outcomes were considered, comparing favourably with other adolescent education interventions. Findings were robust to sensitivity analyses, with a >98% probability that returns exceeded programme costs. These findings suggest that scaling up an adolescent focused cash 'plus' programme could substantially improve adolescent human development, while delivering strong economic returns and good value for money.
Per- and polyfluoroalkyl substances (PFAS) are persistent xenobiotics linked to neurodevelopmental, neurodegenerative, and neurological disorders. PFAS-induced gut microbiota remodelling may disrupt gut-brain signalling, thereby affecting brain functions and behaviour. Integrating microbiome endpoints (diversity, taxonomic shifts, and metabolic configuration) into PFAS research provides a framework to elucidate toxicodynamic mechanisms and to inform the development of targeted, mechanism-based therapeutic strategies.
Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. A randomized controlled trial. A tertiary general hospital. A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n = 65) or routine nursing only (n = 65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6 months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6 months ranged from small for resilience (D = 0.28) and avoidance coping (D = 0.26) to moderate for confrontation coping (D = 0.60) and resignation coping reduction (D = -0.51), and large for attributional style (D = 0.94). Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.
Low-level alcohol consumption at or below current guidelines (≤1 standard drink equivalent/day for females, ≤2 standard drink equivalents/day for males) has been indicated to carry minimal systemic health risks. This study assessed the relationships between alcohol consumption over 1- and 3-years prior to study and over lifetime and measures of manual dexterity and postural stability in healthy adults with low-level alcohol consumption. Healthy, non-smoking adults (n = 83; 21-69 years old) completed measures of dominant and non-dominant hand dexterity, complex motor coordination and motor speed (Lafayette Grooved Peg Board), and static postural stability (Sharpened Romberg Test; eyes open and eyes closed conditions). Alcohol consumption over 1- and 3-years prior to study, and over lifetime, was acquired via the Lifetime Drinking History. The greater multiplicative product of age and total lifetime drinks was related to poorer dexterity, complex motor coordination and motor speed for the dominant hand, and for the summed performance across the dominant and non-dominant hands. Greater lifetime average drinks/month was related to poorer static postural stability, with eyes closed. Males and females showed equivalent performance across dependent measures. Findings indicated higher lifetime alcohol consumption, at a level that has been historically regarded as low risk for adverse functional consequences, was associated with poorer performance on established clinical and research measures of manual dexterity, complex motor coordination and motor speed, and static postural stability. These results may have implications for current alcohol consumption public health guidelines and associated policies.
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The convergence of neurological, psychiatric, neurodevelopmental, and public health approaches to brain health is reshaping global strategies for prevention, care, and policy. However, major gaps remain in the integration and implementation of brain and mental health frameworks across healthcare systems and regions. This paper describes the foundation and early development of the International Alliance on Brain Health (IABH), established in Switzerland in 2025 to promote interdisciplinary collaboration, reciprocal innovation, and implementation-oriented exchange between the global North and global South. Drawing on the Alliances founding meeting in Bern, its contribution as a partner to the World Brain Health Forum organized by the Paris Brain Institute, and its subsequent meeting in Buenos Aires, the paper outlines the Alliance's global positioning and priorities for translating brain health frameworks into practice. Key themes included integrated neurological and mental health approaches, prevention across the life course, digital innovation, brain capital, workforce development, and stronger inclusion of global South perspectives in international policy dialogue. The Alliance also emphasized bidirectional learning and locally adaptable implementation strategies aligned with WHO brain health frameworks. Under the joint patronage of the World Federation of Neurology and the World Psychiatric Association, the IABH represents an emerging platform for cross-continental collaboration in brain health.
Early recognition of cognitive impairment (CI) and timely diagnoses of mild CI (MCI) and Alzheimer's Disease and Related Dementias (ADRD) are key to optimal dementia care. No previous research has examined the extent to which healthcare interventions/services (specific blood tests, specialist referrals, and brain imaging) conducted after annual wellness visits (AWVs) contribute to subsequent MCI/ADRD diagnosis. We assessed the role of post-AWV healthcare services on the association of incident AWVs with the first ADRD or MCI diagnosis in Medicare enrollees. Propensity score matching of AWVs generated an active comparator cohort of Texas fee-for-service Medicare enrollees who received a Primary Care Provider visit, but without AWVs in 2018 (n = 66,443 in each group). Healthcare services (laboratory testing for CI: vitamin B12, thyroid stimulating hormone; specialist referrals: neurology, psychiatry; and brain images: CT, MRI) occurring after AWV and before the first MCI/ADRD diagnosis were examined. Both groups had similar proportions of patients receiving specific blood tests, specialist referrals, and brain images in the 12 months before AWV/index date. Among those with no previous specialist visits, 39.2% in the AWV group and 31.1% in the non-AWV group received laboratory testing in the follow-up period. Similarly, among those with no previous brain images, 12.4% in the AWV group and 13.1% in the non-AWV group received brain images in the follow-up period. AWV receipt was associated with a 28% increase in MCI diagnosis; mediation analyses indicated that 14% of this increase was explained through post-AWV laboratory testing. AWV receipt was not associated with an increase in ADRD diagnosis. Medicare AWV had a large direct effect on MCI diagnosis, but not on dementia diagnosis, suggesting that cognitive assessment and clinical evaluations during AWV directly contributed to the early recognition of MCI.
Tuberous sclerosis complex (TSC) is associated with intellectual disability (ID), autism spectrum disorder (ASD), and TSC-associated neuropsychiatric disorders. Early prospective studies have characterized neurodevelopmental outcomes in infants and toddlers with TSC. Leveraging longitudinal data from the TSC Autism Center of Excellence Research Network and the Rare Diseases Clinical Research Network, we examined longer-term developmental trajectories and ASD diagnostic stability in a cohort of children with TSC. Participants were originally enrolled in TSC Autism Center of Excellence Research Network and followed through 36 months and then subsequently enrolled in Rare Diseases Clinical Research Network for continued follow-up. Longitudinal neurodevelopmental assessments were performed. Analyses focused on participants' most recent assessment to accommodate study overlap and missing data. Outcomes were compared by ASD status, sex, and adaptive functioning. Thirty-two participants with TSC (50% female; mean age 4.5 years) were included. Cognitive and adaptive functioning scores were generally in the delayed range and remained relatively stable over time. At the most recent visit, 48% met criteria for ASD, with ASD diagnosis remaining stable in most participants. Lower adaptive functioning was significantly associated with ASD diagnosis (P = 0.016) and greater social and behavioral impairment. Females demonstrated significantly higher levels of social impairment on the Social Responsiveness Scale, Second Edition compared to males, even after adjusting for ASD diagnosis. Early cognitive and adaptive assessments in children with TSC inform later neurodevelopmental outcomes. While ASD diagnosis is largely stable over time, subtle social impairments may be under-recognized. Routine, longitudinal screening for TSC-associated neuropsychiatric disorders symptoms is essential to support timely identification and intervention in TSC.
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Body image disturbance (BID) is a key symptom of anorexia nervosa (AN) and involves body size overestimation. Although this overestimation might be related to perceptual deficits, little is known about tactile perception in AN. To clarify the role of putative tactile deficits in BID, the present study investigated 36 adolescent female AN patients and 41 matched healthy controls (HC) using a tactile oddball paradigm during parallel EEG and MEG (EMEG) measurement. Tactile perception was behaviorally tested via the Touch Test (tactile perception threshold), a deviant count task, and a tactile stimulus discrimination task. Compared to HC participants, AN patients had similar tactile perception thresholds, but performance in the deviant count task and the tactile stimulus discrimination task was poor. Non-parametric cluster permutation tests on estimated neural source activity of evoked EMEG responses revealed that AN patients and HC did not differ regarding the neural differentiation between deviant and standard stimuli (oddball effect). However, estimated neural activity was globally reduced in the inferior temporal cortex and (by trend) in the posterior parietal cortex. These findings argue against the idea that behavioral discrimination deficits of tactile stimuli in AN are grounded in neural stimulus discrimination deficits. Instead, the overall reduced neural activity in the inferior temporal and posterior parietal cortex might reflect aberrant integration of neural tactile representations into a coherent multisensory body representation.
Exercise-induced muscle-brain communication mediated by extracellular vesicles. Physical exercise stimulates skeletal muscle to release extracellular vesicles (EVs) into the circulation. These vesicles may reach the brain and transfer bioactive cargo such as miRNA, thereby supporting neuronal function and brain homeostasis and potentially protecting against the onset or progression of neurodegenerative diseases.