Psychiatry Research

The COVID-19 pandemic had substantial impact on healthcare systems across the globe, including psychiatric services. Use of electroconvulsive therapy (ECT), a lifesaving intervention for severe mental illness, was reported to have declined during the pandemic in several countries, but nationwide data remain scarce. Using nationwide data from the Danish National Patient Register, we examined all ECT treatments administered in Denmark from September 2019 to May 2025. Weekly treatment numbers were visualized across the three national COVID-19 lockdowns to descriptively assess changes in ECT use. A notable reduction in ECT treatments was observed in the weeks preceding and during the first lockdown (March 11 to May 18, 2020). A post-hoc estimation indicated approximately 1,366 "missed" treatments during the initial pandemic phase in 2020. When these were added to the 27,033 treatments delivered in 2020, the adjusted total approximated annual treatment volumes in 2019 and 2022, suggesting a temporary disruption rather than sustained decline. In contrast, ECT activity during the second and third lockdowns appeared largely unaffected. These findings suggest that ECT provision in Denmark was temporarily reduced during the initial phase of the pandemic but remained resilient thereafter. In the case of a future pandemic, safeguarding timely access to ECT--particularly in early phases-- should be prioritized given its critical role in the treatment of severe mental illness.

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.

BackgroundUp to one-third of medical inpatients experience clinically relevant mental distress, yet many remain untreated. Stepped and collaborative care (SCC) models may improve access to mental health care, but predictors of service uptake are unclear. We examined patient- and ward-level predictors of psychosomatic-psychiatric consultation (PPC). MethodsWe analyzed data from SomPsyNet, a stepped-wedge cluster randomized trial targeting SOMatic inpatients across three Swiss tertiary hospitals, to prevent PSYchosocial distress by a care NETwork. Analyses focused on inpatients screening positive for mental distress. Multiple-imputed logistic regressions assessed predictors of four sequential service-use stages: PPC considered, offered, accepted, and received. ResultsAmong 589 distressed patients, 93.9% were offered PPC, 63.1% accepted, and 83.9% of acceptors received PPC, yielding a 50% overall receipt rate. Patients without Swiss citizenship showed higher odds of acceptance (odds ratio [OR]=1.82 [1.10, 3.00]) and eventual receipt (OR=1.62 [1.01, 2.62]). Being in a Geriatric ward facilitated PCC uptake, while patients from gynecology showed reduced progression through the care pathway. Age, gender, income, education, marital status, and living arrangement showed no statistically robust associations. ConclusionsAlmost two-thirds of mentally distressed medical hospital inpatients accepted an offered PPC, indicating high acceptability. About half ultimately received a consultation, highlighting substantial attrition along the SCC pathway. Ward specialty and nationality were key determinants of PPC uptake. These findings suggest that proactive, ward-oriented consultation-liaison models embedded in routine inpatient care may improve timely and equitable access to mental healthcare, including for migrant and minority patients who are otherwise less likely to access such care. HighlightsO_LIPsychosomatic-psychiatric consultation pathway of medically hospitalized inpatients C_LIO_LI63% accepted such a consultation when offered; overall 50% reached receipt. C_LIO_LINon-Swiss nationality increased odds of acceptance (OR 1.8) and receipt (OR 1.6). C_LIO_LIPatients at geriatrics wards showed higher, at gynecology wards lower transitions. C_LIO_LIResults support low-threshold, ward-oriented consultation-liaison models. C_LI

BackgroundAnorexia nervosa (AN) is a severe psychiatric disorder associated with profound malnutrition, multisystem medical complications, and one of the highest mortality rates among mental illnesses. Despite decades of research into its biological and neurocognitive mechanisms, effective pharmacological treatments remain limited. While systematic reviews synthesize results from published studies, clinical trial registries offer a complementary perspective by capturing ongoing research efforts, discontinued studies, and emerging therapeutic strategies that may not yet be reflected in the published literature. ObjectiveThis study aimed to characterize the landscape of clinical research in AN by systematically analyzing studies registered on ClinicalTrials.gov. MethodsWe conducted a structured analysis of studies registered on ClinicalTrials.gov related to AN. Trial characteristics, including study design, intervention type, phase classification, geographic distribution, and recruitment status, were extracted and analyzed using an automated text-based classification pipeline. ResultsNearly 400 studies investigating AN were identified over the past 25 years. Approximately 71% were classified as interventional studies; however, a large proportion were not associated with conventional clinical trial phases, suggesting that many registered trials correspond to mechanistic or exploratory investigations rather than therapeutic development programs. The geographic distribution of studies revealed a strong predominance of North America and Western Europe. A substantial proportion of trials were terminated or discontinued, highlighting the significant challenges associated with conducting interventional studies in this population. Observational studies generally included larger sample sizes than interventional trials. ConclusionsRegistry-based analyses provide valuable insights into the evolving landscape of clinical research in AN. Despite considerable scientific activity, important gaps remain between mechanistic knowledge and the development of therapeutic interventions. Understanding these gaps may help inform future translational research strategies aimed at improving treatment options for this severe disorder.

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.

BackgroundWhile growing evidence implicates sleep-wake and circadian rhythm disturbances (SCRDs) in the onset and course of mood and psychotic disorders, longitudinal studies using objective measures are limited. This clinical cohort study examined whether actigraphy-derived SCRDs (sleep duration, timing, and efficiency) predicted transition to (i) any full-threshold mental disorders; and then specifically: (ii) full-threshold bipolar or psychotic disorders or (iii) other full-threshold (i.e. depressive or anxiety) disorders, in youth accessing mental health care. MethodsActigraphy monitoring was completed for 5-23 days in 250 participants (aged 12-30) presenting to youth-focused early intervention services in Sydney, Australia. Participants were followed longitudinally as part of the Optymise cohort for 6+ months (up to 8 years; median 2.5 years). Logistic regression and Cox proportional hazard models estimated associations between SCRDs and illness progression, after controlling for relevant baseline clinical and demographic covariates (e.g., age, sex, social and occupational functioning, mania-like and psychotic-like experiences, medication use). ResultsLonger sleep duration at baseline predicted higher odds of transition (OR = 2.23 [95%CI = 1.38-3.74]), and shorter time-to-transition (HR = 2.05 [95%CI = 1.23-3.40]) to full-threshold bipolar or psychotic disorders. This effect remained significant after controlling for clinical covariates. Later sleep midpoint predicted transition to any full-threshold mental disorder (OR = 1.46 [95%CI = 1.02-2.17]) at the uncorrected significance level. ConclusionsExcessive sleep duration may represent an early marker of vulnerability for progression to severe mental illness. Findings support the prognostic utility of objective measures of SCRDs to guide indicated prevention and early intervention.

IntroductionNational trends in youth suicide risk may mask significant regional variations within a country. This article attempts to account for spatio-temporal trends through a comparative analysis across South America and Europe. This paper analyzes the spatiotemporal patterns in suicide mortality among young people (10-29 years) in Argentina, Chile, Spain, and Uruguay during the period 1997-2021. MethodsOfficial data from vital statistics and population censuses of the four countries were analyzed. Spatiotemporal clusters were detected using Poisson-based scan statistics. Sociodemographic characteristics of high-and low-mortality clusters were compared with the rest of each country using Kruskal-Wallis and Wilcoxon tests. ResultsWith the exception of Chile, each country showed the emergence of spatiotemporal suicide clusters extending through 2021. Indicators of social fragmentation and lower socioeconomic status were most consistently associated with the formation of high-risk youth suicide clusters. ConclusionRecent national increases in youth suicide rates appear to be concentrated in specific sub-national regions, underscoring the need to target resources toward improving living conditions and mental healthcare access for young people in these areas.

BackgroundPoor patient retention and family engagement compromise the effectiveness of coordinated specialty care (CSC) for first-episode psychosis (FEP). This mixed methods study aimed to identify program-level characteristics (CSC fidelity and engagement strategies) associated with patient retention and family engagement in Massachusetts CSC programs. MethodsPrimary outcomes were rates of patient retention and family engagement ([&ge;]1 evidence-based family intervention session), based on CSC program census (October 2022 - September 2023). Quantitative analyses explored program characteristics (EPINET Program-Level Core Assessment Battery) and fidelity ratings (Massachusetts Psychosis Fidelity Scale) as predictors using t-tests or univariate linear regressions. Thematic analysis of program interviews compared patient and family engagement strategies employed by high versus low performing programs. ResultsAcross nine programs, mean patient retention was 86% (range: 58-97%) and family engagement was 40% (range: 12-100%). Higher fidelity to evidence-based services (e.g., individual therapy, family intervention, and supported education/employment) was significantly associated with both outcomes (p<.05; R2 range: .51-.72). Mixed-methods analysis showed that high performing programs used case management-related supports to meet service users practical needs. Factors associated with higher patient retention included having comprehensive intake assessments, provider visits during hospitalization, and periodic treatment reviews. Programs that conducted benefits counseling and proactively recommended family services as standard care had higher family engagement. ConclusionsHigher fidelity CSC programs had better patient retention and family engagement. Case management-related supports addressed treatment barriers. Strategies designed to strengthen therapeutic alliance and goal alignment may promote patient engagement, while family engagement may benefit from proactive recommendation of family intervention.

ObjectiveDespite recommendations that young people at clinical high risk (CHR) for psychosis receive stepped treatment, few programs have published details of their clinical models or outcomes. This study describes the preliminary effectiveness of a risk calculator-informed stepped care model used at the Yale PRIME Clinic, a specialized outpatient clinic for young people at CHR. MethodsSeventy-one individuals (ages 12-25) at CHR enrolled in Yales PRIME Clinic during the first four years of the treatment program. Participants completed clinical assessments at six timepoints over two years of treatment within a care model informed by an empirically grounded psychosis risk calculator. Linear mixed-effect models were fit to examine changes in clinical symptoms over time, and sensitivity analyses evaluated differences in clinical trajectories between completers and non-completers. ResultsIndividuals engaged in treatment demonstrated significant and sustained improvements in positive, negative, general, disorganized, and depressive symptoms. Improvements in positive symptoms emerged by 6 months and continued to improve across most subsequent timepoints (6, 12, and 24 months). Pattern mixture analyses suggested that clinical trajectories did not significantly differ between completers and non-completers, though non-completers possessed more heterogeneous trajectories. ConclusionsA stepped care model informed by individualized risk calculator scores was feasible for delivery in a specialized outpatient setting, and was associated with broad symptom improvement for young people at CHR. Further controlled studies with blinded raters are needed to further confirm the efficacy of stepped care models and isolate the active components of treatment. HighlightsO_LIParticipants at clinical high risk for psychosis experienced significant reductions in attenuated psychotic symptoms and improvements in mood while enrolled in a risk-calculator-informed stepped care treatment model. C_LIO_LIParticipants who disengaged from treatment did not have significantly different clinical trajectories than those who remained in care. C_LIO_LIThe results suggest preliminary evidence for the feasibility of implementing a risk-calculator-informed stepped care model. C_LI

BackgroundLight plays a critical role in mental health, as the primary input to the circadian system, which regulates mood, energy, and the sleep-wake cycle. Altered light sensitivity is a potential mechanism in circadian-associated mental disorders. MethodsActigraphy-derived sleep, physical activity, and circadian rhythm correlates of the pupillary light reflex were explored in young people with emerging mental disorders. Participants were 27 healthy controls (Mean age=25.67 {+/-} 2.83, 52% female) and 155 young people from the Neurobiology Youth Follow-up Study (Mean age=25.48 {+/-} 5.65; 60% female), recruited from an early intervention mental health service. 32% of the latter group were re-assessed over 12 months. Pupil constriction, average and maximal constriction velocity, and constriction latency were recorded by the PLR-3000 monocular pupillometer in response to dim (~10 lux) and bright (~1500 lux) pulses. ResultsCompared to healthy controls, young people with emerging mental disorders had a smaller change in pupil diameter (p=0.037) and a slower maximal constriction velocity (p=0.018) in response to dim light. In the full sample, decreased dim light sensitivity was correlated with later timing of actigraphy-derived sleep midpoint. Within the clinical cases, increased genetic risk for bipolar disorder was correlated with increased dim light sensitivity, and higher insomnia clinical scores were correlated with decreased dim light sensitivity. Pupillometry measures were stable across time and seasons. ConclusionAltered light sensitivity may be associated with the emergence of mood disorder in young people and with altered sleep-wake timing.

ImportanceLarge language models (LLMs) have demonstrated diagnostic potential in several medical specialties, but their application to psychiatry - where diagnosis relies heavily on clinical judgment, narrative interpretation, and reasoning under uncertainty - remains insufficiently evaluated. ObjectiveTo evaluate diagnostic accuracy and clinician-judged reasoning quality of multiple large language models using psychiatric case vignettes. DesignMixed-methods evaluation study of diagnostic accuracy across four LLMs using 196 psychiatric case vignettes (135 published and 61 novel). Clinical reasoning quality was evaluated on a randomly selected subset of 30 vignettes using structured clinician ratings along two reasoning dimensions. The highest-performing model was illustratively compared with psychiatry trainees on the same subset. Diagnostic correctness for the full vignette set was assessed by a separate adjudicator LLM. SettingPublicly available model interfaces, December 2025. ParticipantsFive board-certified psychiatrists evaluated model-generated clinical reasoning. Two psychiatry residents served as the illustrative human comparison. Main Outcomes and MeasuresDiagnostic accuracy and clinician-rated clinical reasoning quality. Diagnostic accuracy was assessed using top-1 accuracy, top-5 accuracy, recall@5, and mean reciprocal rank based on ranked lists of five differential diagnoses per vignette. Clinical reasoning quality was assessed using two 5-point Likert scales adapted from the American Council of Graduate Medical Education Psychiatry Residency Milestones, evaluating data extraction and diagnostic reasoning. ResultsAcross 196 psychiatric case vignettes, Claude Opus 4.5 (Anthropic) achieved the highest diagnostic accuracy (top-1 accuracy, 0.638; top-5 accuracy, 0.801; recall@5, 0.731; mean reciprocal rank, 0.710) and clinician-rated reasoning scores. Higher clinician-rated diagnostic reasoning quality was strongly associated with diagnostic correctness in mixed-effects logistic regression analyses ({beta} = 1.80; p < 0.001), corresponding to an approximately six-fold increase in odds of a correct diagnosis per 1-point increase in reasoning score. In an illustrative comparison, diagnostic accuracy of Claude Opus 4.5 fell within the range observed for psychiatry trainees. Conclusions and RelevanceLLMs demonstrated high diagnostic accuracy and generated clinical reasoning that clinicians judged to be largely coherent and safe. Diagnostic reasoning quality was more strongly associated with diagnostic correctness than data extraction quality, underscoring the importance of evaluating reasoning alongside accuracy when assessing LLMs for clinical decision support in psychiatry. Key PointsO_ST_ABSQuestionC_ST_ABSCan multiple large language models accurately diagnose psychiatric conditions and generate diagnostic reasoning that clinicians judge as coherent, safe, and clinically meaningful? FindingsAcross 196 psychiatric case vignettes, four large language models demonstrated high diagnostic accuracy. In a clinician-evaluated subset of 30 vignettes, model diagnostic accuracy fell within the range observed for psychiatry residents. Clinicians judged model-generated diagnostic reasoning to be largely coherent and safe. Higher clinician-rated reasoning quality was strongly associated with diagnostic correctness, independent of data extraction quality. MeaningEvaluating diagnostic reasoning, in addition to accuracy, may be important when assessing large language models for potential clinical decision support in psychiatry.

BackgroundSuicidal ideation (SI) is a major global concern, yet its dynamic interplay with other symptoms remains poorly understood. ObjectiveTo identify symptoms that co-fluctuate with or temporally precede SI to improve warning signal detection and intervention. MethodsLongitudinal data from three Dutch psychiatric cohorts with lifetime internalizing disorders (16 waves from April 2020 until February 2022) were collected during the COVID-19 pandemic. We analyzed depressive, happiness, anxiety, loneliness, worry symptoms, and COVID-19-specific items only in those participants with SI fluctuations. Dynamic Time Warping (DTW) quantified within-person similarity between symptom trajectories and SI, and results were aggregated at group level. FindingsThe 307 participants (mean age 44.8 years; 61.6% female) showed increasing SI over time (p < .001). SI aligned with four depressive symptoms (i.e., sad mood, low self-esteem, low interest, and reduced happiness), two anxiety-related symptoms (i.e., fear of losing control, faintness), feeling abandoned, and overwhelming worrying. In directed DTW analysis, sad mood, hypersomnia, worrying about projects, and numbness/tingling showed significant temporal precedence before SI. ConclusionSI is embedded in a broad symptom network beyond depression. These results underscore the value of time-sensitive, idiographic monitoring using tools like DTW to capture the person-specific temporal pathways through which SI emerges and intensifies. Clinical implicationsThis study suggests a core group of affective, cognitive, and interpersonal symptoms that could serve as informative signals for evaluating changes in SI and may represent actionable targets for intervention. Summary BoxO_ST_ABSWhat is already known on this topic?C_ST_ABSO_LISuicidal ideation (SI) is a dynamic phenomenon, yet traditional research often relies on static, group-level averages that do not capture individual fluctuations. C_LIO_LIWhile SI is linked to depression, it can emerge independently through complex interactions with other affective and interpersonal states C_LI What this study adds?O_LIThis study identifies a set of affective, cognitive, and interpersonal symptoms, sad mood, overwhelming worry, and feelings of abandonment, that significantly co-fluctuate with SI over weeks and months. Additionally four specific "leading" symptoms, sad mood, hypersomnia, worrying about projects, and somatic numbness, were found that precede increases in SI. C_LI How this study might affect research, practice or policy?O_LIThe identified co-fluctuations and precursors serve as informative "(early) warning signals" that can improve individual risk stratification and clinical monitoring and may represent targets for intervention. C_LIO_LIThe results support a shift toward network-based models in suicidology, emphasizing the need for time-sensitive monitoring to capture the complex and dynamic nature of suicidality. C_LI

ObjectiveTo analyze the structure of mental disorders in children in the outpatient practice of a specialized mental health center for optimization of care organization for this patient category. MethodsA retrospective analysis of medical records of 23 children (out of 44 patients) at the Insight Mental Health Center (Dushanbe, Tajikistan) was conducted for the period from December 9, 2025, to January 8, 2026. Diagnosis was performed according to ICD-10 criteria using standardized instruments: M-CHAT-R, ADOS-2, and ADI-R for autism spectrum disorder (ASD); SNAP-IV for attention deficit hyperactivity disorder (ADHD); CGI; and pediatric versions of PHQ and GAD. ResultsChildren accounted for 52% of all patients. Primary school-age children (7-12 years) predominated at 43.5%. Disorders of psychological development (F80-F89) dominated the nosological structure at 82.6%, with ASD comprising 56.5%. ADHD was diagnosed in 30.4% of cases. Comorbidity was registered in 47.7% of patients. ConclusionThe structure of pediatric psychiatric pathology is characterized by a predominance of developmental disorders and high comorbidity levels, justifying the need for a multidisciplinary approach.

OBJECTIVEOpioid misuse exacts a tremendous toll on society. Mindfulness-Oriented Recovery Enhancement (MORE) is an efficacious treatment for opioid misuse. Yet, the cost-effectiveness of this intervention remains unknown. METHODSCost-effectiveness and cost-benefit analyses of a randomized clinical trial with enrollment of 250 adults with chronic pain prescribed long-term opioid therapy who were misusing opioids. Participants were randomized to MORE (training in mindfulness, reappraisal, and savoring positive experiences) or supportive group psychotherapy across 8 weekly 2-hour groups. Incremental cost-effectiveness ratios (ICER) and benefit-to-cost ratios (BCRs) were computed using the primary outcome of opioid misuse at 9-month follow-up, as assessed by a composite measure based on self-report, clinical interview, and urine screen. RESULTS250 randomized patients (64.0% female) had an average age of 51.8 years (SD=11.9), were mostly taking oxycodone or hydrocodone (69%), and had mean morphine equivalent opioid dose of 101.0 (IQR=74) mg. At 9-mo. follow-up, the difference in the probability of having a positive Drug Misuse Index (DMI) rating was 0.24 (0.54 for MORE participants vs. 0.78 for controls). The ICER of MORE relative to supportive psychotherapy was $116.3 per averted case of opioid misuse, $8.9 per life-year, and $8.0 per quality-adjusted life-year. MORE is cost-saving vs. supportive psychotherapy after adjusting for healthcare costs. Excluding all benefits associated with averting fatal overdoses results in a BCR of 84.2. CONCLUSIONSGiven MOREs cost-effectiveness, private and public payers should consider disseminating this evidence-based therapy broadly across the nation to reduce mortality and morbidity associated with the ongoing opioid crisis. HIGHLIGHTSO_LIMindfulness-Oriented Recovery Enhancement (MORE) substantially reduced opioid misuse among adults with chronic pain on long-term opioid therapy. C_LIO_LIMORE was highly cost-effective vs. supportive psychotherapy, costing $116 per averted opioid misuse case, and MORE was cost saving when accounting for healthcare costs associated with opioid misuse. C_LIO_LIFindings suggest wide dissemination of this evidence-based treatment could yield major healthcare and other economic benefits in addressing the opioid crisis. C_LI

Background Negative and stigmatizing attitudes towards people suffering from mental disorders among healthcare providers often act as a barrier to mental healthcare access. To assess these attitudes in primary care physicians (PCPs), a robust, culturally tailored psychometric tool is crucial. This study aimed to translate and psychometrically validate the MICA-4 to assess negative attitudes among PCPs in Pakistan. Methods We recruited two independent samples of PCPs (n=191, n=329) using non-probability sampling. Three bilingual mental health professionals forward-translated the scale, which was then independently reviewed and back-translated. Cognitive interviews were conducted (n=15 PCPs) to assess comprehension and clarity, for the final version to be used in the study. EFA was conducted on Sample 1 to examine the underlying factor structure of the Urdu MICA-4 items. CFA was then performed on Sample 2 to cross-validate the factor structure identified in Sample 1. Internal consistency and convergent validity were also assessed. Results A three-factor solution was retained, including Views (seven items), reflecting clinicians general evaluative perspectives toward mental illness and professional roles; Stereotypes (five items) representing generalized beliefs and disclosure-related concerns regarding individuals with mental illness, and Stigma (three items) capturing social distancing and perceived threat-related attitudes. The Comparative Fit (CFI = .958) and the Tucker-Lewis Index (TLI = .946) indicated good fit. Three items (9, 13, and 12) were removed due to weak loadings (< .40). Composite reliability ({omega}) indicated adequate internal consistency for the Views ({omega} = .70) and Stereotypes ({omega} = .74) factors, and lower for stigma ({omega} {approx} .53). Convergent validity was modest (.40 to .44). Conclusion The findings support the cautious use of Urdu MICA-4 in Pakistani primary care settings. The variability in the factor structure of the scale across cultures raises a practical implication for its dissemination. When item-level instability repeatedly emerges across contexts, permitting limited, evidence-based refinement may strengthen measurement stability and comparability, as well as its reliability in diverse healthcare settings.

IntroductionDepression is highly prevalent among young adults worldwide. While research links health behaviours, such as dietary intake, to depression, few studies have examined these associations among young adults in low- and middle-income countries, including South Africa. This study investigated whether dietary intake was associated with an increased risk of depression in a cohort of young South African adults, aged 20-30 years, as part of the Global burden of disease Lifestyle And mental Disorder (GLAD) project. MethodsThis five-year prospective cohort study was conducted in the North West Province of South Africa in accordance with the GLAD project protocol (DERR1-10.2196/65576). Dietary exposures were evaluated using three non-consecutive 24-hour dietary recalls, measuring daily intake of various food groups and nutrients as defined by the Global Burden of Disease study. Depression outcomes were assessed at baseline (N=1039) and follow-up (N=551) using the Patient Health Questionnaire (PHQ-9, cut-off [&ge;]10). Logistic and Poisson regression analyses were performed, with results presented as odds ratios (OR) and relative risk ratios (RR), respectively. Four models were run: unadjusted, sociodemographic-adjusted, total energy (TE) intake-adjusted and fully adjusted (including sociodemographic information and TE intake). For longitudinal analyses of incident depression, baseline depression cases were additionally excluded (n=403). ResultsParticipants (average age 24.55 years) had a balanced distribution of sex (51.4% female) and race (48.6% Black), and a 29.45% baseline prevalence of depression. Higher milk intake was associated with a lower risk of incident depression (RR=0.94, 95% CI 0.91-0.98) in the TE-adjusted longitudinal model. Cross-sectionally, higher sugar-sweetened beverage consumption associated with higher odds of depression, while higher calcium intake (OR=0.48, 95% CI 0.31; 0.76) and vegetable consumption (OR=0.74, 95% CI 0.61, 0.91) were associated with lower odds of depression after TE intake adjustment. Higher fibre intake was associated with lower odds of depression in the unadjusted model. ConclusionHigher daily milk intake was associated with a lower risk of depression, while higher calcium, vegetable, and fibre intake were associated with a lower prevalence of depression in young adults. These findings suggest that prevention strategies for common mental disorders could include dietary approaches within mental health care.

BackgroundOptical coherence tomography (OCT) is increasingly used to investigate retinal structural changes across neurological and neuropsychiatric conditions. This systematic review and meta-analysis synthesises evidence examining retinal thickness in anxiety, depression, and substance use disorders (SUD) compared with healthy controls. MethodsA pre-registered systematic search (PROSPERO: CRD42024559542) of major databases following PRISMA guidelines was conducted. Case-control studies measuring retinal layer thickness via OCT in adults with DSM or ICD diagnosed anxiety, depression, or SUD were included. Multilevel random-effects models were used to calculate pooled standardised mean differences (SMD) and account for dependencies. ResultsThirty-three studies were included for narrative review, and 25 studies with 145 effect sizes were included for meta-analysis. The primary analysis, which pooled all disorders and effect sizes from available retinal thickness measures, found no significant differences between cases and controls (SMD = -0.20; 95% CI [-0.53, 0.14]; p = .244). Subgroup analyses for anxiety, depression, and SUD also yielded non-significant results (all p > .05). No specific retinal layer was consistently affected, and there was no evidence of an age x diagnosis interaction. Significant heterogeneity (Q = 756.57, p < .001) was present across analyses. ConclusionThis meta-analysis found no significant associations between retinal structural differences and anxiety, depression, or SUD. The field is characterised by high heterogeneity and publication bias, limiting the strength of evidence for the utility of OCT as a reliable biomarker for these conditions. Standardised, large-scale studies are needed with strict controls for confounding factors, including medication, disease stage and ocular parameters, alongside standardised OCT segmentation protocols. Article HighlightsO_LIFirst meta-analysis of OCT retinal thickness in anxiety, depression and SUD. C_LIO_LINo significant retinal thickness differences found between cases and healthy controls. C_LIO_LIAge and sex did not moderate the association between diagnosis and retinal thickness. C_LIO_LIHigh heterogeneity and publication bias limit utility of OCT as a neuropsychiatric biomarker. C_LIO_LIStandardised protocols are needed to clarify retinal changes in psychiatric research. C_LI

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.

ObjectivesElectroconvulsive Therapy (ECT) is an effective treatment for bipolar disorder, particularly in severe acute cases or for illness resistant to pharmacotherapy. However, the risk of relapse following ECT is high, necessitating intervention to reduce this risk. Based on findings from ECT studies in unipolar depression and its well-known mood-stabilizing properties, it is likely that lithium treatment may reduce the risk of relapse of bipolar disorder following ECT. Therefore, we conducted a target trial emulation using data from Danish nationwide registers to investigate whether lithium protects against relapse following ECT treatment of bipolar disorder. MethodsPatients discharged from their first psychiatric admission with a primary diagnosis of bipolar disorder between January 1, 2006, and June 1, 2024, who received at least six ECT treatments, were included. Follow-up began two weeks after discharge and continued until relapse, death, one year, or January 1, 2025. Patients were considered allocated to lithium treatment if they redeemed a prescription for lithium within the first two weeks after discharge from the index admission (ECT treatment). The outcome was time to relapse, defined by either psychiatric hospital admission or suicide. Cox proportional hazards regression, adjusted for potential confounders, was used to compare the outcome between patients allocated and not allocated to lithium treatment. ResultsAmong the 574 eligible patients (mean age 41.5 years, 61.3% women), 214 (37.3%) were allocated to lithium treatment and 360 (62.7%) were not allocated to lithium treatment. During follow-up, 56 patients (26.2%) in the lithium group and 135 patients (37.5%) in the non-lithium group experienced a relapse. Lithium treatment was associated with a substantially reduced risk of relapse (adjusted hazard rate ratio, 0.60, 95% CI=0.43-0.84). ConclusionLithium treatment after ECT may reduce the risk of relapse in patients with bipolar disorder. These findings should be followed up by a randomized controlled trial.