Down Syndrome Regression Disorder (DSRD) is an acute neurocognitive regression in individuals with Down syndrome (DS), causing a profound loss of acquired skills. DSRD increases demands on caregivers, to sleep disturbances, financial distress, and negative impacts on caregiver-reported social connections and perceived social support. The goal of this study was to characterize the caregiver-reported impacts of DSRD on social relationships by comparing their experiences to those of caregivers of individuals with DS and other neurological disorders (DSN).

This is a narrative burden-of-care study, not a network study. Using cross-sectional study design, caregivers of individuals with DSRD (n = 228) and DSN (n = 137) were recruited from a neurology clinic and a DSRD Facebook support group. Participants completed the DSRD Caregiver Distress Survey (CDS), which included four qualitative, open-ended questions focused on self-perception of adult friendships, social relationship impact, spouse/partner impact, and perceived shrinkage of social world. Responses were analyzed using thematic coding; resulting theme frequencies summarize caregiver-reported perceptions and narratives and do not represent objectively measured social network structure.

In the DSRD cohort, a high-level overview revealed that 65.66% of responses reported a negative impact on adult friendships, while 71.21% reported a negative impact on social relationships. A negative impact on spouse/partner relationships was reported in 51.53% of responses, and a perceived shrinkage of social world was found in 52.82%. Caregivers in the DSRD group were significantly more likely to report "Social Withdrawal and Isolation" (43.2% vs. 17.9%, p = 0.006), "Loss of Community Participation and/or Support" (16.7% vs 4.5%, p = 0.043) and a "Perceived Enduring Loss of Social Connections" (35.3% vs. 8.7%, p = 0.002) compared to the DSN group.

This study's findings reveal a significant and complex process of perceived social disengagement among caregivers describing social withdrawal and loss of social connections that they experienced as enduring. The results emphasize the need for early interventions that address the individual's needs but also address the caregiver's social and mental health to prevent perceived long-term social isolation.

Background and PurposeThis qualitative study is part of a larger Indigenous community-led project in Southern Ontario, Canada, to support Indigenous fathers and Two-Spirit parents through the development of a culturally relevant parenting program. Conducted during Phase 2, this study pretested six well-established instruments to assess their clarity, comprehension, and cultural safety for use in evaluating the parenting program in Phase 3.Methods and ProceduresSix participants, all of whom were First Nations or Métis, either expecting a baby or parenting a child under the age of three, completed five instruments, specifically the Parenting Sense of Competence Scale (PSOC), Edinburgh Postnatal Depression Scale (EPDS), Relationship Assessment Scale (RAS), General Self-Efficacy Scale (GSES), and either the Paternal Antenatal Attachment Scale (PAAS) or Paternal Postnatal Attachment Scale (PPAS). Semi-structured interviews were conducted to gather insights on the instruments' instructions, terminology, response scales, and cultural relevance. Data were analyzed using conventional content analysis.ResultsParticipants identified barriers to understanding and accurately completing the instruments, including challenging terminology, ambiguous response scales, and cultural safety concerns. Recommendations included simplifying language, clarifying scale anchors, adding culturally relevant questions, and establishing culturally safe support pathways for participants disclosing distress.ConclusionEuro-Western developed instruments require refinement to ensure accessibility, cultural relevance, and safety for Indigenous fathers and Two-Spirit parents. This includes adapting tools to reflect Indigenous literacy frameworks and holistic wellness perspectives. This study underscores the ethical imperative for researchers to ensure cultural appropriateness and safety when engaging Indigenous communities in research.

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by difficulties in communication, deficits in social interaction, and repetitive behavioral patterns. Global prevalence estimates range from 1% to 2%, with variations attributed to cultural, social, and methodological factors. In Africa, research remains limited and highly heterogeneous, largely due to scarce diagnostic resources, persistent stigma, and the absence of consistent public policies.

A systematic search was conducted across PubMed, Embase, Scopus, and PsycInfo for articles published up to May 2025. Cross-sectional studies conducted in school-based or community populations were included. The analysis followed PRISMA guidelines, and the protocol was registered with PROSPERO (CRD420251138668). A random-effects model using the Freeman-Tukey transformation for variance stabilization was employed for statistical synthesis.

Seven studies from Egypt, Kenya, Uganda, and Nigeria, comprising 71,341 participants, were included. Across included studies, reported ASD prevalence ranged from 0.54% to 23.8%. When pooled and stratified by methodological criteria, clinically confirmed ASD prevalence was 1% (95% CI, 0.0-1.0%), whereas high-risk screening prevalence was 4% (95% CI, 0.0-16.0%), with very high between-study heterogeneity (I² = 99.8%).

Despite substantial methodological heterogeneity, ASD prevalence estimates in Africa appear comparable to those reported in high-income countries. The marked disparity between high-risk screening prevalence and confirmed diagnoses highlights the urgent need to expand diagnostic confirmation services and strengthen training for primary healthcare professionals to bridge the gap between risk identification and definitive diagnosis across the continent.

Adults with myotonic dystrophy type 1 who require non-invasive ventilation (NIV) often have difficulty with adherence. Few risk factors for non-adherence have been identified, and these are mostly unmodifiable. As part of a quality assurance initiative, we sought to identify psychosocial barriers to NIV adherence to improve supports around isolation and mental health. We found that substance use was associated with non-adherence to NIV in our cohort. Cognitive impairment, the receipt of provincial income support, presence of a psychiatric condition, living alone, and marital status were not associated with NIV adherence. Interventions that limit the impact of substance use may improve NIV in this population.

Adverse childhood experiences (ACEs) are associated with persistent mental health risks and brain structural differences across adulthood, yet their long-term neurobiological relevance in aging populations remains unclear. Given that ACEs are common and societies are aging, understanding how early adversity relates to mental and brain health across the lifespan is an important goal. This preregistered study examined whether ACEs are associated with mental health symptoms in mid- to late adulthood, and whether regional brain structure may account for part of this relationship. Cross-sectional data of the Hamburg City Health Study were used, involving participants aged 46-78 years with available magnetic resonance imaging data (N_total = 2 624; eligible: n_{analysis sample} = 1 900). Mental health status was quantified using the Patient Health Questionnaire-9 and the General Anxiety Disorder-7 questionnaire, while ACEs were assessed using the 10-item ACE-questionnaire. Predefined regions of interest (ROI) were the hippocampus, amygdala, and dorsolateral prefrontal cortex. Bayesian statistical analysis provided strong evidence for an association between ACEs and both mental health outcomes but did not confirm the hypothesized mediation by ROI-level brain morphology. Exploratory whole-brain voxel-based morphometry revealed significant regional grey matter volume (rGMV) reductions in individuals with 3 or more ACEs, affecting bilateral limbic and frontal regions-including the nucleus accumbens, gyrus rectus, and insula. These reductions were more pronounced and widespread in individuals with 4 or more ACEs, extending to areas in the dorsolateral and medial prefrontal cortex, anterior cingulate cortex, inferior parietal and temporal gyri, occipital cortex, and cerebellum. Notably, no increases in rGMV were observed for any ACE group. This suggests a dose-dependent effect, with 4 or more ACEs marking a potential threshold for more distributed neuroanatomical alterations. These results derived from a representative general population study extend the understanding of the possible effects of ACEs by providing evidence that structural changes associated with ACEs could last into mid and late adulthood similarly to mental health outcomes.

Veterans involved in the criminal legal system (CLS) exhibit disproportionately high rates of comorbid mental health and substance use disorders (COD) and homelessness-conditions that increase both the risk of recidivism and suicide. Despite elevated risk, limited research has examined the relationship between criminogenic risk factors and suicidality in this population.

This study examined differences in criminogenic risk, psychiatric burden, and social determinants of health (SDOH) among CLS-involved veterans with COD, comparing those with suicidality risk to those without.

Baseline data were analyzed from 127 veterans admitted to three Department of Veterans Affairs (VA) Mental Health Residential Rehabilitation Treatment Programs who were enrolled in a randomized controlled trial of the MISSION-CJ intervention (ClinicalTrials.gov Identifier: NCT04523337). Eligible veterans had recent CLS involvement and documented COD diagnoses. Assessments included the Level of Service Inventory-Revised (LSI-R), the Measures of Criminal Attitudes and Associates (MCAA), structured psychiatric interviews, standardized symptom inventories, and measures of social determinants of health. Suicidality risk was defined as experiencing recent thoughts of suicide and/or attempted suicide in their lifetime.

Most veterans (80%) were classified as having moderate-high to high criminogenic risk based on total LSI-R scores. Compared to those without suicidality risk, veterans with suicidality risk demonstrated significantly higher criminogenic risk as evidenced by total LSI-R scores (p = .01), more antisocial attitudes (p = .04), particularly entitlement and violence beliefs (p = .02, p = .01, respectively), greater emotional and functional impairment (p < .001), and a higher prevalence of probable posttraumatic stress disorder (PTSD; 64% vs. 41%, p = .009). SDOH, including unstable housing and limited community integration, were highly prevalent but did not significantly differ between those with and without risk of suicide.

Among CLS-involved homeless veterans with COD, suicidality was associated with elevated criminogenic risk and greater psychiatric burden, particularly PTSD. These findings underscore the need for integrated interventions that address both criminogenic and behavioral health factors to support recovery, reduce suicide risk and mental health symptoms, and mitigate CLS recidivism.

This study was preregistered at https://ClinicalTrials.gov with registration number NCT04523337.

Migrants living in socioeconomically disadvantaged neighborhoods in Sweden were overrepresented among the infected and deceased in coronavirus disease 2019 (COVID-19) and vaccination coverage was substantially lower, despite being free of charge. The overarching aim of this study was to analyze the experiences of operating a multilingual telephone service for public health crisis communication targeting migrant communities in Sweden during COVID-19. A secondary objectives was to identify specific opportunities and challenges in delivering culturally appropriate health information during a pandemic crisis.

A qualitative design based on in-depth interviews with 12 health communicators staffing the telephone service was used. Additional quantitative descriptive data on the use of the telephone service are provided for context.

The quantitative data revealed that relatively few callers requested basic information about the virus or asked about topics such as where to turn in case of illness. The most common topic was testing for current infection. The thematic analysis identified seven major themes: The rationale behind a multilingual telephone service; the convergence of language, culture, and professional competence in trust building; dialogical dissemination of knowledge; cooperation with other actors and organizations; responding to misinformation and myths; managing emotions, existential concerns, and mental distress; and lessons for future health crisis response.

For dissemination of information about COVID-19 and vaccination to migrants during the pandemic, experiences from the multilingual telephone service point to the value of communication that includes the possibility of dialogue with health professionals in a culturally safe mode using one's native language. For future health crises, our findings emphasize the importance of having a communication strategy targeting vulnerable groups in place as a part of a comprehensive pandemic plan when the need emerges.

The study protocol has been preregistered on the Open Science Framework (osf.io/rt47j).

Relatives' expressed emotions (EE) and caregiving appraisals are associated with the prognosis of individuals with psychotic disorders as well as relatives' own well-being. The main aim of the present study was to examine whether sociodemographic factors, patients' clinical characteristics, relatives' health and quality of life (QoL), and relatives' perceived support explained a significant amount of the variance in expressed emotion (EE) and caregiving appraisals among relatives of patients with psychotic disorders.

Baseline data from The Implementation of guidelines on Family Involvement for persons with Psychotic disorders (IFIP) trial were compiled from 231 patient-relative pairs across 15 Community Mental Health Centres (CMHC). Relatives completed assessments on EE; emotional overinvolvement (EOI) and critical comments (CC) (Family Questionnaire), negative and positive caregiving appraisals (Experience of Caregiving Inventory), health and QoL (Care Related Quality of Life), healthcare professional support (Caregiver Well-being and Support) and sociodemographic factors. Patients reported on their own difficulties with mental health and functioning (Behavior and Symptom Identification scale) while clinicians assessed patients' functioning (Global Assessment of Functioning) and sociodemographic factors. Pearson and Spearman correlations and hierarchical multiple linear regressions were used for statistical analyses.

Duration since first psychosis diagnosis, patients' mental health and functioning, and relatives' health problems explained a substantial proportion of variance in relatives' EOI and negative caregiving appraisals. Together with household income level, duration since first psychosis diagnosis explained a significant amount of the variance in positive caregiving appraisals. Relatives' perceived support from healthcare professionals explained a significant amount of the variance in CC and negative caregiving appraisals, even after adjusting for contextual variables.

Psychotic disorders entail significant burdens and shape the family climate for both patients and their relatives. Negative caregiving appraisals and EOI may reflect normal reactions to the responsibilities and challenges relatives face. EOI and CC, however, may be associated with distinct factors, necessitating tailored psychoeducational and support interventions. The findings suggest that relatives' perceived support from healthcare professionals could have a substantial positive impact on CC and negative caregiving appraisals, which is important for clinicians to recognise and address.

Despite the crucial distinction between insomnia symptoms and a diagnosed disorder, population-level studies based on contemporary criteria and clinical interviews are scarce. This study therefore examined the insomnia spectrum by assessing the prevalence, identifying subtypes, and exploring associations with sociodemographic factors and comorbid mental disorders for both conditions.

This large-scale, community-based cross-sectional study was conducted in Beijing from October to December 2021. A sample of 10,778 adults was recruited via multistage stratified random sampling. Trained psychiatrists conducted standardized diagnostic interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) to collect data on insomnia disorder and mental disorders. Descriptive analysis and weighted Rao-Scott chi-square tests, were performed using the Statistical Analysis System (SAS, version 9.4).

The weighted prevalence rates were 17.7% for subjective sleep problems, 10.7% for clinically assessed insomnia symptoms, and 3.0% for DSM-5-diagnosed insomnia disorder. Among insomnia subtypes, initial insomnia was most prevalent, both as a symptom (8.1%) and a disorder (2.6%). Furthermore, insomnia disorder prevalence varied by sociodemographics, being higher in females, older adults (≥ 60 years), and those with lower education. Among individuals with insomnia disorder, 31.3% had comorbid other mental disorders, particularly alcohol-related disorders (13.4%). Conversely, insomnia disorder was observed in 14.4% of individuals with other mental disorders, with the highest prevalence in depressive (21.4%) and anxiety disorders (19.2%).

The marked disparity between prevalent insomnia symptoms and formal diagnoses, compounded by significant psychiatric comorbidity, mandates a public health shift toward population-level screening and early intervention. This imperative includes adopting standardized diagnostics and implementing integrated, transdiagnostic treatment models as a pivotal preventive strategy.

Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality and there are limited therapies¹. Although endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR transducer ATF6α remains unclear². Here we demonstrate the function of ATF6α as an ER-stress-inducing tumour driver and metabolic master regulator restricting cancer immunosurveillance for HCC, in contrast to its well-characterized role as an adaptive response to ER stress³. ATF6α activation in human HCC is significantly correlated with an aggressive tumour phenotype, characterized by reduced patient survival, enhanced tumour progression and local immunosuppression. Hepatocyte-specific ATF6α activation in mice induced progressive hepatitis with ER stress, immunosuppression and hepatocyte proliferation. Concomitantly, activated ATF6α increased glycolysis and directly repressed the gluconeogenic enzyme FBP1 by binding to gene regulatory elements. Restoring FBP1 expression limited ATF6α-activation-related pathologies. Prolonged ATF6α activation in hepatocytes triggered hepatocarcinogenesis, intratumoural T cell infiltration and nutrient-deprived immune exhaustion. Immune checkpoint blockade (ICB)⁴ restored immunosurveillance and reduced HCC. Consistently, patients with HCC who achieved a complete response to immunotherapy displayed significantly increased ATF6α activation compared with those with a weaker response. Targeting Atf6 through germline ablation, hepatocyte-specific ablation or therapeutic hepatocyte delivery of antisense oligonucleotides dampened HCC in preclinical liver cancer models. Thus, prolonged ATF6α activation drives ER stress, leading to glycolysis-dependent immunosuppression in liver cancer and sensitizing to ICB. Our findings suggest that persistently activated ATF6α is a tumour driver, a potential stratification marker for ICB response and a therapeutic target for HCC.