Psychiatry Research

A systematic review and meta-analysis of sleep studies in schizoaffective disorder were conducted using published articles researched in major databases within the period from inception to December 1, 2025. The sleep parameters: total sleep time, sleep efficiency, sleep latency, wakefulness, REM time and percentage, REM latency, REM density, stage 1, 2, 3 and 4 sleep time and percentage, delta sleep time and percentage, of drug-free schizoaffective patients were analyzed and, where available, compared with case-control data of healthy controls, depressed unipolar patients and schizophrenic patients. Forty studies were identified in the systematic review. Nine case-control studies with 67 schizoaffective patients, 88 schizophrenic patients, 79 healthy controls and 131 depressed patients were included in the meta-analyses. The primary outcome was the standard mean difference. Data were fitted with a random-effects model. Publication bias assessment was checked by Egger's Regression and funnel plot asymmetry. Patients with schizoaffective disorder showed reduced total sleep time, increased sleep latency and wakefulness, along with reduced REM time and shortened REM latency, reduced stage 4 sleep time and percentage compared to healthy controls. Patients with schizoaffective disorder differed from depressed patients only for increased sleep latency, while they did not show any difference compared to patients with schizophrenia. SZA showed a non-significant trend (p=0.08) towards increased REM density compared to SCZ, suggesting the need to better clarify the role of REM density in mood and psychotic disorders.

Background Somatic and psychological symptoms like depression, anxiety, and trauma-related stress often co-occur, especially in young adults, a group facing major life transitions and increased vulnerability. These overlapping symptoms pose diagnostic challenges that traditional disorder-specific models capture poorly. Transdiagnostic and dimensional approaches may offer a more meaningful framework. However, population-based data on symptom patterns in young adults remains sparse. This study investigated the patterns of psychological and somatic symptoms among young adults from Switzerland and compares these results to findings from populations with different stress exposure histories: Ukrainians who fled to Switzerland, and Ukrainians living in different regions in Ukraine during the war. Methods We analyzed cross-sectional baseline data collected in spring 2024 as part of the Mental Health Assessment of the Population (MAP) studies, where we enrolled randomly selected young adults aged 18-24 from Switzerland, Ukrainian refugees in Switzerland, and Ukrainians residing in regions with different degrees of proximity to active war zones. We assessed somatic (PHQ-15) and psychological symptoms (PHQ-9, GAD-7, PCL-5) and explored symptom patterns using descriptive statistics, correlations, and k-means clustering. Results Psychological symptom severity showed highly consistent moderate-to-strong correlations with somatic symptoms (range: 0.53-0.69), across all young adult subgroups and disorders. Rather than identifying disorder-specific patterns, symptoms clustered by overall symptom severity, emerging in three clusters: (1) high symptom burden, (2) moderate symptom burden, and (3) low symptom burden clusters with elevated somatic, depressive, anxiety, and PTSD symptoms. The cluster structure was remarkably stable across Swiss, Ukrainian, and refugee subsamples, despite markedly different stress exposure histories. Conclusion Our results support a symptom-based, dimensional approach to understanding mental health in young adults and to better capture the complexity and co-occurrence of psychological and somatic symptoms in this age group. These findings further suggest that prevention and early detection strategies should more systematically integrate both psychological and somatic symptomatology.

Background: Narcolepsy is a debilitating sleep disorder caused by hypocretin deficiency. Aside from its role to induce wakefulness, hypocretin is linked to modulated appetite and metabolism, often resulting in weight gain. Study objectives: We aimed to unravel the comprehensive epidemiological connection between narcolepsy and major cardiometabolic outcomes. Methods: We analyzed cardiovascular and metabolic disease distribution in the FinnGen study. Using longitudinal electronic health records, we assessed associations between narcolepsy, cardiac/metabolic markers, and prescriptions for relevant drugs. Results: Our findings demonstrate significant associations between narcolepsy and metabolic traits (OR [95% CI] = 2.65 [1.81, 3.89]) as well as stroke (OR = 2.36 [1.38, 4.04]). Narcolepsy patients exhibit a less favourable metabolic profile, including higher glucose levels (OR = 1.1143 [1.0599, 1.1715]) and dyslipidaemia. This is supported by increased prescriptions of insulin (OR = 2.269 [1.46, 3.53]), simvastatin (OR = 2.292 [1.59, 3.31]), and metformin (OR = 2.327 [1.66, 3.25]), reflecting high metabolic disturbances. Furthermore, positive associations with antihypertensive and antiplatelet medications were observed, consistent with elevated cardiovascular risk. Conclusion: Taken together, our findings highlight the cardiometabolic burden in narcolepsy. This study enhances understanding of the metabolic and cardiovascular consequences of narcolepsy and offers timely guidance for effective disease control.

Background. Adolescence and young adulthood represent critical developmental stages during which mental disorders often emerge, with the potential to impede perceived quality of life. Spirituality (i.e., the search for the sacred) and self-regulation (i.e., intrinsic processes regulating emotions, thoughts, and behaviors) are recognized as protective factors for mental health. However, their dynamic interplay remains largely unexplored, particularly in real-life and in real-time among youths. This study, developed with the help of young partners, addresses this gap by investigating the longitudinal associations between spirituality, self-regulation, and mental health using an ecological momentary assessment (EMA) approach. Methods and analysis. We plan to recruit 120 adolescents and young adults (aged 16 to 20, expected attrition rate of 20%) from the community to complete a qualitative semi-structured interview assessing their beliefs, spiritual or religious activities, role models, and meaning in life. In addition, participants will take part in a multi-wave intensive longitudinal study. Trait-level assessments will be conducted at two time points, three months apart, to capture between-person differences. Additionally, to assess within-person dynamics, participants will complete EMA surveys four times daily over 10 consecutive days in two waves, also three months apart. Measures will include facets of spirituality (e.g., beliefs, meaning, collective consciousness), self-regulation (e.g., self-control, emotional regulation, impulsivity), as well as mental health indicators (emotional and behavioral symptoms) and quality of life. Qualitative data will be analyzed through a thematic analysis method, whereas quantitative associations will be assessed using Linear Mixed Models (LMM) and network analyses. Ethics and dissemination. Ethical approval has been obtained, and data collection begun in May 2025. Findings will be disseminated through open access peer-reviewed journals, conferences on adolescent mental health, and shared with practitioners, educators, and youth organizations. Results will also be made accessible to the general public. This study aims to inform personalized preventive and therapeutic interventions by elucidating real-time mechanisms linking spirituality, self-regulation, and mental health in youths.

BackgroundThe mechanisms underpinning associations between sleep and psychiatric conditions are poorly understood, partly due to challenges with longitudinal sleep studies outside the laboratory. Children and young people with rare genetic conditions caused by micro-deletions or -duplications (Copy Number Variants or CNVs) have increased risk of disrupted sleep and poorer neurodevelopmental (ND) outcomes. The Sleep Detectives study aims to investigate this by tracking behavioural and neurophysiological signatures of sleep health in young people with ND risk or ND-CNVs. To optimally achieve this, we have worked with families with ND-CNVs and charity partners to co-design our tools, methods, study protocol, and materials. MethodWe established a Lived Experience Advisory Group (LEAP) with nine parents and 13 children and young people with ND-CNVs, alongside representatives of UK charities Max Appeal and Unique. Together, the research team and LEAP co-designed two in-person family workshops in which we collected feedback on the acceptability of sleep monitoring devices, the design of bespoke cognitive tasks, and overall study protocol. Informal interviews and surveys were conducted with LEAP members and researchers, to enable the team to reflect and learn from their Patient/Public Involvement (PPI) experiences. ResultsKey outputs included pre-workshop invitation and briefing materials and insights that iteratively refined the main study design, including the need for flexibility to increase accessibility, selection of sleep devices, customisation of cognitive tasks, and choice of language in documents. The PPI process was highly valued by LEAP members, workshop attendees, and the research team. One investigator described the PPI work as "reinvigorating my love of research by helping me focus on science that matters". Participating families also established peer support networks. ConclusionsInvolving families affected by ND-CNVs in co-designing the Sleep Detectives study maximised opportunities for acceptability, accessibility and scalability. The research team gained inspiration and deeper understanding of the impact of ND-CNVs on families. Families gained awareness about research, established connections with each other and peer support, and were enthusiastic about future research involvement. This experience empowered families to engage more deeply with the research process and helped the PPI work to be more impactful and inclusive. Plain English summaryChildren and young people with rare genetic conditions caused by small deletion or duplication of genetic material are more likely to experience sleep difficulties such as insomnia, restless sleep, and tiredness. They also show an increased likelihood of neurodevelopmental conditions such as learning disability and autism, and mental health issues such as anxiety. The Sleep Detectives team wanted to explore how these genetic conditions affect childrens sleep, cognition and psychiatric health. To make sure that the project design was well suited to the children and young people that would be invited to participate, the team worked closely with families to design the study. Parents and caregivers of affected children and young people were invited to join a Lived Experience Advisory Panel (LEAP), together with charity representatives and Sleep Detective researchers, to co-design two hands-on workshops, and advise on study design. Children and young people and parents/caregivers attending the workshops tried out and provided feedback on tools and devices that the research team were developing. They also advised on the arrangements and support families might need whilst taking part, and on the study protocol. This collaborative approach helped ensure the study design was optimally suited for the recruitment and participation of children and young people and their families. This report documents our public involvement work for the Sleep Detectives study, illustrating the difference the partnership between researchers and families has made to the project, and the wider benefits for all concerned.

3,4-methylenedioxymethamphetamine (MDMA) has emerged as a potential treatment for post-traumatic stress disorder (PTSD), generating considerable enthusiasm in the field. However, rapidly changing evidence in a fast-moving field can be challenging to integrate. Here, we present a living systematic review and open-data meta-analytic resource on MDMA treatment for PTSD. In this initial release, six randomized controlled trials comprising 286 participants are included in the database. Our primary model uses inverse-variance random-effects meta-analysis of standardized mean differences on primary outcomes of PTSD. Compared to control conditions, MDMA showed a greater reduction in PTSD symptoms (Hedges' g = -0.71). Meta-regression on both the number of dosing sessions and cumulative dose showed that a higher number of dosing sessions and a higher cumulative dose was related to larger effects of MDMA. Treatment with MDMA as compared to placebo also resulted in higher response (risk ratio (RR) = 1.35) and remission (RR = 2.25) rates. Most studies included in the database had a low risk of bias according to Cochrane guidelines, though these fail to capture pertinent challenges in the field such as expectancy, functional unblinding, potential issues with study conduct, and safety. The current findings were assigned an overall low certainty rating using the GRADE approach. Together, this systematic review and meta-analysis suggests that MDMA-assisted therapy results in short-term decreases in PTSD symptoms across studies to date, though more trials are needed. This living systematic review, meta-analysis, database, and online dashboard (sypres.io) will continue to be updated as evidence emerges, providing a valuable, open, and transparent resource for researchers in a rapidly evolving field.

Introduction People with bipolar disorder (BD) and concurrent opioid use disorder (OUD) experience more severe clinical outcomes, including higher mortality, treatment complexity, and worse psychiatric symptoms, yet they are underserved due to a lack of tailored clinical guidelines and limited supporting research on competing treatment options. While pharmacological treatments for BD are well-established, their use varies widely across settings, and their effectiveness in individuals with co-occurring OUD is unclear. We propose parallel population-based studies to emulate randomized controlled trials to assess the comparative effectiveness of pharmacological treatment options for BD among people with OUD in British Columbia and Ontario, Canada, 2010-2023. Methods and analysis We propose emulating a series of parallel target trials using linked population-level health administrative data for all individuals aged 18 years or older diagnosed with both BD and OUD and who initiated treatments for BD between 1 January 2010 and 31 December 2023. All analyses will be conducted in parallel in British Columbia and Ontario. We propose a series of four successive target trial emulations, comparing (i) lithium versus non-antipsychotic mood stabilizers such as divalproex, lamotrigine, and valproic acid; (ii) lithium versus 2nd generation antipsychotics with mood stabilizing properties such as risperidone, olanzapine, aripiprazole, and quetiapine; (iii) lithium versus combination treatments such as lithium and divalproex, lithium and olanzapine, lithium and aripiprazole, lithium and quetiapine, divalproex and olanzapine, and olanzapine and quetiapine; (iv) lithium and valproate (LATVAL) versus lithium and olanzapine, lithium and aripiprazole, lithium and quetiapine, divalproex and olanzapine, and olanzapine and quetiapine. Incident user and prevalent new user analyses are planned for proposed target trials (i)-(iv), pending sufficient data. Stratified analyses will be conducted for BD-I, manic and depressive phases of BD illness. We propose an initiator analysis (intention-to-treat, conditional on medication dispensation) to determine the effectiveness of the treatments and per-protocol analyses to determine the efficacy of the treatments after dealing with treatment switching and recommended dose adjustment. The outcomes will include psychiatric acute-care visits (hospitalizations and emergency department visits), BD treatment discontinuation and all-cause mortality. Subgroup and sensitivity analyses, including cohort and study timeline restrictions, eligibility criteria modifications, and outcome reclassifications, are proposed to assess the robustness of our results. Executing analyses in parallel across settings using a co-developed protocol will allow us to evaluate the replicability of findings. Ethics and dissemination The protocol, cohort creation, and analysis plan have been classified and approved as a quality improvement initiative by the Providence Health Care Research Ethics Board and the Simon Fraser University Office of Research Ethics. Results will be disseminated to local advocacy groups, clinical groups and decision-makers, national and international clinical guideline developers, presented at international conferences, and published in peer-reviewed journals.

Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we characterised esketamine-induced mystical experiences in relation with clinical outcomes. We conducted a longitudinal observational study and systematically measured acute subjective effects in patients receiving esketamine for treatment-resistant depression after each administration across the induction phase. A total of 45 patients were included, from two independent centres, totalling 352 esketamine administrations. Principal Component Analysis (PCA) supported the validity of the Mystical Experience Questionnaire (MEQ-30) for assessing esketamine-induced subjective effects, with components recovering dimensions previously validated with classic psychedelics. Mystical experiences (MEQ-30 score above 60) occurred in 58% of patients, with high inter- and intra-individual variability in frequency, intensity, and phenomenology across sessions. Higher mean and peak MEQ scores were associated with greater improvement in Montgomery-Asberg Depression Rating Scale scores from pre- to post-treatment, whereas the intensity of dissociative or other non-mystical effects was not. Positive mood and mystical MEQ dimensions in particular predicted therapeutic outcomes. Baseline spirituality also significantly predicted treatment outcomes and peak MEQ scores in the first week of treatment. These findings add to the growing body of evidence suggesting that psychedelic-like mystical experiences may be associated to therapeutic efficacy, not only in classic psychedelic-assisted therapy, but also in esketamine treatment.

Background: Bipolar disorder (BD) is increasingly conceptualized as a heterogeneous condition with a neurodevelopmental phenotype (NDP) identifying a subgroup with early neurodevelopmental vulnerability and poorer clinical outcomes. Sensory processing (SP) abnormalities are a core feature of neurodevelopmental disorders but remain poorly characterized in BD and may reflect underlying neurodevelopmental liability. We examined whether NDP load is associated with specific SP alterations in euthymic BD patients and whether NDP-based stratification explains SP variability better than conventional BD subtype (BD 1/2). Methods: We assessed 102 euthymic BD patients and 45 healthy controls (HC) using the Adolescent/Adult Sensory Profile (AASP). NDP load (0-3) was computed from nine clinical variables grouped into neonatal, comorbidity, and neurodevelopmental clusters; a median split defined BD without NDP (BD) and BD with NDP (BD-ND). Associations between NDP load and AASP quadrants were analyzed using Spearman correlations with FDR correction. Group differences (BD, BD-ND, HC) were assessed using Welch ANOVA and post-hoc tests. Nested and multivariable linear regressions examined whether NDP classification explained SP variance beyond BD subtype, adjusting for age, sex, anxiety, and residual mood symptoms. Results: Higher NDP load correlated with greater low registration (rho=0.35, p<0.001, q=0.004), sensory sensitivity (rho=0.30, p=0.001, q=0.004), and sensation avoiding (rho=0.23, p=0.014, q=0.040), but not sensation seeking. BD-ND showed higher low registration, sensory sensitivity, and sensation avoiding than BD and HC (all qs<0.01). NDP classification explained more SP variance than BD subtype; with robust associations after adjustment. Conclusions: Sensory processing alterations in BD are dimensionally associated with neurodevelopmental load and more accurately captured by NDP-based stratification than diagnostic subtype. SP alterations may represent a transdiagnostic marker of neurodevelopmental liability within BD, supporting biologically informed stratification approaches.

Nighttime agitation (NA) is a prevalent and challenging phenomenon affecting people with dementia (PwD), often resulting in premature institutionalization. Yet, informal caregivers' perspectives on this phenomenon remain underexplored. We conducted 15 in-depth interviews with informal caregivers to gain insight into their experiences and reactions to NA. Thematic analysis identified seven sub-themes related to carers' experience and eight sub-themes concerning their reactions. These themes emerged across three levels, namely, PwD, informal caregiver and the environment. Most phenomena occurred at a dyadic level between PwD and informal caregiver, highlighting the potential of interventions targeting dyadic coping. Informal caregivers feel insufficiently supported when sleep disturbances co-occur with NA. They primarily rely on self-initiated strategies and learn by experience. Caregivers mention the need for more advanced knowledge and skills in reacting to co-occurrence of sleep disturbances with NA or systemic support in terms of dealing with emergencies. Caregivers also reflect extensively on the impact of challenging behaviors during the night on their mental and physical well-being. Notably, no non-pharmacological interventions for NA adequately address the themes identified in this study, highlighting the urgent need for integrative approaches and recognition of caregiver wellbeing as a core outcome, not a secondary consideration in interventions.

Background: The etiology and nosological status of seasonal affective disorder (SAD) as a specifier of depressive episodes versus a transdiagnostic disorder are the subject of debate. In this study, we investigated the underlying etiology of SAD and dimensional seasonality by examining their association with latitude and genetic risk for a range of traits, and investigated gene-environment interactions. Methods: This study included 12,460 adults aged 18-90 with a history of depression from the Australian Genetics of Depression Study. Regression models included predictors for latitude (distance from equator) and polygenic scores for eight traits; major depressive disorder, bipolar disorder, anxiety disorders, chronotype, sleep duration, body mass index, vitamin D levels, and educational attainment. Outcomes were SAD status and general seasonality score. Results: SAD was positively associated with latitude (OR[95%CI] = 1.05[1.03-1.06], padjusted<0.001), and there was nominal evidence of additive and multiplicative interactions between chronotype genetic risk and latitude (OR = 0.99[0.99-0.99], padjusted=0.381; OR=0.98[0.97-0.99], padjusted=0.489). General seasonality score was associated with latitude (IRR=1.01[1.01-1.01], padjusted 0.001) and genetic risk for major depressive disorder (IRR =1.02[1.01-1.03], padjusted<0.001), bipolar disorder (IRR=1.02[1.01-1.03], padjusted=0.001), anxiety disorders (IRR=1.03[1.01-1.04], padjusted<0.001), vitamin D levels (OR=0.89[0.80-0.95], padjusted=0.048), and educational attainment (IRR=0.97[0.96-0.99], padjusted<0.001). Conclusions: These findings enhance understanding of SAD etiology, highlighting contributions of psychiatric genetic risk and geographic measures on seasonal behavior, and support examining seasonality as a continuous dimension.

Abstract Background: Mental health services are shifting towards person-centred care based on collaboration and shared decision making. Yet evidence indicates that these approaches may not be consistently embedded in the assessment and management of risk or safety. Methods: We conducted a cross-sectional online survey to examine perceived barriers and enablers to shared decision-making in risk assessment and management with people living with severe mental illness. Questionnaire development and data analysis were guided by the Theoretical Domains Framework, a psychological framework used to identify and understand factors influencing behaviour change. Items were rated on a 5 point Likert scale. In total, 243 service users and mental health professionals completed the survey. Results: Most service users reported that risk or safety had been discussed with them, but only half felt involved in the risk assessment or management process. Two thirds reported not receiving a copy of their risk assessment or management plan. Service users strongly agreed that communication with professionals about risk and safety requires improvement, and that risk is a difficult and emotive topic to discuss. Professionals reported high motivation to involve service users but identified time constraints and service user related factors as key barriers. Principal component analysis identified four components: (1) motivation; (2) social influences and memory/decision making; (3) beliefs about consequences; and (4) team, environment and training factors. More experienced professionals reported fewer negative beliefs about consequences, such as concerns about causing distress or disengagement. Conclusion: Findings highlight the need for clearer communication, organisational support and targeted training to enhance shared decision-making in risk assessment and management practices.

BackgroundMajor depressive disorder (MDD), a leading cause of disability worldwide, exhibits substantial heterogeneity in treatment outcomes. Patients who do not respond to standard antidepressant therapy account for the majority of MDDs disease burden. Risk factors have been implicated in treatment response, including genes impacting on how antidepressants are metabolised. Yet, despite its clinical importance, risk factors for treatment-resistant depression (TRD) remain unexplored in low- and middle-income countries (LMIC). We used data from the DIVERGE study on MDD to investigate the risk factors of TRD in Pakistan. MethodsDIVERGE is a genetic epidemiological study that recruited adult MDD patients ([&ge;]18 years) between Sep 27,2021 to Jun 30, 2025, from psychiatric care facilities across Pakistan. Detailed phenotypic information was collected by trained interviewers and blood samples taken. Infinium Global Diversity Array with Enhanced PGx-8 from Illumina was used for genotyping followed by DRAGEN calling to infer metaboliser phenotypes for Cytochrome P450 (CYP) enzyme genes. We defined TRD as minimal to no improvement after [&ge;]12 weeks of adherent antidepressant therapy. We conducted multi-level logistic regression to test the association of demographic, clinical and pharmacogenetic variables with TRD. FindingsAmong 3,677 eligible patients, polypharmacy was rampant; 86% were prescribed another psychotropic drug along with an antidepressant. Psychological therapies were uncommon (6%) while 49% of patients had previously visited to a religious leader/faith healer in relation to their mental health problems. TRD was experienced by 34% (95%CI: 32-36%) patients. The TRD group was characterised by more psychotic symptoms and suicidal behaviour (OR=1.39, 95%CI=1.04-1.84, p=0.02; OR=1.03, 95%CI=1.01-1.05, p=0.005). Social support (OR=0.55, 95%CI=0.44-0.69, p=1.4x10-7) and parents being first cousins (OR=0.81, 95%CI=0.69-0.96, p=0.01) were associated with lower odds of TRD. In 1,085 patients with CYP enzyme data, poor (OR=1.85, 95%CI=1.11-3.07, p=0.01) and ultra-rapid (OR=3.11, 95%CI=1.59-6.12, p=0.0009) metabolizers for CYP2C19 had increased risk of TRD compared with normal metabolisers. InterpretationThere was an excessive use of polypharmacy in the treatment of depression while psychological therapies were uncommon highlighting the need for more evidence-based practice. This first large study of MDD from Pakistan uncovered the importance of culture-specific forms of social support in preventing TRD, highlighting opportunities for interventions in low-income settings. Pharmacogenetic markers can be leveraged to predict TRD.

AIM Older adults experiencing anxiety disorders, particularly those from minority ethnic backgrounds, are less likely to use formal mental health services compared to their younger counterparts. This UK multicultural qualitative study aimed to explore and compare beliefs underpinning coping strategies for anxiety among self-reporting White British, South Asian, African and Caribbean older adults, using Leventhal's Common-Sense Model of Self-Regulation. METHODS Individual semi-structured interviews were undertaken with 52 older adults aged 65 and over who self-reported (current or past) anxiety. Professional interpreters supported interviews with non-English-speaking participants (n=10). Eight public contributors collaborated on different aspects of the study. The Framework Method was used to manage and analyse the data. FINDINGS The study drew on the perspectives of 27 older adults with distressing anxiety and 25 with non-distressing anxiety. Across all cultural groups, participants adopted different strategies to manage anxiety, the most prominent of which were self-help strategies. Help-seeking behaviour was influenced by a complex interplay of factors not recognised by Leventhal's Common-Sense Model. Notably, older adults' salient identities, rather than their cultural backgrounds, influenced their selection of coping strategies. CONCLUSIONS Interventions that empower older adults to use self-help strategies more effectively can serve as acceptable adjuncts to formal therapy. Nevertheless, addressing barriers to formal help-seeking is essential, particularly among those with a perceived need to seek help. No one model can depict the complexity of coping behaviours. While applying Leventhal's Common-Sense Model yielded novel insights, it could not fully capture the motivational factors underlying participation in specific coping behaviours. To provide nuanced and accurate insights, cross-cultural research should acknowledge heterogeneity within groups rather than impose boundaries of purportedly homogeneous entities.

Introduction: The Nationwide Quality of Life Scale (NQLS) is a brief, mental-health focused quality of life (QoL) scale with seven items that are non-overlapping with symptom scales. We developed a parent version (P-NQLS), obtained national norms, and calculated psychometric properties for the P-NQLS. Methods: Parents (N=2251) of children aged 6-18 years who were representative of the U.S. population on key demographics completed the P-NQLS along with measures of depression, suicidality, internalizing, externalizing, and attention symptoms. We assessed the P-NQLS's factor structure through exploratory factor analysis (EFA) and evaluated its internal reliability and convergent validity. Age- and sex-specific norms were established using GAMLSS with BCPE distributions and P-spline smoothers, with percentile curves and tables (5th-95th) provided. Results: EFA suggested a one-factor solution for P-NQLS in the national sample. The scale showed good internal consistency (Cronbach's alpha=0.85). P-NQLS total scores (M=20.7, SD=4.7, range=0-28, higher scores indicate higher QoL) were negatively correlated (all p<.0001) with depression (Pearson's r=-0.47), suicidality (r=-0.50), internalizing (r=-0.43), externalizing (r=-0.41), and attention (r=-0.37) symptoms. P-NQLS scores declined steadily with age in both sexes, with the most pronounced decreases (3-5 points) observed at lower percentiles (5th, 10th), suggesting greater age-related decline among children with lower baselines. Females scored slightly higher than males across most ages and percentile levels, though the differences were within one point. Conclusions: The newly created P-NQLS, a 7-item parent-reported QoL scale with one underlying factor, demonstrates strong reliability and validity and has robust national norms for youth aged 6-18.

ImportanceBlood neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are entering clinical use in neurology as markers of neuroaxonal and astrocytic injury, but their utility in psychiatry is unclear. ObjectiveTo determine whether psychiatric diagnoses are associated with altered plasma NfL and GFAP levels. Design, Setting, and ParticipantsThis population-based study examined plasma NfL and GFAP among 47,495 participants from the UK Biobank (54.0% female; 93.5% White; mean [SD] age 56.8 [8.2] years) who provided blood samples and sociodemographic and clinical data between 2006 and 2010. Normative modeling was applied to assess associations between 7 lifetime psychiatric diagnostic categories and deviations from expected NfL and GFAP levels, while accounting for neurological diagnoses, cardiometabolic burden, and substance use. Data were analyzed between July 2025 and March 2026. Main Outcomes and MeasuresDeviations in plasma NfL and GFAP levels from normative predictions. ResultsRelative to the reference population, plasma NfL levels were higher among individuals with bipolar disorder (d=0.20; 95% CI, 0.03-0.37; p=0.03), recurrent depressive disorder (d=0.23; 95% CI, 0.07-0.38; p=0.009), and depressive episodes (d=0.06; 95% CI, 0.02-0.10; p=0.01), lower among individuals with anxiety disorders (d=-0.07; 95% CI, -0.12 to -0.02; p=0.008), but did not differ in schizophrenia spectrum, stress-related, or other psychiatric disorders. Plasma GFAP levels were not elevated in any psychiatric disorders. Variability in NfL levels was greater among individuals with schizophrenia spectrum disorders (variance ratio [VR]=1.30; p=0.005), depressive episodes (VR=1.06; p=0.006), and anxiety disorders (VR=1.08; p=0.005). Variability in GFAP levels was increased only in anxiety disorders (VR=1.08; p=0.01). Plasma NfL levels exceeding percentile-based normative thresholds were more common among individuals with schizophrenia spectrum disorders, bipolar disorder, recurrent depressive disorder, and depressive episodes. Neurological diagnoses, cardiometabolic burden, and substance use were associated with plasma NfL and GFAP levels. Conclusions and RelevanceThis study provides population-level evidence of plasma NfL elevation in bipolar and depressive disorders and increased variability in schizophrenia spectrum, bipolar and depressive disorders, supporting its potential as a biomarker in psychiatry and informing its ongoing neurological applications. Plasma GFAP levels, in contrast, were largely unaltered across psychiatric disorders. Key PointsO_ST_ABSQuestionC_ST_ABSAre plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels altered in psychiatric disorders? FindingsIn this cohort study including 47,495 individuals, normative modeling revealed that plasma NfL levels were elevated in bipolar and depressive disorders, whereas plasma GFAP levels were not elevated in any psychiatric disorder. Plasma NfL levels also showed higher variability in schizophrenia spectrum, bipolar, and depressive disorders. MeaningPlasma NfL shows distinct alterations in schizophrenia spectrum and affective disorders, supporting its further investigation as a biomarker in clinical psychiatry and highlighting the need to consider psychiatric comorbidity in neurological applications.

Background: Previous evidence suggests that higher body size is associated with bipolar disorders, however, whether this association is causal remains uncertain. Interpretation is further complicated by heterogeneity across age, variation in clinical presentation, and potentially distinct underlying aetiologies. Aims: To determine whether body size exerts heterogenous causal effects on bipolar disorder subtypes and symptom profiles. Methods: By leveraging genetic instruments that differentiate effects at different life stages, summary-level univariable and multivariable Mendelian randomisation (MR) analyses were used to estimate how age-specific body size relates to adult psychiatric and symptomatic bipolar features; major depressive disorder (MDD), depressive symptom scores, subthreshold mania symptoms, bipolar disorder, bipolar type I and bipolar type II. Genetic instruments derived from genome-wide association studies (GWASs) for adult body mass index (BMI) (n= 681,275), childhood body size (n= 453,169) and mid-to-later life body size (n= 453,169) served as proxies for prepubertal and adult BMI measures. Results: In univariable MR, higher genetically proxied adult BMI increased the odds of MDD (odds ratio (OR) = 1.13, 95% CI 1.09-1.16), subthreshold mania (OR = 1.09, 95% CI 1.0-1.19)), and depressive scores (Beta = 0.07, 95% CI 0.05-0.09). There was little evidence that childhood body size had an effect on any outcome. Robust evidence suggested bipolar disorder and MDD increased adult BMI in our reverse univariable analyses. Using multivariable MR, robust evidence indicated that increased adult body size after accounting for childhood body size increased the odds of MDD, subthreshold mania and depressive scores. Conclusions: Body size may exert different causal effects on bipolar disorder depending on age and symptoms, with detrimental effects occurring during adulthood. Weaker evidence suggested varying effects across bipolar subtypes. Triangulation of findings and higher powered GWASs to detect symptom-specific genetic variants are required to explore whether body size contributes to distinct aetiologies across bipolar patients, informing the identification of novel and personalised treatment targets.

Objectives: The primary aim of this study was to assess the feasibility of delivering an adapted problem-solving skills (PSS) intervention by quantifying the recruitment, follow-up and completion rates using a brief problem-solving intervention for people with a mental health diagnosis in two Polish prisons. Design: IAPPS is an open, multi-centred, parallel group feasibility randomised controlled trial (RCT). Setting: Two prisons in Poland. Participants: Men in custody aged 18 years and older, having a mental illness and living within the prison therapeutic unit. Interventions: The intervention consisted of an adapted PSS skills intervention plus care as usual (CAU) or care as usual only. Delivered in groups of up to five people in 1.5-hour sessions over the course of two weeks. Main outcome measures: Primary outcomes - rate of recruitment, follow-up, and feasibility to deliver the intervention. Secondary outcomes included measures of depression, general mental health, and coping strategies. Results: 129 male prisoners were screened, 64 were randomly allocated, with a mean age of 53.5 years (SD 14, range 23-84). 59 (95%) prisoners were of Polish origin. Our recruitment rate was 48%. There was differential follow up with those in the intervention group less likely to complete the post-test battery versus those who received care as usual. Outcome measures were successfully collected at both time points. Conclusions We were able to recruit, retain and deliver the intervention within the prison setting; some logistical challenges limited our assessment of intervention engagement. Our data helps to demonstrate how use of the RCT study design can be implemented and delivered within the complex prison environment. Trial registration number ISRCTN 70138247, protocol registration date May 2021

Introduction Experiential acceptance refers to the capacity to be open to internal experiences without attempting to change or avoid them. Although acceptance is a core emotion regulation strategy within mindfulness- and acceptance-based interventions (MABIs) and a protective factor for mental health, its conceptualization and implementation remain unclear and ambiguous. The aim of this study was to clarify and develop a comprehensive model of accepting anxiety. Method Twenty-six participants from a non-clinical sample with prior experience in MABIs took part in semi-structured interviews exploring their experience of accepting anxiety. Data collection and analysis followed the principles of Grounded Theory to generate a data-driven model of the acceptance process. Results We identified a five-stage dynamic model involving distinct processes: (Stage 1) observing through the body with attentional focus on interoceptive experience; (Stage 2) identifying and acknowledging anxiety; (Stage 3) validating and normalizing the experience through validation and self-compassion; (Stage 4) not reacting characterized by decentering and nonreactivity; and (Stage 5) staying with the experience via exposure. We also identified facilitating factors that support engagement in the acceptance process. Conclusion These findings refine the understanding of acceptance as a multidimensional emotion regulation process by highlighting an active dynamic involving multiple mechanisms underlying the acceptance of anxiety. This model provides a framework for developing more targeted clinical interventions and for investigating individual and contextual variability in these subprocesses.

Schizophrenia (SCZ) and type 2 diabetes mellitus (T2DM) are common comorbid disorders that severely impair patient prognosis and quality of life. This study aimed to explore the association between the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and MTHFR promoter methylation in patients with comorbid SCZ and T2DM. A total of 120 participants were enrolled from Liaocheng Fourth Peoples Hospital between January 2025 and June 2025, comprising 30 subjects in each of the four groups: SCZ group, T2DM group, SCZ-T2DM comorbid (SCZ+T2DM) group, and healthy control (CTL) group. Corresponding primers were designed for genetic analysis, and methylation-specific PCR (MSP) was performed to detect the methylation level of the MTHFR promoter. Genotype distribution of the MTHFR C677T polymorphism was consistent with Hardy-Weinberg equilibrium (HWE) (p>0.05). The C677T polymorphism was significantly associated with an elevated risk of SCZ and T2DM comorbidity (p<0.05). Notably, the methylation rate of the MTHFR promoter in the SCZ+T2DM group (95.00%) was not significantly higher than that in the CTL group (90.00%) (p>0.05). In conclusion, the MTHFR gene may serve as a susceptibility gene for SCZ-T2DM comorbidity, whereas MTHFR promoter methylation is not associated with the pathogenesis of this comorbid condition. These results indicate that genetic variation in MTHFR, rather than promoter methylation, contributes critically to the comorbidity of SCZ and T2DM in the Han Chinese population. Our findings may provide novel molecular insights into their shared pathophysiology and inform future clinical strategies for patients with this complex phenotype.