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The relationship between composite dietary antioxidant index and odds of depression: A systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: Recently, the association between the composite dietary antioxidant index (CDAI) score and depression has received special attention from researchers. However, this possible association has not been comprehensively examined. Thus, the present study aims to comprehensively assess the relationship between CDAI score and depression odds. METHODS: A thorough literature search was performed using Scopus, PubMed, and Web of Science up to November 2025. Observational studies assessing the relationship between CDAI score and depression odds were included. The odds ratios (ORs) and their 95% confidence intervals (CIs) reported in each study were extracted, and a pooled effect size was calculated using a random-effects model with inverse-variance weighting. RESULTS: Four observational studies were included in the current systematic review and meta-analysis. The pooled effect size indicated that a higher CDAI score was associated with lower odds of depression (OR:0.62; 95%CI: 0.51-0.76, I2&#xa0;=&#xa0;48.5%; P-value&#xa0;=&#xa0;0.121). In an exploratory linear dose-response analysis based on two eligible studies, no significant association was observed between a one-unit increase in CDAI score and the odds of depression (OR&#xa0;=&#xa0;0.96; 95% CI: 0.91-1.02; I2&#xa0;=&#xa0;92.2%; P-value<0.001). Given the limited number of studies and substantial heterogeneity, these findings should be interpreted cautiously. CONCLUSIONS: Our findings suggest that higher CDAI scores, reflecting greater adherence to antioxidant-rich dietary patterns, are associated with lower odds of depression.

Humans

A systematic review and meta-analysis of the late positive potential and internalizing psychopathology.

The present study leveraged the Hierarchical Taxonomy of Psychopathology (HiTOP) framework to conduct a systematic meta-analysis to determine the association between the late positive potential (LPP) index of emotional reactivity and internalizing psychopathology. PRISMA guidelines were followed. Articles were identified through PubMed, APA PsycInfo, and Web of Science online platforms in May 2025. Included articles examined associations between the LPP to positive and/or negative stimuli and internalizing psychopathology. Risk of bias and publication bias were assessed. Results were examined for individual disorders, distress and fear subfactors, and the internalizing spectrum using two approaches: standard analyses that examined aggregate effects and hierarchical analyses that examined direct and indirect relationships. We conducted moderator analyses for sample, task design, LPP quantification, and psychopathology measurement. We included 63 studies across 5,360 participants (Mage = 19.65, SD = 11.1; 58.7% female). In standard meta-analyses, depression was associated with a smaller LPP to positive stimuli (r = -.06, 95% confidence interval [CI; -.12, -.003]). Specific phobia was associated with a larger LPP to negative stimuli (r = .21, 95% CI [.02, .37]). Distress was associated with a smaller LPP to both positive (r = -.12) and negative (r = -.11) stimuli when measured via clinical interview, and fear was associated with a larger LPP to negative stimuli (r = .10, 95% CI [.03, .16]). Hierarchical analyses indicated that the depression results were specific to the disorder, whereas the fear disorder-level results were due to the higher order fear subfactor. The LPP demonstrates discriminant relationships with distress and fear disorders and subfactors. Results were largely robust against methodological factors. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Humans

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals

Targeting depression before it starts: An updated systematic review and meta-analysis of preventive interventions in young adults from randomized controlled trials.

INTRODUCTION: Young adulthood is a high-risk period for major depressive disorder (MDD) onset yet is underrepresented in prevention research. This systematic review and meta-analysis examined the effectiveness of psychosocial preventive interventions in adults aged 18-25&#xa0;years, focusing on symptom reduction, medium- and long-term effects, and MDD onset. METHODS: We conducted a PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD42024625481) of randomized controlled trials (RCTs) of psychosocial preventive interventions for depression in young adults (18-25) published up to April 15, 2025. Between-group symptom reduction was quantified using Hedges' g and pooled with random-effects models. Outcomes were analyzed at post-intervention, 6-, and 12-month follow-up. Effects on MDD onset were assessed via risk ratio (RR). Risk of bias was assessed with the RoB-2 tool. RESULTS: We included 65 interventions from 58 RCTs (N&#xa0;=&#xa0;11,333; mean age 20.4; 61.6% female), with 92.8% rated high risk of bias. Interventions at post-test reduced depressive symptoms vs. controls (k&#xa0;=&#xa0;65; g&#xa0;=&#xa0;-0.52; 95%CI:-0.70;-0.33; p&#xa0;<&#xa0;0.01), with significant heterogeneity (I2&#xa0;=&#xa0;93.0%). Indicated, guided, and face-to-face interventions outperformed universal, selective, self-guided, and online interventions. Effects on symptomatology were highly heterogeneous and non-significant at 6- (k&#xa0;=&#xa0;8) and 12-month (k&#xa0;=&#xa0;4) follow-up. Four RCTs were identified evaluating MDD onset risk; pooled effects suggested a reduction in MDD onset (RR&#xa0;=&#xa0;0.77; 95%CI:0.61;0.97; p&#xa0;<&#xa0;0.01) though risk of bias was high and samples were highly selective. INTERPRETATION: Psychosocial preventive interventions modestly reduce depressive symptoms at post-test and may lower onset risk in highly selective populations. However, findings remain limited by high risk of bias, scarce data on the long-term sustainability of effects, and unclear mechanisms.

Adolescent

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's &#x3ba;. Agreement was rated as strong where measures were &#x2265;&#x2009;0.50, moderate where agreement was 0.30-0.49, and weak where <&#x2009;0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

PHACE syndrome: a systematic literature review and illustrative case report of a patient with severe cerebrovascular and neurodevelopmental sequelae.

BACKGROUND: PHACE syndrome is a rare neurocutaneous disorder defined by the association of large segmental infantile hemangiomas of the head and neck with malformations of the posterior fossa, cerebral and cervical arteries, heart, eyes, and ventral midline structures. Although facial hemangiomas are often the presenting feature, the cerebrovascular, neurodevelopmental, and airway manifestations are responsible for the greatest long-term morbidity. METHODS: A systematic literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Web of Science, EMBASE, and PsycINFO. After removal of duplicates and screening of 308 records, five studies meeting the inclusion criteria were retained for qualitative synthesis. We additionally present the case of a now 12-year-old girl with PHACE syndrome characterized by a left V1-distribution facial hemangioma, ocular abnormalities, multiple cerebrovascular venous and arterial malformations, neonatal intraventricular hemorrhage with hydrocephalus, and a subsequently diagnosed dural arteriovenous fistula requiring repeated embolization. RESULTS: The five included studies collectively describe epidemiology and early supportive care needs, long-term health outcomes and quality of life into adulthood, airway hemangioma prevalence and management, and the clinical spectrum of infantile hemangiomas with minimal or arrested growth (IH-MAG) as a cutaneous marker of PHACE syndrome. Across studies, cerebrovascular arteriopathy (72-91%) and facial hemangioma residua (>&#x2009;90%) were the most consistent findings, while progressive arteriopathy, headaches, learning differences, and airway involvement emerged as the principal sources of long-term morbidity. The reported case illustrates an unusually severe cerebrovascular phenotype, including neonatal hemorrhagic hydrocephalus, dural venous sinus thrombosis, and a late dural arteriovenous fistula, culminating in ataxic cerebral palsy and mild intellectual disability. CONCLUSIONS: PHACE syndrome requires a multidisciplinary, lifelong follow-up strategy. The presented case underscores that cerebrovascular complications may evolve over years to decades after the initial diagnosis, reinforcing the need for long-term neuroradiological surveillance even after apparent clinical stability.

Humans

Substance use and co-occurring mental health conditions among adolescents and young adults in North America: a systematic review.

BACKGROUND: Substance use and co-occurring mental health conditions are common among adolescents and young adults and represent an important clinical and public health concern in North America. Trauma exposure, psychiatric symptoms, and social adversity frequently co-occur with substance-related problems in this population. This systematic review aimed to synthesize evidence on prevalence patterns, associated clinical and psychosocial factors, and care-related implications described in the literature on adolescents and young adults with substance use and co-occurring mental health conditions. METHODS: This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024581685). A systematic search was conducted in MEDLINE (Ovid), Embase, PsycINFO, and Google Scholar. Eligible studies examined adolescents and young adults (&#x2264;&#x2009;25 years) in North America. A combination of subject headings, keywords, and synonyms for the concepts "adolescents," "young adults," "substance use disorders," and "co-occurring mental health conditions" was used. Of 1,882 records identified, 29 studies met the inclusion criteria. Given the heterogeneity of the literature, findings were synthesized narratively. RESULTS: The included studies showed heterogeneity in population, setting, denominator, and ascertainment method. Across the literature, depressive, anxiety-related, trauma-related, and externalizing mental health presentations were frequently reported alongside substance-related problems in adolescents and young adults. Trauma exposure, adverse childhood experiences, and broader social adversity were also commonly reported in association with substance-related problems across studies. Care-related implications were more limited and were largely derived as future directions mentioned across studies rather than direct evaluations of youth-specific service models. CONCLUSION: Co-occurring mental health and substance-related problems were frequently reported among adolescents and young adults in high-risk and service-engaged populations in North America. Trauma and social adversity were prominent across the reviewed literature, while direct evidence for evaluated, integrated, youth-specific care models remains limited. These findings support the relevance of developmentally appropriate, integrated, and trauma-informed approaches to care and highlight the need for further research directly evaluating improved service delivery models for this population. CLINICAL TRIAL NUMBER: Not applicable.

Humans

Intravenous Ketamine reduces psychological pain in suicidal inpatients: A secondary analysis of a six-week randomized placebo-controlled trial.

BACKGROUND: Psychological pain has been conceptualized as an unbearable inner experience and a possible precondition for suicidal ideation. No randomized placebo-controlled study has specifically investigated psychological pain as a treatment target in psychiatric populations. We examined ketamine's effect on psychological pain in suicidal psychiatric inpatients. METHODS: This secondary analysis used KETIS, a 6-week randomized, double-blind, placebo-controlled trial. Participants received two 40-minute intravenous infusions of ketamine (0.5&#xa0;mg/kg) or placebo (0.9% saline) 24&#xa0;h apart, alongside usual care and medication. Psychological and physical pain were assessed at baseline, repeatedly during 96&#xa0;h, and at weeks 2, 4, and 6 using the self-rated PPP-VAS. Longitudinal mixed models compared pain trajectories. RESULTS: The trial randomized suicidal inpatients to ketamine (n&#xa0;=&#xa0;73) or placebo (n&#xa0;=&#xa0;83). Psychological pain decreased in both groups but was lower with ketamine during the first 96&#xa0;h. Pointwise scores were lower with ketamine from 40&#xa0;min to 96&#xa0;h, largest at 40&#xa0;min, 2&#xa0;h, 4&#xa0;h, and 24&#xa0;h (all p&#xa0;<&#xa0;0.001), but not at weeks 2, 4, or 6. This early difference remained significant after adjustment for depressive symptoms and hopelessness. The early reduction appeared more pronounced in the bipolar subgroup. No robust baseline predictors of outcome were identified. CONCLUSIONS: Intravenous ketamine was associated with a greater reduction in psychological pain than placebo in suicidal inpatients, with the clearest effects emerging within the first hours after treatment and remaining evident through the first 96&#xa0;h. Ketamine may represent a clinically relevant option as a psychological pain reliever in psychiatric patients.

Humans

Psychotherapy vs antidepressants in heart failure: Impact of adherence.

BACKGROUND: Depression affects nearly half of patients with heart failure (HF), which is associated with increased morbidity and reduced health-related quality of life (HRQoL). This secondary per-protocol analysis of a previously published randomized trial evaluated the behavioral activation (BA) versus antidepressant medication (MEDS) among patients with depression and HF who adhered to study interventions. METHODS: This analysis is based on a pragmatic randomized comparative-effectiveness trial conducted from 2018 to 2022, with a 1-year follow-up. 416 participants diagnosed with HF and a DSM-5 depressive disorder were randomized to BA or MEDS, and the current analysis examined outcomes according to treatment adherence. OUTCOMES: The primary outcome was depressive symptom severity (PHQ-9) at 6&#xa0;months, and the secondary outcomes were physical and mental HRQoL (SF-12v2-PC and SF-12v2-MC, respectively) and HF-specific HRQoL (Kansas City Cardiomyopathy Questionnaire; KCCQ) overall and clinical scores (KCCQ-OS and KCCQ-CS), at 3, 6, and 12&#xa0;months. High adherence was defined as completion of >75-100% of intervention components. Overall adherence rates were similar between BA and MEDS. At 6&#xa0;months, among patients with >75-100% adherence who followed treatment as directed in both arms, BA was associated with higher Mental HRQoL (SF-12v2-MC: 5.22; 95% CI: 0.72 to 9.72; p&#xa0;=&#xa0;0.023) and higher HF-specific HRQoL (KCCQ-OS: 16.08; 95% CI: 7.20 to 24.97; p&#xa0;<&#xa0;0.001); (KCCQ-CS: 16.04; 95%CI: 7.05 to 25.02; p&#xa0;<&#xa0;0.001) compared to MEDS. There were no significant differences in depressive symptoms or physical HRQoL at 6&#xa0;months. INTERPRETATION: Both BA and MEDS were equally effective treatments for depression in HF. However, among highly adherent patients, BA was associated with greater improvements in mental and HF-specific HRQoL than MEDS. FUNDING/SUPPORT: The study was funded by PCORI Award Number: 2017C2-7716.

Humans

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS&#x202f;&#xd7;&#x202f;RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans

Atypical cytokine profiles in people on the autism spectrum: a comprehensive systematic review and meta-analysis including 54 cytokines.

Atypical peripheral blood cytokine concentrations have been shown in autism, but no clear pattern has been observed. This systematic review and meta-analysis summarised current state of findings, expanded the range of cytokines, accounted for study risk of bias, and examined relations between cytokines and autism traits. Literature comparing peripheral blood cytokine in autistic and non-autistic people was systematically searched in Ovid&#xae; Embase, MEDLINE and APA PsycINFO, Web of Science&#x2122; and Scopus, resulting in 98 studies and 54 cytokines (4236 autistic, 3333 non-autistic controls; age 2 to 65 years) in the meta-analysis. Study risk of bias was assessed using adapted Newcastle-Ottawa Scale. Compared to controls, autistic people had elevated levels of IL1-beta (Hedges' g&#x2009;=&#x2009;0.620, 95%CI[0.32, 0.92]), IL4 (g&#x2009;=&#x2009;0.245, 95%CI [0.07, 0.42]), IL6 (g&#x2009;=&#x2009;0.365, 95%CI [0.011, 0.62]), IL8 (g&#x2009;=&#x2009;0.384, 95%CI [0.15, 0.62]), IFN-gamma (g&#x2009;=&#x2009;0.404, 95%CI [0.09, 0.72]), TNF-alpha (g&#x2009;=&#x2009;0.31, 95%CI [0.11, 0.51]), CXCL1/GRO-&#x3b1; (g&#x2009;=&#x2009;0.364, 95%CI [0.058, 0.670]) and MIF (g&#x2009;=&#x2009;0.560, 95%CI [0.14, 0.98]). Over a third of studies were classified as having a high risk of bias; their removal revealed higher IL7 and IL1RA in autism relative to controls. Narrative synthesis produced no strong evidence for an association between cytokine and autism traits among autistic individuals. Altogether, our findings support a predominance of pro-inflammatory cytokines, while also indicating potential modulatory contributions from inhibitory cytokines, which reflect group-level differences between autistic and non-autistic individuals, but not variations of autism traits within the autistic population. However, higher-quality studies with low risk of bias are needed before firm conclusions can be drawn.

Humans

A pragmatic randomized controlled trial of self-directed online writing interventions for posttraumatic stress symptoms in a real-world digital setting.

Background: Public health and other large-scale crises, such as the COVID-19 pandemic, have intensified the global mental health burden, creating unprecedented demand for accessible interventions for posttraumatic stress symptoms (PTSS).Objective: We evaluated the feasibility and effectiveness of two self-directed online writing interventions embedded within China's WeChat ecosystem during the COVID-19 pandemic through a pragmatic randomised controlled trial.Methods: Between December 2021 and August 2022, 1,526 adults were screened for PTSS via a Tencent Medinfo Mini-Program. Eligible participants (n&#x2009;=&#x2009;211) were randomised to Guided Narrative Technique-Writing (GNT-W, n&#x2009;=&#x2009;100) or Expressive Writing (EW, n&#x2009;=&#x2009;111). Both interventions comprised three self-directed daily writing sessions delivered entirely online without human support. Primary outcome was PTSD symptom severity (PTSD Checklist-Short), assessed at baseline, post-intervention, 2-week, and 1-month follow-ups.Results: While initial engagement followed typical digital health patterns (64.5% overall attrition), participants who initiated treatment showed strong adherence (77% completion). Both interventions were associated with significant within-group reductions in PTSS severity (GNT-W: b&#x2009;=&#x2009;-0.43, p&#x2009;=&#x2009;.023, d&#x2009;=&#x2009;-0.43; EW: b&#x2009;=&#x2009;-0.60, p&#x2009;=&#x2009;.001, d&#x2009;=&#x2009;-0.58), with no significant between-group difference (group &#xd7; time: b&#x2009;=&#x2009;0.18, p&#x2009;=&#x2009;.48). GNT-W did not confer additional benefit over EW protocol on PTSS severity.Conclusions: Both self-directed writing interventions were associated with within-group reductions in PTSS; without an inactive control condition, however, these changes cannot be firmly attributed to the interventions. GNT-W showed no advantage over the simpler EW protocol. These findings offer preliminary support for embedding scalable, low-barrier writing interventions in widely used digital platforms.Chinese Clinical Trial Registry: ChiCTR2000034836.

Humans

A Systematic Review of Help-Seeking Barriers for Racial-Ethnic Minority Caregivers Accessing Autism Diagnostic and Intervention Services.

Caregivers play an essential role in early help-seeking and intervention for children with Autism Spectrum Disorder (ASD). Caregivers, therefore, provide a crucial role in helping to address the racial and ethnic disparity identified in accessing ASD intervention and diagnostic services (Bejarano-Mart&#xed;n et al., Journal of Autism and Developmental Disorders 50(9), 3380-3394, 2020). Unfortunately, racial-ethnic minority caregivers of children with autism (CCA) are less likely to contact a physician or healthcare professionals about their concerns and more likely to delay their contact to have their child evaluated (Zeleke et al., Journal of Autism and Developmental Disorders 49(10), 4320-4331, 2019). However, little evidence exists to explain why such a gap exists in the help-seeking behaviors between White and racial-ethnic minority CCA. To address this knowledge gap, we conducted a systematic literature review to identify articles that have studied barriers in help-seeking for racial-ethnic minority CCA. A broad literature search across four databases was conducted (i.e., PubMed, PsycINFO, Education Resources Information Center, and Child Development and Adolescent Studies). The coding team identified 17 articles on help-seeking barriers for racial-ethnic minority CCA. A thematic analysis was used to narratively synthesize the help-seeking barriers identified across these 17 studies. Four themes emerged from our findings: logistical barriers, provider competence, ASD literacy, and cultural stigma. We also provided clinical recommendations for healthcare providers working with families with racial-ethnic minority CCA.

Humans

Impact of early nurse-led implementation of an intensive care unit diary following major trauma on quality of life: The QUALITRAU randomized controlled trial.

BACKGROUND: Survivors of major trauma often experience long-term impairments in health-related quality of life (HRQoL) and post-traumatic stress disorder (PTSD). Intensive care unit (ICU) diaries have been proposed to reduce psychological sequelae, but evidence remains conflicting and not specific to trauma patients. OBJECTIVE: To assess whether, in patients with major trauma, a nurse-led ICU diary implemented within the first 48&#xa0;h after trauma improves HRQoL at 1&#xa0;year vs. usual care. METHODS: The QUALITRAU randomized controlled trial was conducted in three ICUs of a French tertiary hospital. Adult patients with major trauma (Injury Severity Score&#xa0;>&#xa0;15) were randomized within 48&#xa0;h of admission to receive either an ICU diary combined with usual care or usual care alone. The primary outcome was HRQoL at 12&#xa0;months, assessed with the 4 domains of the WHOQOL-BREF questionnaire. Secondary outcomes included PTSD severity measured with the Impact of Event Scale (IES). Analyses were performed on an intention-to-treat basis. RESULTS: Between November 2014 and November 2016, 208 patients were randomized (101 intervention, 107 control), with primary outcome available for 121 (53 intervention, 68 control). Median age was 35&#xa0;years [IQR 25-51], 81% were men, and 63% had severe traumatic brain injury. At 12&#xa0;months, there were no differences between intervention and control groups in the WHOQOL-BREF domains (physical: 5.7 [IQR 4.6-11.4] vs 9.1 [IQR 4.6-13.1],P&#xa0;=&#xa0;0.16; psychological: 8.0 [IQR 6.7-13.3] vs 11.3 [IQR 6.7-13.3],P&#xa0;=&#xa0;0.08; social: 5.3 [IQR 4.0-14.7] vs 12.0 [IQR 4.0-14.7],P&#xa0;=&#xa0;0.10; environment: 8.0 [IQR 5.5-14.5] vs 12.0 [IQR 5.5-15.5], P&#xa0;=&#xa0;0.05). IES scores were also not different. CONCLUSIONS: Early implementation of nurse-led ICU diaries was not associated with improved long-term HRQoL or reduced PTSD symptoms in patients with major trauma. IMPLICATION FOR CLINICAL PRACTICE: These findings suggest that ICU diaries may need to be integrated into broader, multimodal rehabilitation strategies and may depend on factors such as timing, content, or patient characteristics.

Humans

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups.

BACKGROUND: Acute bipolar mania carries negative social and economic consequences. We investigated the comparative efficacy/response/acceptability of pharmacological interventions for acute bipolar mania, considering dose effects across different age groups. METHODS: We conducted a network meta-analysis (NMA) to search for randomized controlled trials (RCTs) comparing pharmacological interventions with one another or placebo in acute bipolar mania patients, indexed in PubMed/MEDLINE, Embase, Web of Science, and Scopus (from inception through 2025.12.24). Co-primary outcomes were change in manic symptoms/response/and acceptability. Tolerability/remission and rate of adverse events were secondary outcomes. Confidence-In-Network-Meta-Analysis was likewise appraised. RESULTS: 113 RCTs, encompassing 49 distinct treatment combinations, included 20,666 participants. Sensitivity analysis retaining only low-risk-of-bias studies and excluding outliers for possible effect modifiers indicated that risperidone 3&#xa0;mg/day(SMD&#xa0;=&#xa0;-7.57;95%C.I.&#xa0;=&#xa0;-8.25;-5.85); tamoxifen 160&#xa0;mg/day(SMD&#xa0;=&#xa0;-1.73;95%C.I.&#xa0;=&#xa0;-2.32;-1.13); rivastigmine 3&#xa0;mg/day(SMD&#xa0;=&#xa0;-1.13;95%C.I.&#xa0;=&#xa0;-1.06;-0.58); haloperidol 30&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.96;95%C.I.&#xa0;=&#xa0;-1.25;-0.75); valproate 750&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.76;95%C.I.&#xa0;=&#xa0;-1.48;-0.58); tamoxifen 40&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.75;95%C.I.&#xa0;=&#xa0;-1.41;-0.59); celecoxib 400&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.74;95%C.I.&#xa0;=&#xa0;-1.20;-0.38); paliperidone extended-release 12&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.62; 95%C.I.&#xa0;=&#xa0;-0.91;-0.32); olanzapine 15&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.59;95%C.I.&#xa0;=&#xa0;-0.60;-0.38); olanzapine 20&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.52;95%C.I.&#xa0;=&#xa0;-0.66;-0.38); risperidone 4&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.53;95%C.I.&#xa0;=&#xa0;-0.76;-0.29); allopurinol 600&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.54;95%C.I.&#xa0;=&#xa0;-0.67;-0.22); cariprazine 12&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.49;95%C.I.&#xa0;=&#xa0;-0.66;-0.33); risperidone 4.2&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.46;95%C.I.&#xa0;=&#xa0;-0.75;-0.17); lithium 1500&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.42;95%C.I.&#xa0;=&#xa0;-0.57;-0.28); ziprasidone 160&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.49;95%C.I.&#xa0;=&#xa0;-0.68;-0.31); asenapine 20&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.38;95%C.I.&#xa0;=&#xa0;-0.53;-0.22); haloperidol 8&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.34;95%C.I.&#xa0;=&#xa0;-0.63;-0.05); aripiprazole 15&#xa0;mg/day(SMD&#xa0;=&#xa0;-0.33;95%C.I.&#xa0;=&#xa0;-0.61;-0.06) outperformed placebo. Ziprasidone 160&#xa0;mg/day, celecoxib 200&#xa0;mg/day, asenapine 20&#xa0;mg/day, and asenapine 10&#xa0;mg/day proved more efficacious than placebo in children. No statistically significant differences were reported between treatments and placebo for response/remission/acceptability/tolerability, and manic/hypomanic switch. A meta-regression of efficacy effect sizes against the adapted AMSTAR-Plus content scores showed that larger SMDs were associated with lower AMSTAR scores, indicating lower study quality, warranting further caution for such large efficacy estimates. CONCLUSIONS: Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups.

Humans

Feasibility and acceptability of skills training in affective recovery (STAR) video and TextSTAR text message program for recent sexual assault survivors.

Background: Sexual assault (SA) affects more than 50% of women in the United States and is associated with elevated risk for impairing posttraumatic stress symptoms and substance, particularly opioid, misuse. Intervening following SA exposure could attenuate these risks.Objective: This study examined the acceptability and feasibility of a 17-minute video, Skills Training in Affective Recovery (STAR) and a 21-day text message program (TextSTAR), that were delivered in the acute post-SA period to prevent the onset or escalation of posttraumatic stress symptoms and substance misuse. The interventions provide psychoeducation about trauma, strategies to reduce fear and avoidance, suggestions to increase social support, and coping strategies for substance use.Method: Participants were 50 women age 18 or older who presented for a Sexual Assault Medical Forensic Exam (SAMFE) within seven days of a SA. Using a Sequential Multiple Assignment Randomized Controlled Trial (SMART) design, participants were randomized to receive the STAR video (n&#x2009;=&#x2009;25) or no video (n&#x2009;=&#x2009;25) at the SAMFE. Those who received the video answered questions about video acceptability immediately after viewing the video. At 1-week post-SAMFE, participants completed online questionnaires about substance use and posttraumatic stress; those above threshold on acute stress or opioid use (n&#x2009;=&#x2009;36) were randomized to TextSTAR (n&#x2009;=&#x2009;18) or no-text program (n&#x2009;=&#x2009;18). Participants completed weekly online surveys 2-4 weeks post-SAMFE about symptoms and text program acceptability.Results: Participants found STAR and TextSTAR at least moderately acceptable; 80% who received STAR found it extremely acceptable while 60-90% (depending on timepoint) who received TextSTAR found it at least moderately acceptable. Our ability to enroll 50 participants and retain 94% at 1 week and 90% at 4 weeks suggests the intervention trial is feasible.Conclusions: STAR and TextSTAR are acceptable and feasible brief interventions for recent sexual assault survivors.Trial registration: ClinicalTrials.gov identifier: NCT06456190.

Humans