European Child & Adolescent Psychiatry

BackgroundOrganization, time management, and planning (OTMP) difficulties are associated with academic underachievement. OTMP skills training programs are effective in reducing OTMP deficits and improving academic performance. A randomized controlled trial of Homework, Organization, and Planning Skills (HOPS) for students ages 11-14 (1) found it to be effective with medium to large effects. In that study, HOPS was provided by counselors employed by the research team. This study is a replication examining HOPS under more authentic conditions when providers are employed by schools serving enrolled students. The primary aim is to evaluate HOPS offered by school providers in relation to treatment-as-usual/waitlist (TAU/WL). To respond to limited school resources post-COVID-19, HOPS is also provided by research team members, creating the opportunity to replicate the findings from the prior trial (1) and explore differential effectiveness when HOPS is implemented by school vs. research providers. MethodsStudents in about 30 schools serving students ages 11-14 will be enrolled. Schools are randomly assigned to HOPS vs. TAU/WL on a 2:1 ratio. Students assigned to HOPS schools are randomly assigned to a school vs. research provider on a 1:1 basis. Providers receive two hours of training and additional assistance on request. Child outcomes related to OTMP skills, homework, and academic performance are assessed at post-treatment, 6-month (from baseline) follow-up, and 12-month follow-up. HOPS sessions are video recorded for fidelity coding. Potential effect modifiers include student ADHD, oppositional defiant, and internalizing symptoms, and family socioeconomic level. Analyses will use mixed effects modeling. The goal of the study is to enroll 135 participants, yielding a minimal detectable effect size of 0.50, within the expected range based on prior research. DiscussionThe study is unique in examining intervention implementation and effectiveness when intervention is provided under authentic practice conditions. Trial RegistrationThis study was registered with clinicaltrials.gov (NCT04465708).

ObjectiveAlthough mental health and healthy lifestyle interventions are associated with functional outcomes in adolescence, the extent to which particular lifestyle factors explain relationships between mental health and outcome are unclear. Here we examined mediating effects of lifestyle factors on relationships between mental health and two functional outcomes measured 2-3 years later as well as the moderating effect of environmental risk factors on mediation strength in early adolescence. MethodsThis study analyzed data from 3 waves of the Adolescent Brain Cognitive Development Study (ages 10-11, 11-12, and 12-13). Mediating effects of sleep quality, screen time, physical activity and Mediterranean diet on the relationships between depression, anxiety, psychotic-like experience (PLE) distress, and total problems with two subsequent functional outcomes (academic functioning and social problems) were examined. Secondary analyses included environmental factors as moderators. ResultsSleep quality mediated 18.5%, 36.3%, 8.3%, and 3.4% of the relationships between depression, anxiety, PLE distress and total problems with academic functioning, respectively. Screen time was the second strongest mediating factor. For social problems, only sleep quality showed > 3% mediation (19.6% - 23.3%). Mediating effects of sleep and screen time on academic functioning decreased as financial adversity increased. Conversely, mediating effects of sleep quality on social problems increased with worsening family conflict, financial adversity, and school environment. ConclusionsThese results suggest that healthy lifestyle factors (in particular sleep quality) may partially explain the associations between mental health and functioning in adolescents and suggest that these effects are modulated by environmental factors. These results may have important implications for future intervention studies.

BackgroundParental genetics matters for childrens behavioural difficulties, but the extent to which this is due to direct genetic transmission versus environmentally mediated indirect genetic effects remains unclear. MethodsWe studied eight European birth cohorts with over 33,000 family-based trio samples. We analysed polygenic scores (PGSs) for 13 mental health and neurodevelopmental conditions and their composite indices (PC1 and mean) representing general neuropsychiatric liabilities, as well as educational attainment (EA) and alcohol and cigarette use, from children (PGSc), mothers (PGSm), and fathers. Child internalising, externalising, and total difficulties reported by mothers and/or fathers were examined at preschool and school ages. We then conducted multivariate meta-analyses to combine cohort-level results. FindingsWe observed several direct genetic effects on externalising difficulties, while indirect genetic influences were mainly identified for internalising difficulties. Specifically, child PGSs for attention-deficit/hyperactivity disorder (ADHD) and EA predicted higher and lower levels, respectively, of child externalising and total difficulties (all pFDR<0{middle dot}001; for school-aged externalising difficulties, PGSc-ADHD: {beta}=0{middle dot}121 [95% CI 0{middle dot}091 to 0{middle dot}151], pFDR<0{middle dot}0001; PGSc-EA: {beta}=-0{middle dot}095 [95% CI -0{middle dot}127 to -0{middle dot}063], pFDR<0{middle dot}0001), whereas maternal PGSs for major depressive disorder (MDD) and general neuropsychiatric liabilities were associated with internalising and total difficulties across parental raters and child ages (all pFDR<0{middle dot}05; for school-aged internalising difficulties, PGSm-MDD: {beta}=0{middle dot}049 [95% CI 0{middle dot}017 to 0{middle dot}081], pFDR=0{middle dot}016; PGSm-PC1: {beta}=0{middle dot}056 [95% CI 0{middle dot}022 to 0{middle dot}091], pFDR=0{middle dot}011). No statistically significant effects from paternal PGSs were identified. InterpretationIn this multi-cohort study, findings across multiple traits, raters, and ages supported several direct genetic effects of ADHD and EA on child externalising difficulties and indirect genetic effects on internalising difficulties, especially maternal depression and general neuropsychiatric liabilities. These suggest that child internalising difficulties are not solely driven by direct genetic transmission. More comprehensive research is needed to better understand the mechanisms involved, and ultimately how to ameliorate child behavioural difficulties. FundingEU, ERC, RCN, RCF, UKRI, SERI, DFG Research in contextO_ST_ABSEvidence before this studyC_ST_ABSIndirect genetic effects (IGEs) refer to the influence of parental genotypes on offspring outcomes beyond direct genetic effects (DGEs), for example via environmental pathways. While IGEs on offspring cognitive traits are well-established for educational attainment, evidence for IGEs of parental liabilities to mental health and neurodevelopmental conditions remains limited. To assess the current state of evidence, we conducted a systematic search of published studies applying trio-based polygenic score (PGS) designs to child and adolescent mental health outcomes. We identified 141 primary studies in MEDLINE, Embase, PsycInfo, and Web of Science, by 6 March 2025, after removing duplicates; following screening, 12 studies met inclusion criteria (see supplement for a full description including results). Ten out of the 12 studies focused on externalising outcomes, with little or inconsistent support for IGEs. When observed, IGEs were mainly driven by maternal liabilities to autism, educational attainment, and cognitive performance on child outcomes. The current evidence was too limited and heterogeneous to synthesize findings quantitatively, therefore a qualitative synthesis was conducted. Many studies were statistically underpowered, and the observed IGEs were in all cases sample-specific. There were no published multi-cohort studies. Added value of this studyWe integrated information across over 33,000 mother-father-child trios from eight European cohorts, investigating 18 PGSs from parents and children, using maternal and paternal ratings of offsprings internalising, externalising, and total difficulties as outcomes at both preschool and school age. We mainly observed DGEs on externalising difficulties, consistent with previous studies. Some evidence of IGEs was found for internalising and total difficulties. IGEs were often found to be maternally driven, with the most robust evidence across ages and raters emerging for maternal depression and general neuropsychiatric liabilities. Implications of all the available evidenceThe current evidence suggests that childrens behavioural difficulties, especially internalising difficulties, may be partly driven by the environment shaped by maternal neuropsychiatric liabilities. Ours and previous findings highlight a pressing need for more comprehensive studies across different cohorts, raters, outcomes, and time points to understand the true extent of IGEs in the intergenerational transmission of mental health.

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.

BackgroundThe present study examines the link between DNA methylation at the nerve growth factor-induced protein A (NGFI-A) binding domain of the NR3C1 1F promoter and later cognitive functions in children from families living in disadvantaged psychosocial conditions. MethodsParticipants were 132 children who took part in a Swiss Parents as Teachers (PAT) randomized controlled trial (72 in the intervention group, 60 in the control group). DNA methylation was quantified from saliva samples collected at age three using sodium bisulfite next-generation sequencing (NGS). Cognitive functions were assessed at age five using the SON-R 2.5-7 Intelligence Test. Results(a) DNA methylation at age three predicted lower IQ at age five through increased concentration problems; (b) participation in the three-year PAT program predicted lower methylation levels at the end of the intervention; and (c) early life stressors predicted lower IQ through increased methylation and concentration problems with descriptively stronger effects in the control group. ConclusionsThese findings demonstrate a link between early DNA methylation at the NGFI-A binding site of the NR3C1 1F promoter and later cognitive functions in children and highlight the role of early life stressors and the PAT intervention in shaping these associations.

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.

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.

Very preterm infants (<30 weeks gestation) are at elevated risk for neurodevelopmental and social-behavioral challenges. DNA methylation (DNAm) may provide a biological link between preterm birth and later behavioral outcomes. We examined associations between DNAm profiles at neonatal intensive care unit (NICU) discharge and at age 5 with Social Responsiveness Scale (SRS) scores which measure social communication, social interaction, and repetitive behaviors at age 5, including sex-specific effects, in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study. Epigenome-wide buccal DNAm was profiled at NICU discharge (n=218) and at 5 years (n=188). We identified 38 neonatal and 6 age-5 CpG sites associated with SRS scores (all q<0.05) using epigenome-wide association studies (EWAS) at each time point. Several CpGs mapped to genes involved in neurodevelopment including TCF4, KLC4, CAP2, PTDSS1, ADAM12, SENP1, CHN2, SH3D19, and ITGA1, with sex-specific effects observed for CpGs in CAMTA1 and GABBR1. Enriched pathways included neurodevelopment, cytoskeletal regulation, stress-response, and metabolic processes. DNAm patterns during early life, particularly the neonatal period, were associated with social-behavioral development in very preterm children. Findings in key genes such as TCF4 and CAMTA1 highlight potential epigenetic mechanisms linking early-life biology to later behavioral challenges.

ObjectiveThis study aimed to identify characteristics that define population need groups with similar mental health service needs within prisons and describe the mix of services required to meet those needs. MethodsMixed methods were used, including three iterative, semi-structured focus groups, followed by an online survey, seeking information on the characteristics that define service needs, how these can identify groups of people who require mental health care in prisons and the services required by each group. Participation was sought from prison health services, prison mental health services, non-government service partners and people with a lived experience. Focus group transcripts and free text survey responses were thematically analysed. Descriptive statistics were generated for online survey responses to Likert Scales to determine the levels of agreement with survey content. ResultsThe characteristics and service needs of four distinct population groups who require mental health care in prisons were defined: indicated prevention, mild, moderate, severe and complex. These groups were delineated using characteristics including presence of a diagnosed mental illness, level of functional impairment, presence of added complexity and service response required. The required service mix varied across need groups, however service types common across all groups included assessments, psychological therapies, peer support, lifestyle interventions and carer support. ConclusionsThe identified need groups and service descriptions will contribute to the evidence required for needs-based planning of mental health care in Australian prisons. This information can be used for planning a responsive, equitable, and needs-based mental health service system within custodial environments.

Background At present, there are no approved pharmacological treatments for people at clinical high risk for psychosis (CHR-P). We sought to assess the acceptability of cannabidiol (CBD): a promising candidate treatment for this population. Methods CHR-P individuals completed a survey which assessed their views on the acceptability of CBD, its expected effectiveness and side effects, and on formulation preferences. Results The sample comprised 55 CHR-P individuals (24.3 years and 69% female). Most (91%) were familiar with CBD, and had previously used cannabis (64%), and around half (42%) had tried over-the-counter CBD. 75% were willing to take CBD as an intervention for mental health problems. Most participants anticipated fewer side effects with CBD than with existing medications, and preferred tablet or capsule formulations over liquids. Discussion CBD is perceived as a highly acceptable treatment among CHR-P individuals.

Autism Spectrum Disorder (ASD) is a heterogenous condition that has no biologically relevant subtypes yet. Here, we utilized a multidimensional approach considering social deficits in ASD alongside negative valence and empathy dysfunction to distinguish ASD from Neurotypicals (NT) and to generate ASD subtypes using machine learning approaches. 114 subjects were analyzed, with 70 being NT and 44 ASD, all male with an IQ greater than 70, with 5 domains of personality (NEO-PI-r) and Reading the Mind the Eyes Test (RMET) scores included in the main classifier. We then used a multitude of behavioral (such as IQ, Broader Autism Phenotype, Autism Quotient, Interpersonal Reactivity Index) and clinical measures such as Autism Diagnostic Interview-Revised (ADI-R) alongside biological methods including DNA methylation of OXTR gene and resting-state functional connectivity (rsFC) to validate the putative subtypes. 30 ASD who received IN-OXT in a randomized, placebo-controlled, within-subject design and 17 new NT were part of the rs-FC analysis. A random forest tree algorithm was used to classify NT and ASD and Shapley Additive Explanation Values were used to describe the model and to cluster ASD subtypes using K-Means clustering. Three subtypes were generated with two of them being highly distinctive in behavioral and brain functional traits. One subtype named NASA (or Negative Affect and Social Aloofness) was characterized by high Neuroticism and Low warmth alongside lower rsFC between networks involved in social cognition, self-awareness, and sensory processing, such as Superior Temporal Sulcus and Sensorimotor Network; or ACC/Insula with visual cortex, Posterior Cingulate Cortex and visual cortex. The second subtype NADR (Neurocognitive and Affect Dysregulation with Resistance to Change) was characterized by higher DNA methylation of OXTR, hyperconnectivity between default mode network, reward areas and inferior frontal and fusiform networks. NADR has more cognitive difficulties and higher ADI-R scores as well as higher Neuroticism, higher personal distress, higher rigidity and lower openness. In a mixed model analysis, we found that IN-OXT in a dose dependent manner impacted NASA subtype by modulating rsFC between PCC and cerebellum and between Brainstem/Cerebellum and Parietal cortex to probably enhance social cognition and to reduce negative valence in this subtype.

Depression is a common and clinically significant mental health condition among university students, particularly those experiencing academic failure and course repetition, and is associated with adverse effects on cognitive functioning, emotional regulation, and academic performance. This study evaluated the efficacy of an internet-based cognitive behavioural therapy (iCBT) intervention, MoodGYM, in reducing depressive symptoms among repeating undergraduate students at the University of Zambia Ridgeway Campus. A quasi-experimental quantitative study design was employed. Seventy-five repeating undergraduate students with depressive symptoms were enrolled, with 33 assigned to the MoodGYM intervention group and 42 to a control group. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI) at baseline and after an eight-week intervention period. Statistical analyses included within-group and between-group comparisons, difference-in-differences estimation, and fixed-effects regression modelling. At baseline, participants exhibited predominantly moderate to severe depressive symptoms, with no statistically significant differences between the intervention and control groups. Following the eight-week intervention, the MoodGYM group demonstrated a statistically and clinically significant reduction in depressive symptoms, with median BDI scores decreasing from 22 to 16 (p < 0.001), representing a large effect size (Cohens d = 1.02). In contrast, the control group showed persistence or worsening of depressive symptoms over the same period. Difference-in-differences analysis confirmed a robust intervention effect, with an approximately 10-point greater reduction in depression scores among MoodGYM participants compared with controls (p < 0.001). These findings indicate that MoodGYM is an effective internet-based intervention for reducing depressive symptoms among repeating undergraduate students and offers a feasible and scalable approach to addressing student mental health needs in low-resource university settings.

BackgroundGlaucoma is identified as one of the leading causes of blindness worldwide. Its chronic nature and the potential for irreversible vision loss contribute to significant distress among affected individuals. Around 25% of individuals with glaucoma are estimated to experience depression, negatively impacting their quality of life and treatment adherence. However, data on the prevalence of depression among people with glaucoma in Tanzania is limited. This study aimed to determine the prevalence and factors associated with depressive symptoms among adults with glaucoma at Muhimbili National Hospital. Materials and methodsA cross-sectional study was conducted involving 297 adults with glaucoma, who were recruited consecutively from the ophthalmology clinic at Muhimbili National Hospital between July and November 2024. Data on biopsychosocial factors were collected using interviewer-administered questionnaires and medical records. Patient Health Questionnaire-9 and Oslo Social Support Scale assessed depressive symptoms and social support, respectively. Data were analyzed using STATA version 16. Logistic regression analyses identified factors associated with probable depression, with statistical significance set at p-value<0.05. ResultsThe mean age of participants was 63.6 years (SD{+/-}12.8), with 159 (53.5%) being female. Prevalence of probable depression was 11.1%, with 8.7% moderate, 2.4% moderately severe, and none reporting severe depressive symptoms. Having moderate social support (AOR 0.14; CI: 0.04-0.47; P=0.001) and strong social support (AOR 0.08; CI: 0.03-0.25; P<0.000) were significantly associated with lower odds of probable depression. ConclusionApproximately 1 in 10 individuals with glaucoma experience depression. Having good social support was identified as a protective factor against depression in people with glaucoma. These findings underscore the need for a multidisciplinary approach integrating psychosocial services into ophthalmology clinics.

Armed conflict in Sub-Saharan Africa has exposed millions of civilians to repeated and severe traumatic events, yet the prevalence of posttraumatic stress disorder (PTSD) and its associated determinants across the region have not been comprehensively synthesised. This study aimed to estimate the prevalence of PTSD and examine its associated factors among conflict-affected adult populations in Sub-Saharan Africa. Methodological quality was assessed using the Joanna Briggs Institute (JBI) criteria for cross-sectional and epidemiological studies A systematic search of PubMed, MEDLINE, Embase, Scopus, CINAHL, APA PsycINFO, the Cochrane Library, and the WHO Global Index Medicus (including African Index Medicus) was conducted for studies published between January 1, 2000, and May 31, 2025. Observational studies reporting PTSD prevalence among adults aged 18 years or older exposed to armed conflict were included. Study selection followed PRISMA 2020 guidelines, with independent screening by two reviewers. Random-effects meta-analyses with logit transformation were used to pool prevalence estimates, and determinants were synthesised narratively with emphasis on adjusted effect estimates. Heterogeneity was assessed using the I{superscript 2} statistic. Sixty-eight studies comprising 82,021 participants from 13 countries met inclusion criteria. The pooled prevalence of PTSD was 43% (95% CI, 35.9%-50.0%), with substantial heterogeneity (I{superscript 2} = 99.9%). Prevalence was highest among refugees (79%), followed by internally displaced persons (48%) and residents of conflict-affected communities (34%). Female sex was consistently associated with increased odds of PTSD (pooled adjusted odds ratio approximately 2.0), as were comorbid depression or depressive symptoms (AOR range 4.2-9.5). Additional correlates included cumulative trauma exposure, displacement, poor social support, and substance use. Overall, PTSD is highly prevalent among conflict-affected adults in Sub-Saharan Africa, underscoring the need for integrated, context-sensitive mental health strategies to address the enduring psychological consequences of armed conflict in the region.

Numerous studies have shown that adults with depression have distinct oculomotor alterations during saccade tasks, but whether similar alterations occur in adolescents is largely unknown. The purpose of this study was to test if eye-tracking during a structured saccade task could distinguish a group of adolescents with depression from healthy controls. We hypothesized that, due to overlapping circuitry between depression pathology and the oculomotor system, adolescents with depression would show alterations in fixation, saccade, and pupil behaviour. 51 adolescents with depression and 66 age-matched healthy controls completed the Interleaved Pro- and Anti-Saccade Task (IPAST) and several self-reported questionnaires for psychiatric symptoms. Oculomotor outcomes included fixation acquisition, fixation breaks, correct rate, saccadic reaction time, rate of correct express-latency pro-saccades, rate of express- and regular-latency anti-saccade errors, baseline pupil size, as well as pupil constriction and dilation sizes following task instruction. In comparison to healthy controls, adolescents with depression displayed impairments acquiring fixation (p<.001), made more fixation breaks in pro- (p=.023) and anti-saccade trials (p=.005), more anti-saccade errors (p=.013), more express-latency saccades overall (ps=.016), had a smaller pupil constriction in pro-saccade trials (p=.047) and had a smaller pupil dilation in pro- (p=.011) and anti-saccade trials (p=.041). No differences were found for saccadic reaction time, rate of correct pro-saccades, rate of regular-latency anti-saccade errors, pupil constriction size during anti-saccade trials, or baseline pupil size. Patients had psychiatric comorbidities and were using psychotropic medication. While this reflected clinical reality, these factors may have influenced oculomotor behaviour. Adolescents with depression had altered fixation, saccade, and pupil behaviour during IPAST. Given that many cases of adolescent depression remain undetected, accessible and objective screening approaches are highly needed. This oculomotor phenotype may be used in the development of such a screening tool to detect those at risk.

IntroductionResearch has shown that social and physical stressors of early-life adversity (ELA) can negatively affect long-term health trajectories. Despite differences in types of ELA exposure, previous studies have identified common health-related outcomes in adults who had experienced less favourable conditions during developmentally sensitive periods. This meta-analysis investigates the potential role of DNA methylation in mediating these adverse health trajectories by identifying common biological signatures across cohorts with distinct adversity exposures and environmental backgrounds. Materials and MethodsDNA methylation data from previously published studies was used to perform a meta-analysis on 227 individuals across three cohorts. These include the EpiPath cohort consisting of adults who were exposed early institutional care, ImmunoTwin cohort consisting of adversity discordant monozygotic twin pairs and lastly a cohort of young children exposed to early institutional care. ResultsDNA methylation analysis across the three cohorts revealed differential methylation at CpG loci associated with 15 genes common to all cohorts. These genes are involved in neuronal development, chromatin remodeling and metabolism. Pathway enrichment analysis of the combined dataset showed potential associations with oxytocin signalling, regulation of nervous system development, and calcium signalling in relation to the later-life phenotype of the adversity exposed individuals. In addition, a poly-epigenetic score was developed by identifying a subset of 200 differentially methylated CpG sites through PLS-DA analysis with the combined beta matrix of these cohorts. ConclusionThis study highlights the long-term impact of adversity by identifying common DNA methylation signatures of negative life experiences across three cohorts. The development of a poly-epigenetic score represents the first steps towards identifying group differences by combining weighted methylation values for CpG sites of interest. This method illustrates the potential to track changes in individuals across long-term studies that may benefit research in lifelong healthoutcomes.

Rare pathogenic variants in many genes contribute to neurodevelopmental disorders (NDDs), including intellectual disability and/or global developmental delay (ID), autism spectrum disorder (ASD), epilepsy (EP), and cerebral palsy (CP). These conditions frequently co-occur and share genetic etiologies, yet the broader phenotypic eYects and the extent of shared versus distinct genetic influences remain unclear. Here, we adopt a cross-disorder framework to examine NDD genes across four diagnostic categories, characterize gene-associated phenotypic profiles, and identify convergent pathways that help refine how pathogenic variants in these genes shapes clinical outcomes. Using a discovery cohort of 8,973 probands with disease-causing variants in 263 NDD genes, we performed phenotype-based gene clustering and identified six distinct gene clusters. These clusters reveal structured patterns of genetic overlap, showing that subsets of NDD genes preferentially contribute to specific disorder combinations of ID, ASD, EP, and CP. The largest gene cluster was characterized by ID, whereas the other five included one enriched for ASD and ID, two for EP and ID and two for CP and ID, each with significantly diYering frequencies. In an independent validation cohort of 19,704 probands, five of the six clusters were replicated. Gene Ontology enrichment analyses revealed distinct biological processes in each cluster, suggesting that coherent molecular mechanisms underlie the diYering NDD diagnostic profiles. Together these findings demonstrate that NDD genes fall into coherent clusters that consistently map onto characteristic phenotype profiles, providing a framework to inform future therapeutic strategies and support early prognostication for individuals with pathogenic variants in NDD genes.

Actigraphy is a popular behavioral sleep assessment tool in research and clinical practice. Hierarchical hand-scoring approaches remain the standard for actigraphy rest interval estimation, but can be impractical for large cohort studies and suffer from reproducibility problems. We developed a semi-automated pipeline (actiSleep) to set rest intervals consistent with best-practice hand-scoring algorithms incorporating event marker, diary, light, and activity data. To evaluate actiSleep performance, we used data from an observational study of 51 adolescents (14-19yr), with and without family history of bipolar disorder. Participants completed 2 weeks of wrist actigraphy and daily sleep diary. We first hand-scored records using a standardized hierarchical algorithm incorporating event marker, diary, light, and activity data. We then compared the hand-scored rest intervals to those from actiSleep and two automated activity-based algorithms (Activity-Merged, Activity-Only). Activity-Only used activity-based sleep estimation and Activity-Merged joined closely adjacent rest intervals. For rest onset, rest offset, and rest duration, all algorithms had strong mean agreement with hand-scoring: actiSleep estimates were within 1-3 minutes, Activity-Merged within 2-4 minutes, and Activity-Only within 7-14 minutes. However, actiSleep had notably better (narrower) margins of agreement with hand-scoring, as evidenced by Bland-Altman plots, and greater positive predictive value and true positive rates for rest detection, especially in the 60 minutes surrounding the onset and offset of the rest interval. The actiSleep algorithm successfully estimates actigraphy rest intervals comparable to hand-scoring while avoiding pitfalls of activity-only algorithms. actiSleep has potential to replace hand-scoring for research in adolescents but requires further testing and validation in other samples.

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.

Objective: Posttraumatic stress disorder (PTSD) after a traumatic birth is a serious but overlooked maternal morbidity, affecting ~20% of women following medically complicated deliveries. PTSD can undermine maternal caregiving. Rapid screening tools suited to busy obstetric settings are lacking. We developed and evaluated a brief screener, derived from the 20-item PTSD Checklist for DSM-5 (PCL-5), to identify PTSD related to childbirth. Study Design: We enrolled 107 women with traumatic childbirth. Participants completed the PCL-5 and the gold-standard clinician diagnostic interview for PTSD (CAPS-5); depression was measured with the Edinburgh Postnatal Depression Scale (EPDS). Bootstrap resampling with LASSO regression identified PCL-5 items most associated with PTSD. Firth logistic regression models estimated diagnostic accuracy. Sensitivity, specificity, area under the ROC curve (AUC), and Youden's J statistic determined performance and optimal cut-off. Results: A six-item version of the PCL-5 (PCL-5 R6), statistically derived from the full scale, showed excellent discrimination for PTSD compared with clinician evaluation (AUC = 0.95; 95% CI, 0.89-1.00). A cut-off score of 7 yielded high sensitivity (0.96) and good specificity (0.83), with an overall diagnostic efficiency of 0.86, detecting most PTSD cases while minimizing false positives. The PCL-5 R6 correlated moderately with the EPDS (rho = 0.53), showing that a depression screen alone cannot reliably detect PTSD. Conclusions: A short, 6-item PCL-5 provides a valid, efficient tool for detecting childbirth PTSD. Its brevity and accuracy make it practical for integration into routine postpartum care, enabling timely mental health screening.