BACKGROUND: Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance. METHODS: We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals (aged 7-90 years, 54% female), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 noncarriers. CNV penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk of developing either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder, and congenital malformations). RESULTS: For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus. CONCLUSIONS: Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.

OBJECTIVE:To compare the prevalence of psychiatric conditions in a population-based cohort of people with intellectual disability and matched comparators in New South Wales, Australia. METHOD:The study cohort included 97,644 people with intellectual disability and 451,502 comparators aged ⩾ 5 between 1 July 2001 to 30 June 2018. We used linked records of hospital admissions, emergency department presentations, ambulatory mental health service contacts, and Medicare rebates to identify any, serious, and specific psychiatric conditions. RESULTS:People with intellectual disability showed greatly elevated period prevalence of any psychiatric condition (76.0% vs 38.3%), serious mental illness (16.2% vs 5.1%), and all specific psychiatric conditions compared to comparators. Among people with intellectual disability and congenital/developmental conditions, people with Down syndrome showed reduced risk of most psychiatric conditions while people with attention-deficit hyperactivity disorder and people with learning disorders showed increased risk. Age-specific analysis showed earlier onset of dementia and heightened prevalence of self-injury/suicidality in adulthood among people with intellectual disability. Annualised prevalence trends showed increases in 2006-2007 for most psychiatric conditions and decreases in 2014-2015 to 2017-2018. CONCLUSIONS:The higher prevalence of psychiatric conditions in people with intellectual disability indicates the importance of systemic responses to address the mental health needs of this population. Our findings highlight the importance of considering the psychiatric profiles of specific congenital/developmental conditions among people with intellectual disability, and the need to provide targeted services to high-risk groups such as those with co-occurring attention-deficit hyperactivity disorder.

The initiation of cognitive impairment is triggered by a myriad of pathological events occurring decades before clinical symptoms manifest. Perturbed glucose and fatty acid metabolism notably contribute to the development of cognitive impairment, progressing further into clinical dementia. These metabolic alterations are evident in plasma through changes in specific metabolites. Notably, these changes are characteristic features in the pathophysiology of depression, a significant risk factor for cognitive impairment. This project aims to establish a blood-based biomarker signature for early identification of cognitive changes in individuals with depression. Moreover, it aims to assist in diagnosing and understanding disease progression by quantifying plasma metabolite levels linked to fatty acid metabolism in samples obtained from participants in the Sydney Memory and Ageing Study. Plasma samples underwent analysis to quantify fatty acids and carnitines using chemical derivatization through UPLC-MRM/MS coupled with a 4000 QTRAP mass spectrometer which was equipped with an electrospray ion (ESI) source and operated in the multiple-reaction monitoring (MRM) mode with negative-ion (-) detection.10-μL aliquots of each of the resultant calibration solutions and each of the sample solutions were injected for analysis. ANCOVA, revealed significant changes in the levels of several biomarkers including glycolic acid (p-value: 0.033), C181 carnitine (p-value: 0.013), glutaric acid (p-value: 0.08) levels in groups with Mild Cognitive Impairment (MCI) and MCI with comorbid depression compared to healthy groups. ROC curve analysis demonstrated that glutaric acid effectively distinguished between MCI and non-MCI participants. The optimal threshold for classifying participants into MCI and non-MCI groups was determined using the Youden Index to dichotomize them based on high and low biomarker levels. Logistic regression analysis, adjusting for age, sex, APOE ε4 genotype, and comorbid depression, revealed a significant association between glutaric acid levels and cognitive impairment in the context of depression, with a p-value of <0.001 and an odds ratio of 2.49. Glutaric acid proved to be a reliable discriminator between participants with MCI and those without MCI. The aforementioned findings revealed a strong correlation between glutaric acid and cognitive impairment associated with depression which could be used as biomarker for early detection of cognitice impairment.

Apathy (loss of motivation or goal-directed behaviour) and depression each confer risk for dementia, cardiovascular disease and mortality in older adults. Mechanisms for this are not yet understood, and may involve systemic inflammation. However, this has received little attention, particularly in older adults where depression may present differently. Symptoms of apathy, fatigue, and physical symptoms are more common in late-life depression. This research aims to investigate whether apathy, depression and fatigue are differentially associated with inflammatory biomarkers in older adults. 1,037 community-dwelling older adults without dementia (aged 70-90, 55% women) completed self-report assessments including measures of apathy and depression from the Geriatric Depression Scale, and fatigue from Assessment of Quality of Life-6D. Inflammatory biomarkers from early morning fasting blood collection included C-reactive protein (CRP) and interleukin-6. Logistic regressions examined associations between levels of biomarkers and apathy, depression and fatigue separately. Analyses were initially unadjusted, then adjusted for baseline age, sex, education, global cognition (MMSE), health conditions, medications and BMI. Interleukin-6 was associated with apathy, depression and fatigue in unadjusted models (odds ratio [OR] per natural log unit increase in IL-6: 1.73, 95% confidence interval [CI] 1.38-2.22; OR 1.56, 95% CI 1.12-2.15; OR 1.72, 95% CI 1.14-2.59 respectively). The association with apathy remained significant after adjustment for other symptoms, socio-demographics, cognition and health-related covariates, but findings for depression and fatigue were attenuated. CRP was associated with apathy and fatigue (OR 1.10, 95% CI 1.00-1.21; OR 1.34, 95% CI 1.11-1.60 respectively) although the former was attenuated by adjustment for covariates. Previous associations between CRP and depression were not replicated. In older persons, apathy and fatigue were differentially linked with inflammatory biomarkers, whereas previous associations between inflammation and depression were not replicated. Findings confirm the importance of fatigue, and provide novel insight into apathy, as prevalent and impairing symptoms which map to peripheral inflammation in older adults. Inflammation may at least partially underly the complex associations between apathy, depression and poorer health outcomes including dementia.

Genome-wide association studies (GWAS) have been successful in identifying genetic variation associated with a wide range of phenotypes. However, more detailed knowledge of their functional significance is required to provide insights into the molecular mechanisms involved. Single Nucleotide Polymorphisms (SNPs) that influence gene expression (Expression Quantitative Trait Loci-eQTLs) may be one such functional mechanism. As gene expression may change over the lifespan, it is important to identify eQTLs for specific age groups. In this study, we aimed to identify blood eQTLs in older adults. Peripheral blood was collected from participants of the Sydney Memory and Ageing Study (Sydney MAS, N = 445, mean age +/- SD = 83.38 +/- 4.31) and RNA extracted. Gene expression and SNP genotyping were assessed using arrays. Genome-wide eQTL analyses were undertaken using linear mixed-models. Replication was undertaken in the Older Australian Twins Study (OATS, N = 283, mean age = 75.86 +/- 5.28). In the discovery cohort (Sydney MAS), a total of 10,468 unique eQTLs were identified influencing the expression of 1402 probes (1229 genes). A total of 6554 eQTLs were replicated in OATS, out of the 7339 that were available for analysis. We have identified, replicated, and described a catalogue of blood eQTLs in older adults. Noting that replication of these results in independent samples of older adults is required given our modest sample size. However, this information will be a useful resource for further studies, particularly in assessing the potential functions of SNPs identified in GWAS focussing on age-related traits.

Background Understanding whether apathy in older adults is related to incident dementia and mortality could help identify at-risk individuals, and inform public health efforts. This study aimed to investigate associations between apathy and these outcomes over long-term follow-up, and their independence from the overlapping symptoms of depression and fatigue. Methods In an Australian population-based cohort of 1,030 community-dwelling older adults aged 70-90, without dementia at baseline, apathy was assessed using the self-report Geriatric Depression Scale-3A subscale. Incident dementia was established via consensus diagnosis over 12 year follow-up, and mortality by record linkage over 18 years. We calculated hazard ratios (HRs) using Cox proportional hazards analyses. We repeated analyses adjusting for depression, fatigue and covariates, accounting for competing risk of mortality, and excluding short-term cases. Findings Unadjusted primary analyses showed the presence of self-reported apathy was associated with higher risk of dementia (HR 1.45, 95% confidence interval (CI) 1.05-2.00) and mortality (HR 1.76, 95% CI 1.43-2.16). Participants with apathy developed dementia a year earlier, and died three years earlier. These findings remained significant when adjusting for depression. The association with dementia was no longer significant when adjusting for fatigue or covariates, nor when taking mortality into account or excluding those cases where dementia developed in the shorter term. Interpretation The presence of apathy may represent an important risk indicator for dementia and mortality in older adults without dementia, independent of depression. Its association with dementia may reflect reverse causality. Future studies are needed to better understand the causal relationships that may underpin this observed association in the short and long-term, and the utility of apathy for screening in public health settings. ### Competing Interest Statement H.B. is or has been an advisory board member or consultant to Biogen, Eisai, Eli Lilly, Medicines Australia, Roche, and Skin2Neuron. P.S.S. was a member of the Expert Advisory Committees for Biogen and Roche Australia in 2020-22, unrelated to the current work. He is supported by an NHMRC Investigator Grant. J.R. has received honorarium from Merck Sharp & Dohme (MSD) for giving educational talks to health professionals. All other authors declare they have no competing interests. ### Funding Statement This doctoral research was supported by co-funding from Dementia Australia Research Foundation-Dementia Collaborative Research Centres Half-Funded PhD Scholarship and the Centre for Healthy Brain Ageing (CHeBA), and top-up scholarships from CHeBA Josh Woolfson Memorial Scholarship and Kwan Fung and Yuet Ying Fung Healthy Brain Ageing Research Award Fund and Brain Sciences UNSW Collaborative PhD Grant-In-Aid. The Sydney Memory and Ageing Study has been funded by three National Health & Medical Research Council (NHMRC) Program Grants (ID No. ID350833, ID568969, and APP1093083). DNA samples were extracted by Genetic Repositories Australia, an Enabling Facility, which was supported by an NHMRC Grant (ID No. 401184). Blood samples were collected by South-Eastern Area Laboratory Service (SEALS). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of the University of New South Wales and South-Eastern Sydney and Illawarra Health Service gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes De-identified individual participant data collected during the Sydney Memory and Ageing Study are available to researchers who provide a methodologically sound proposal. Proposals should be directed to the Centre for Healthy Brain Ageing; to gain access, data requestors will need to sign a data access agreement.

Alzheimer's disease (AD) brain markers are needed to select people with early-stage AD for clinical trials and as quantitative endpoint measures in trials. Using 10 clinical cohorts (N = 9140) and the community volunteer UK Biobank (N = 37,664) we performed region of interest (ROI) and vertex-wise analyses of grey-matter structure (thickness, surface area and volume). We identified 94 trait-ROI significant associations, and 307 distinct cluster of vertex-associations, which partly overlap the ROI associations. For AD versus controls, smaller hippocampus, amygdala and of the medial temporal lobe (fusiform and parahippocampal gyri) was confirmed and the vertex-wise results provided unprecedented localisation of some of the associated region. We replicated AD associated differences in several subcortical (putamen, accumbens) and cortical regions (inferior parietal, postcentral, middle temporal, transverse temporal, inferior temporal, paracentral, superior frontal). These grey-matter regions and their relative effect sizes can help refine our understanding of the brain regions that may drive or precede the widespread brain atrophy observed in AD. An AD grey-matter score evaluated in independent cohorts was significantly associated with cognition, MCI status, AD conversion (progression from cognitively normal or MCI to AD), genetic risk, and tau concentration in individuals with none or mild cognitive impairments (AUC in 0.54-0.70, p-value < 5e-4). In addition, some of the grey-matter regions associated with cognitive impairment, progression to AD ('conversion'), and cognition/functional scores were also associated with AD, which sheds light on the grey-matter markers of disease stages, and their relationship with cognitive or functional impairment. Our multi-cohort approach provides robust and fine-grained maps the grey-matter structures associated with AD, symptoms, and progression, and calls for even larger initiatives to unveil the full complexity of grey-matter structure in AD.

Aims: People with intellectual disability experience stark health inequalities, often because of poor access to mainstream healthcare. This scoping review aimed to identify factors that influence access to healthcare for people with intellectual disability using Levesque and colleagues’ comprehensive framework of healthcare access. Method: This review followed Joanna Briggs Institute guidelines. Articles were identified and retrieved from CINAHL, PsycINFO, PubMed and EMBASE. Two reviewers completed abstract and full-text screening, addressing any conflicts at each stage. Data was extracted and coded deductively, according to the supply (healthcare provider) and demand (healthcare seeker) dimensions of Levesque and colleagues’ framework. Results: Following search and screening, 66 references were included for review. Barriers to healthcare were more frequently identified in the literature compared to facilitators, with most information relating to supply-side dimensions. Barriers were related to inaccessible health information, low health literacy, stigma and discrimination by healthcare providers, and lack of organisational support, training and resourcing in both healthcare and support sectors. Facilitators often involved specialist workforces, strong interpersonal skills among healthcare providers, and advocacy from supporters. Importantly, findings indicated that both sociohistorical processes and support networks are necessary to understanding access experiences for people with intellectual disability. Conclusions: Greater efforts are required internationally to ensure the health rights of people with intellectual disability, to eliminate discrimination, and provide the support and resources necessary for all stakeholders to facilitate healthcare access. Models of healthcare access for people with intellectual disability should consider both the role of supporters and the sociohistorical context within which healthcare access occurs.

Background:Autistic people are at significant risk for suicidal thoughts and behaviors (STBs) and nonsuicidal self-injury (NSSI). We examined STB and NSSI in different age-groups, considering sex- and age-based effects, in a pooled multinational sample of English-speaking autistic children and adults. Methods:We administered the Columbia-Suicide Severity Rating Scale to 245 autistic people without intellectual disability (139 youth and 106 adults; 46.1% female sex; M age = 24.8, SD age = 16.3 years, range = 7-70) or their caregivers in Australia, Canada, and the United States. The study samples were enriched with autistic people experiencing depression and suicidality. Results:Most participants (87.8%) reported suicidal ideation and NSSI (56.3%). Nearly one-third of autistic people (31.0%) reported a lifetime suicide attempt (M = 2.9 attempts; range = 1-26); overdosing was the most common method of suicide attempt. Sex was not a significant risk factor for suicidal ideation, behavior, or NSSI. Increases in lifetime suicidal ideation were observed across older age-groups, with those aged over 18 years reporting more severe and longer-lasting ideation than in children or adolescents. The youngest age of suicide attempt was 7 years in this sample, and the average ages of first/initial, most lethal, and most recent suicide attempts in youth (n = 24) and adults (n = 42) were 16.6, 19.2, and 20.8 years old, respectively. Conclusion:Regardless of age-group, autistic people across the lifespan constitute a high-priority group for suicide prevention strategies, development of appropriate assessments, and evaluation of system-level programs that effectively address the problem of preventable death by suicide.

Public health campaigns, including Australian cancer screening programs, are increasingly promoted online through government websites. The accessibility of these initiatives for people with intellectual disability is unknown. However, a lack of accessible information about available services is an important barrier to cancer screening for this group. This study aimed to investigate the accessibility of online information for cancer screening programs. Australian government health websites promoting the national breast, bowel, and cervical screening programs were identified and web pages were evaluated for their compliance with Web Content Accessibility Guidelines 2.0, cognitive accessibility guidelines, readability recommendations, and where relevant, compliance with Easy Read guidelines. The most common accessibility errors included low-contrast colors, missing alternative text, broken links, and excessive content. Readability was a consistent issue, with most materials written at levels considered too high for both people with intellectual disability and the general population. The limited number of documents that were readily available in Easy Read did not follow guidelines. These findings demonstrate that government public health initiatives currently fail to meet the communication and information needs of people with intellectual disability. This places the population at risk of continued under-screening and fails to uphold their right to information about their healthcare. The creation and dissemination of accessible materials should be a priority for governments and health services.

BACKGROUND:Mental health disorders and adverse childhood experiences (ACEs) are known risk factors for youth offending. However, most studies operationalize these factors as static and fail to distinguish between isolated reoffences and escalating patterns of criminal behaviour. The impact of mental health service engagement on interrupting cyclical, repetitive offending also remains unclear. METHODS:We linked offending records (1994-2022) and mental health records (2001-2022) for 1556 justice-involved youth in New South Wales, Australia. The Prentice, Williams, and Peterson Gap Time model with time-varying effects was used to identify factors associated with accelerated reoffending during a five-year follow-up. RESULTS:The median age at first conviction was 15 years for custody-supervised youth and 16 years for community-supervised youth. Among custody-supervised youth aged 14 to 17, the prevalence of ACEs, mental health disorders, and their co-occurrence were 69.6 %, 33.9 %, and 26.5 %, respectively, compared to 42.5 %, 30.8 %, and 14.8 % for community-supervised youth. Recurrent offences occurred in 64.8 % of custody-supervised youth and 52.1 % of community-supervised youth. Age, physical neglect, substance use disorders, and personality disorders demonstrated time-varying effects on reoffending risk. Additional risk factors included physical abuse, parental death, anxiety disorders, mood disorders, and previous incarceration. Mental health service contact was associated with reduced reoffending risk. CONCLUSIONS:This study demonstrates the dynamic nature of criminogenic risk factors and the protective effect of mental health service engagement. Youth justice policymakers should prioritize regular mental health assessments and improved access to interventions for justice-involved youth to reduce recurrent offending and enhance public safety.

There is little nursing research about process issues in conducting inclusive project advisory groups of people with autism and/or intellectual disability or those who are parents/carers of this cohort. Through a descriptive qualitative design, this article aims to analyze the processes, challenges, and solutions when facilitating these groups for a nursing project in Australia. Reflexive thematic analysis was utilized to analyze field notes and meeting minutes. Results highlight the need for a defined, robust communication process between researchers and advisory groups, skilled facilitators, and careful planning of when in the life of the project the groups can contribute meaningfully. This project offers a proposed framework for the valuable contribution of lived experiences from research advisory groups.

The distribution of specialist health services is usually uneven by location due to limited resources, which is a problem for people with complex needs. In this context, how can a hub and spoke model offer appropriate services for people with intellectual disability and mental health needs? The data were individual and group interviews with people using and delivering the services in Australia. Data were analysed against a hub-and-spoke analytical framework. The findings were that health services benefited from funded, local positions. These local professionals liaised between local mental health, health and disability providers. They also liaised with other local areas and centralised, specialist intellectual disability mental health services. The implication is that specific local positions can be a bridge between generic and specialist services to improve services for people with specific support needs. This program worked well in a geographically large area with a scattered population and decentralised health system.

OBJECTIVES:To estimate point prevalence of apathy in older adults, examine its overlap with depression and fatigue, and explore its associations with multimorbidity and objective markers of health. DESIGN:Sydney Memory and Ageing Study, an Australian population-based cohort. SETTING:Community dwellings between 2005-2007. PARTICIPANTS:1,030 older adults, without dementia, aged 70-90. MEASUREMENTS:Apathy was classified using strict (=3) and standard (≥2) cutoff scores on the self-report Geriatric Depression Scale (GDS)-3A, and a validated cutoff score (>0) on the informant-report Neuropsychiatric Inventory. Depression was assessed with strict and standard cutoffs on the GDS-12D, and fatigue with the Assessment of Quality of Life-6D. Multimorbidity (≥2 chronic conditions; computed with and without cardiovascular conditions), physical performance (walking speed, sit-to-stand, lateral stability, grip strength), adiposity (BMI, waist circumference), blood pressure, cholesterol and glucose were assessed. RESULTS:Prevalence of apathy on the self-reported measure was 15.8 % (strict cutoff) or 48.9 % (standard). Informant-reported apathy was lower (2.9 %). Prevalence of self-reported depression was 5.9 % (strict cutoff) or 15.8 % (standard), and fatigue 9.8 %. Apathy overlapped very little with depression or fatigue (κ = .18, 95 % CI .14-.21). Apathy was associated with multimorbidity (even when excluding cardiovascular conditions), adiposity, fasting blood glucose level and physical performance, but not blood pressure or cholesterol. CONCLUSIONS:Apathy is more common than depression or fatigue in dementia-free older adults. It does not typically co-occur with these symptoms, but is accompanied by poorer physical health, including multimorbidity and metabolic dysregulation. Apathy may be relevant for public health and an important consideration in clinical care.

As the number of older autistic adults and adults with intellectual disabilities grows, expanding capacity to meet their needs is crucial. On November 23-25, 2023, a Think Tank on aging in autism and/or intellectual disabilities was convened, with national and international delegates within this field. The Think Tank consisted of presentations focusing on key issues as well as a series of panel presentations addressing first-person lived experience, family caregiving, service provision in the community, and physical and mental health-based care. Discussion reflected lived experiences and care needs in this population, with an ultimate aim of advancing healthcare and community support. Delegates, who represent perspectives as self-advocates, family caregivers, service providers, clinicians and researchers, ranked guidelines and areas of focus identified in the literature in terms of the most important priorities for the near-term development of capacity building resources.

The concept of person-centred care is embraced internationally as a fundamental aspiration for nursing and health professions more broadly. For many, person-centred care is seen as a fundamental part of the art of nursing. The available research suggests that while an aspiration of the profession, person-centred care is not actual nursing practice. A limited body of research has identified positive impacts on patient outcomes attributable to person-centred care. In the context of care for people with autism and/or intellectual disability, reasonable adjustments are an example of person-centred care. This national cross-sectional survey aimed to determine the degree of awareness of the concept of reasonable adjustments, the types of self-reported adjustments made, and the relationship between making adjustments and the individual factors of self-efficacy, ambivalence, and role autonomy. From the 422 Australian registered nurse respondents, it was identified that 54% of respondents were aware of the concept of reasonable adjustments, and the majority did not report making person-centred adjustments to practice for this group. Further, it was found that people with autism and/or intellectual disability are least likely to experience person-centred care in acute hospitals and aged care contexts. It was identified that person-centred care, indicated by the example of reasonable adjustments, is not the predominant current model of care as self-reported by registered nurses in Australia. This is contrary to the current national standards for practice.

ObjectivesTo determine bidirectional relationships between incarceration and mental disorders. We hypothesized that (1) pre-existing mental disorders would be associated with increased incarceration risk, and (2) incarceration would be associated with increased incident mental disorder diagnosis risk in adolescents without prior psychiatric diagnosis.MethodThis retrospective cohort study included 1551 adolescents (aged 10-17 years) from four New South Wales (NSW) health surveys linked to justice and health records. Modified Poisson regression examined associations between pre-existing mental disorders and incarceration. Prentice-Williams-Peterson Total-Time models examined associations between time-varying incarceration exposure and incident mental disorder diagnoses among those without prior diagnosis.ResultsAmong 1551 adolescents (87.7% male; median age 15 years), pre-existing mental disorders were associated with an increased incarceration risk (adjusted Risk Ratio [RR]: 1.26, 95% Confidence Interval [CI]: 1.09-1.45), which was more pronounced among those with violent offences. Among 1424 adolescents without prior diagnosis, incarceration was associated with increased incident diagnosis risk (adjusted Hazard Ratio [aHR]: 1.22, 95% CI: 1.09-1.37), with stronger associations among adolescents residing in areas of higher socioeconomic disadvantage.ConclusionsFindings suggest incarceration may be associated with adverse mental health outcomes, with implications for diversionary pathways and custodial mental health care.

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect. Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods. We combined data from 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct one of the largest genome-wide association study meta-analyses of monozygotic phenotypic differences, in children, adolescents and adults separately, for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism and wellbeing. The proportions of phenotypic variance explained by single-nucleotide polymorphisms in these phenotypes were estimated (h2 = 0-18%), but were imprecise. We identified 13 genome-wide significant associations (single-nucleotide polymorphisms, genes and gene sets), including genes related to stress reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. This is the largest genetic study of monozygotic twins to date by an order of magnitude, evidencing an alternative method to study the genetic architecture of environmental sensitivity. The statistical power was limited for some analyses, calling for better-powered future studies.

BACKGROUND:People with intellectual disability are disproportionately affected by mental illness, including serious mental illness. While the prevalence of mental illness in this population is well-documented, the factors associated with the onset of any mental illness and serious mental illness lack comprehensive investigation. This study aims to identify demographic, service-related and disability-related factors associated with the onset of any mental illness and serious mental illness in people with intellectual disability using a large, linked dataset in New South Wales, Australia. METHODS:A retrospective cohort study was conducted using linked administrative data for 47,330 individuals with intellectual disability aged 13-80 years. Data from 2004 to 2018 were used to track first recorded contact with mental health services for any mental illness and serious mental illness. Flexible parametric survival analysis was employed to account for time-varying factors and estimate hazard ratios for the risk of developing any mental illness or serious mental illness. RESULTS:Nearly half of the cohort (48.9%) experienced any mental illness, and 11.7% experienced serious mental illness. Factors associated with any mental illness included attention-deficit/hyperactivity disorder, learning disorders, physical comorbidities, and living in areas of greater socioeconomic disadvantage. Serious mental illness onset was associated with living in outer regional, remote or very remote areas, attention-deficit/hyperactivity disorder, learning disorders, male sex, and a history of any mental illness. CONCLUSION:This study identified factors associated with the onset of any mental illness and serious mental illness in people with intellectual disability. These findings emphasise the need for early identification and targeted interventions to improve mental health outcomes in this high-risk population.