Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Longitudinal symptomatic interactions in long-standing schizophrenia: a novel five-point analysis based on directed acyclic graphs.

BACKGROUND: Recent network models propose that mutual interaction between symptoms has an important bearing on the onset of schizophrenic disorder. In particular, cross-sectional studies suggest that affective symptoms may influence the emergence of psychotic symptoms. However, longitudinal analysis offers a more compelling test for causation: the European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. We predicted that the persistence of psychotic symptoms would be driven by the continuing presence of affective disturbance. METHODS: EuroSC included 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures of psychotic and affective symptoms were repeated four times at 6-month intervals, thereby furnishing five time-points. To examine interactions between symptoms both within and between time-slices, we adopted a novel technique for modelling longitudinal data in psychiatry. This was a form of Bayesian network analysis that involved learning dynamic directed acyclic graphs (DAGs). RESULTS: Our DAG analysis suggests that the main drivers of symptoms in this long-term sample were delusions and paranoid thinking. These led to affective disturbance, not vice versa as we initially predicted. The enduring relationship between symptoms was unaffected by whether patients were receiving first- or second-generation antipsychotic medication. CONCLUSIONS: In this cohort of people with chronic schizophrenia treated with medication, symptoms were essentially stable over long periods. However, affective symptoms appeared driven by the persistence of delusions and persecutory thinking, a finding not previously reported. Although our findings as ever remain hostage to unmeasured confounders, these enduring psychotic symptoms might nevertheless be appropriate candidates for directly targeted psychological interventions.

Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium.

Introduction: Coronavirus disease 2019 (COVID-19) has caused >3.5 million deaths worldwide and affected >160 million people. At least twice as many have been infected but remained asymptomatic or minimally symptomatic. COVID-19 includes central nervous system manifestations mediated by inflammation and cerebrovascular, anoxic, and/or viral neurotoxicity mechanisms. More than one third of patients with COVID-19 develop neurologic problems during the acute phase of the illness, including loss of sense of smell or taste, seizures, and stroke. Damage or functional changes to the brain may result in chronic sequelae. The risk of incident cognitive and neuropsychiatric complications appears independent from the severity of the original pulmonary illness. It behooves the scientific and medical community to attempt to understand the molecular and/or systemic factors linking COVID-19 to neurologic illness, both short and long term. Methods: This article describes what is known so far in terms of links among COVID-19, the brain, neurological symptoms, and Alzheimer's disease (AD) and related dementias. We focus on risk factors and possible molecular, inflammatory, and viral mechanisms underlying neurological injury. We also provide a comprehensive description of the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2) harmonized methodology to address these questions using a worldwide network of researchers and institutions. Results: Successful harmonization of designs and methods was achieved through a consensus process initially fragmented by specific interest groups (epidemiology, clinical assessments, cognitive evaluation, biomarkers, and neuroimaging). Conclusions from subcommittees were presented to the whole group and discussed extensively. Presently data collection is ongoing at 19 sites in 12 countries representing Asia, Africa, the Americas, and Europe. Discussion: The Alzheimer's Association Global Consortium harmonized methodology is proposed as a model to study long-term neurocognitive sequelae of SARS-CoV-2 infection. Key Points: The following review describes what is known so far in terms of molecular and epidemiological links among COVID-19, the brain, neurological symptoms, and AD and related dementias (ADRD)The primary objective of this large-scale collaboration is to clarify the pathogenesis of ADRD and to advance our understanding of the impact of a neurotropic virus on the long-term risk of cognitive decline and other CNS sequelae. No available evidence supports the notion that cognitive impairment after SARS-CoV-2 infection is a form of dementia (ADRD or otherwise). The longitudinal methodologies espoused by the consortium are intended to provide data to answer this question as clearly as possible controlling for possible confounders. Our specific hypothesis is that SARS-CoV-2 triggers ADRD-like pathology following the extended olfactory cortical network (EOCN) in older individuals with specific genetic susceptibility.The proposed harmonization strategies and flexible study designs offer the possibility to include large samples of under-represented racial and ethnic groups, creating a rich set of harmonized cohorts for future studies of the pathophysiology, determinants, long-term consequences, and trends in cognitive aging, ADRD, and vascular disease.We provide a framework for current and future studies to be carried out within the Consortium. and offers a "green paper" to the research community with a very broad, global base of support, on tools suitable for low- and middle-income countries aimed to compare and combine future longitudinal data on the topic.The Consortium proposes a combination of design and statistical methods as a means of approaching causal inference of the COVID-19 neuropsychiatric sequelae. We expect that deep phenotyping of neuropsychiatric sequelae may provide a series of candidate syndromes with phenomenological and biological characterization that can be further explored. By generating high-quality harmonized data across sites we aim to capture both descriptive and, where possible, causal associations.

Intimate partner violence, suicidality, and self-harm: a probability sample survey of the general population in England.

BACKGROUND: Intimate partner violence (IPV) is a recognised risk factor for psychiatric disorders. There is little current evidence on IPV and self-harm and suicidality, and we therefore aimed to investigate the associations between experience of lifetime and past-year IPV with suicidal thoughts, suicide attempt, and self-harm in the past year. METHODS: We analysed the 2014 Adult Psychiatric Morbidity Survey, a cross-sectional survey of 7058 adults (aged ≥16 years) in England, which used a multistage random probability sampling design and involved face-to-face interviews. Participants were asked about experience of physical violence and sexual, economic, and emotional abuse from a current or former partner, and about suicidal thoughts, suicide attempts, and self-harm. Other adversities were recorded through an adapted version of the List of Threatening Experiences. Multivariable logistic regression models quantified associations between different indicators of lifetime and past-year IPV, with past-year non-suicidal self-harm, suicidal thoughts, and suicide attempts. All analyses were weighted. FINDINGS: Using weighted percentages, we found that a fifth (21·4%) of 7058 adults reported lifetime experience of IPV, and that 27·2% of women and 15·3% of men had experienced IPV. Among women, 19·6% had ever experienced emotional IPV, 18·7% physical IPV, 8·5% economic IPV, and 3·7% sexual IPV, which was higher than in men (8·6%, 9·3%, 3·6%, and 0·3%, respectively). Findings for ethnicity were unclear. Lifetime prevalence of IPV was higher in those living in rented accommodation or deprived neighbourhoods. Among people who had attempted suicide in the past year, 49·7% had ever experienced IPV and 23·1% had experienced IPV in the past year (including 34·8% of women and 9·4% of men). After adjusting for demographics, socioeconomics, and lifetime experience of adversities, the odds ratio of a past-year suicide attempt were 2·82 (95% CI 1·54-5·17) times higher in those who have ever experienced IPV, compared with those who had not. Fully adjusted odds ratios for past-year self-harm (2·20, 95% CI 1·37-3·53) and suicidal thoughts (1·85, 1·39-2·46) were also raised in those who had ever experienced IPV. INTERPRETATION: IPV is common in England, especially among women, and is strongly associated with self-harm and suicidality. People presenting to services in suicidal distress or after self-harm should be asked about IPV. Interventions designed to reduce the prevalence and duration of IPV might protect and improve the lives of people at risk of self-harm and suicide. FUNDING: UK Prevention Research Partnership.

Influence of positive and negative symptoms on hedonic and eudaemonic well-being in people with schizophrenia: A longitudinal analysis from the EuroSc study.

BACKGROUND: Subjective well-being in people with schizophrenia is likely to be impaired by positive and negative psychotic symptoms. However, these may impact differentially on hedonic (satisfaction and interest in life) and eudaemonic (optimal psychological and social functioning) components. AIMS: We hypothesized that positive symptoms would influence the hedonic component, while negative symptoms would be linked to eudaemonic well-being. METHODS: We tested this using longitudinal data (N = 1208) from the EUROSC study. Measures were repeated after 6, 12, 18 and 24 months. Hedonic and eudaemonic features were identified using the Quality of Life Interview. Positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale. We used latent variable structural equation modelling to investigate the impact of positive and negative symptoms at each of the four data points on well-being components 6 months later, controlling for depressed mood. RESULTS: The measurement model yielded acceptable fit. People with higher scores on positive symptoms at a given time-point were more likely to report lower scores for hedonic components six months later (6-, 12-, and 24-month), whereas we found no significant paths from negative symptoms to hedonic or eudaemonic features. CONCLUSIONS: Although we found a longitudinal influence of positive symptoms on hedonic well-being, negative symptoms had no effect on either hedonic or eudaemonic components. While symptom reduction strategies may be helpful for hedonic well-being, the amelioration of eudaemonic features may require targeted psychosocial programmes to help individuals attain more rewarding lives.

Association of Task-Shared Psychological Interventions With Depression Outcomes in Low- and Middle-Income Countries: A Systematic Review and Individual Patient Data Meta-analysis.

Importance: Task sharing, the training of nonspecialist workers with no formal experience in counseling, is a promising strategy for addressing the large gap in treatment for depression in low- and middle-income countries (LMICs). Objective: To examine the outcomes and moderators of task-shared psychological interventions associated with depression severity, response, and remission. Data Sources: Systematic literature searches in PubMed, Embase, PsycINFO, and Cochrane Library up to January 1, 2021. Study Selection: Randomized clinical trials (RCTs) of task-shared psychological interventions compared with control conditions for adults with depressive symptoms in LMICs were included. Data Extraction and Synthesis: Two researchers independently reviewed the titles, abstracts, and full text of articles from an existing generic meta-analytic database that includes all RCTs on psychotherapy for depression. A systematic review and individual patient data (IPD) meta-analysis was used to estimate the outcomes of task-shared psychological interventions across patient characteristics using mixed-effects models. Procedures for abstracting data and assessing data quality and validity followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Main Outcomes and Measures: Primary outcome was reduction in depression symptom severity measured by the 9-item Patient Health Questionnaire (PHQ-9). Response and remission rates were also estimated. Results: Of 13 eligible trials, 11 (4145 participants) contributed IPD. Task-shared psychological interventions were associated with a greater decrease in depressive symptom severity than control conditions (Hedges g, 0.32; 95% CI, -0.26 to -0.38). Participants in the intervention groups had a higher chance of responding (odds ratio, 2.11; 95% CI, 1.60 to 2.80) and remitting (odds ratio, 1.87; 95% CI, 1.20 to 1.99). The presence of psychomotor symptoms was significantly associated with the outcomes of task-shared psychological interventions (ß [SE], -1.21 [0.39]; P = .002). No other significant associations were identified. Heterogeneity among the trials with IPD was 74% (95% CI, 53%-86%). Conclusions and Relevance: In this meta-analysis of IPD, task-shared psychological interventions were associated with a larger reduction in depressive symptom severity and a greater chance of response and remission than control conditions. These findings show potential for the use of task-sharing of psychological interventions across different groups of patients with depression. Further research would help identify which people are most likely to benefit and strengthen larger-scale implementation of this strategy to address the burden of depression in LMICs.

The chronic neuropsychiatric sequelae of COVID-19: The need for a prospective study of viral impact on brain functioning.

INTRODUCTION: The increasing evidence of SARS-CoV-2 impact on the central nervous system (CNS) raises key questions on its impact for risk of later life cognitive decline, Alzheimer's disease (AD), and other dementia. METHODS: The Alzheimer's Association and representatives from more than 30 countries-with technical guidance from the World Health Organization-have formed an international consortium to study the short-and long-term consequences of SARS-CoV-2 on the CNS-including the underlying biology that may contribute to AD and other dementias. This consortium will link teams from around the world covering more than 22 million COVID-19 cases to enroll two groups of individuals including people with disease, to be evaluated for follow-up evaluations at 6, 9, and 18 months, and people who are already enrolled in existing international research studies to add additional measures and markers of their underlying biology. CONCLUSIONS: The increasing evidence and understanding of SARS-CoV-2's impact on the CNS raises key questions on the impact for risk of later life cognitive decline, AD, and other dementia. This program of studies aims to better understand the long-term consequences that may impact the brain, cognition, and functioning-including the underlying biology that may contribute to AD and other dementias.

The Early Impact of the COVID-19 Pandemic on Acute Care Mental Health Services.

OBJECTIVE: This study aimed to explore the effects of COVID-19 and the lockdown measures adopted in England on patients with acute mental illness. METHODS: The authors analyzed referrals to the crisis resolution and home treatment (CRHT) team and inpatient admissions to acute adult wards, at Leicestershire Partnership National Health Service Trust, an integrated community and mental health trust in the United Kingdom. Number of CRHT referrals and inpatient admissions during a 4-week period starting March 16, 2020 ("COVID-19 period"), was studied and compared with the same period in 2018 and 2019 ("control periods"). Demographic and clinical characteristics of patients admitted during the COVID-19 period were compared with those admitted during the 2019 control period. RESULTS: The number of CRHT referrals and inpatient admissions were lower during the COVID-19 period, compared with the control periods, by approximately 12% and 20%, respectively. Patients admitted during the COVID-19 period were significantly more often detained under the Mental Health Act and were considered to pose a risk of aggression. The pattern of diagnoses differed significantly between 2020 and 2019. A higher percentage of patients admitted during the COVID-19 period were diagnosed as having nonaffective psychotic disorders (52% versus 35%) or bipolar disorder (25% versus 15%), and fewer received a diagnosis of depression (8% versus 16%), anxiety disorder (0% versus 3%), adjustment disorder (0% versus 8%), emotionally unstable personality disorder (6% versus 15%), or any other personality disorder (0% versus 5%) (p=0.01). CONCLUSIONS: These findings suggest that the pandemic has profoundly affected care by acute mental health services.

Autism spectrum disorder.

Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.

Testing adults by questionnaire for social and communication disorders, including autism spectrum disorders, in an adult mental health service population.

OBJECTIVES: Autism is difficult to identify in adults due to lack of validated self-report questionnaires. We compared the effectiveness of the autism-spectrum quotient (AQ) and the Ritvo autism-Asperger's diagnostic scale-revised (RAADS-R) questionnaires in adult mental health services in two English counties. METHODS: A subsample of adults who completed the AQ and RAADS-R were invited to take part in an autism diagnostic observation schedule (ADOS Module 4) assessment with probability of selection weighted by scores on the questionnaires. RESULTS: There were 364 men and 374 women who consented to take part. Recorded diagnoses were most commonly mood disorders (44%) and mental and behavioural disorders due to alcohol/substance misuse (19%), and 4.8% (95% CI [2.9, 7.5]) were identified with autism (ADOS Module 4 10+). One had a pre-existing diagnosis of autism; five (26%) had borderline personality disorders (all female) and three (17%) had mood disorders. The AQ and RAADS-R had fair test accuracy (area under receiver operating characteristic [ROC] curve 0.77 and 0.79, respectively). AQ sensitivity was 0.79 (95% CI [0.54, 0.94]) and specificity was 0.77 (95% CI [0.65, 0.86]); RAADS-R sensitivity was 0.75 (95% CI [0.48, 0.93]) and specificity was 0.71 (95% CI [0.60, 0.81]). CONCLUSIONS: The AQ and RAADS-R can guide decisions to refer adults in mental health services to autism diagnostic services.

The Prevalence of Diabetes in Autistic Persons: A Systematic Review.

BACKGROUND: It has been proposed that autistic individuals are at an increased risk of type 1 and type 2 diabetes. Improved understanding of diabetes prevalence in autistic persons will help inform resource allocation for diabetes-related public health measures for this patient group. OBJECTIVE: To conduct a systematic review of published literature pertaining to type 1 and type 2 diabetes prevalence in autistic individuals, including comparison with their non-autistic peers. METHODS: Eligibility criteria included studies investigating the prevalence of diabetes in autistic individuals, as well as having been published in the English language. A systematic search of online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and PubMed) was conducted on 4th April 2020. Additional approaches included the ancestry method, grey literature searches and expert consultation. Studies were qualitatively analysed with reporting quality appraised. RESULTS: 19 eligible studies were identified, 7 of which provided type-specific diabetes prevalence data. Of 15 studies that included a non-autistic control group, 9 reported a higher diabetes prevalence among autistic persons, with a statistically significant difference in 4 studies. Studies demonstrating a higher diabetes prevalence in autistic groups had higher average study population sizes and reporting quality ratings. CONCLUSION: It is uncertain whether diabetes is significantly more prevalent in autistic persons relative to their non-autistic peers, though larger studies suggest a trend in this direction. Nevertheless, diabetes is a significant public health issue for the autistic community, which may require a tailored approach for identification and management. Prospero database registration number: CRD42019122176.

The mediating role of depression in pathways linking positive and negative symptoms in schizophrenia. A longitudinal analysis using latent variable structural equation modelling.

BACKGROUND: The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms. METHODS: We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months. RESULTS: We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct. CONCLUSIONS: Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

Psychotic symptoms and sensory impairment: Findings from the 2014 adult psychiatric morbidity survey.

PURPOSE: Hearing and visual impairment have been associated with psychosis. Mechanisms behind this are poorly understood. We tested whether i) self-reported hearing and visual impairments are associated with psychotic symptoms in the 2014 UK Adult Psychiatric Morbidity Survey; ii) the odds of having psychotic symptoms vary with self-perceived degree of impairments; and iii) reduced social functioning partially explains these associations. METHODS: We analysed cross-sectional data using logistic regression. Hearing and visual impairment were the exposures, and screening positive on the Psychosis Screening Questionnaire was the outcome. We used structural equation modelling to assess mediation by social functioning, measured by the Social Functioning Questionnaire. RESULTS: Psychotic symptoms were strongly associated with visual impairment (Adjusted Odds Ratio (AOR) 1.81, 95% Confidence Intervals (CI) 1.33 to 2.44), especially moderate visual impairment (AOR 2.75, 95% CI 1.78 to 4.24, p < .001). Psychotic symptoms were associated with a severe degree of hearing impairment (AOR 4.94, 95% CI 1.66 to 14.67, p = .004), and weakly associated with hearing impairment overall (AOR 1.50, 95% CI 1.10 to 2.04, p = .010). Social functioning accounted for approximately 50% of associations with both types of sensory impairment, but the confidence intervals around these estimates were broad. CONCLUSIONS: Our findings suggest an association between psychosis and visual impairment, with the strongest evidence for moderate visual impairment; the findings also support a linear relationship between psychosis and degree of hearing impairment. Social functioning may mediate these relationships and be a potential target for intervention, alongside sensory correction. These should be investigated longitudinally.

Study protocol: an investigation of the prevalence of autism among adults admitted to acute mental health wards: a cross-sectional pilot study.

INTRODUCTION: Autism spectrum disorders (ASDs) are associated with difficulties in social interaction, communication and restricted, repetitive behaviours. Much is known about their community prevalence among adults, data on adult inpatients within an acute mental health setting is lacking.This pilot study aimed to estimate the prevalence of ASDs among adults admitted to acute mental health wards and to examine the association between ASDs and psychiatric and physical comorbidities within this group. METHODS AND ANALYSIS: A multiple-phase approach will be used. Phase I will involve testing of 200 patients and corresponding informants, using the autism quotient (AQ), the informant version of the Social Responsiveness Scale, second edition-Adult, the self and informant versions of the Adult Social Behaviour Questionnaire and the EuroQol-5D-5L. Patients with intellectual disability (ID) will bypass Phase I.Phase II will involve diagnostic testing of a subgroup of 40 patients with the Diagnostic Interview for Social and Communication Disorders, the Autism Diagnostic Observation Schedule version 2 and the ASD interview within the Schedules for Clinical Assessment in Neuropsychiatry version 3. 25±5 patients will not have ID and be selected via stratified random sampling according to AQ score; 15±5 patients will have ID. Phase II patients will be interviewed with the Physical Health Conditions and Mental Illness Diagnoses and Treatment sections of the 2014 Adult Psychiatric Morbidity Survey.Prevalence estimates will be based on the proportion of Phase II participants who satisfy the 10th revision of the International Statistical Classification of Diseases and Related Health Problems Diagnostic Criteria for Research (ICD-10-DCR) and the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for ASD, adjusting for selection and non-response. Univariate analysis will be conducted for comorbidities to identify the level of their association with an ASD diagnosis. ETHICS AND DISSEMINATION: Study oversight is provided by the University of Leicester. The National Health Service Health Research Authority have provided written approval. Study results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN27739943.

Prevalence of non-suicidal self-harm and service contact in England, 2000-14: repeated cross-sectional surveys of the general population.

BACKGROUND: The number of people presenting to hospital emergency departments after self-harming has increased in England. However, most people who self-harm do not present to hospitals, so whether this rise reflects an increase in the prevalence of self-harm in the community is unknown. Also unknown is whether the prevalence of non-suicidal self-harm (NSSH) or suicidal self-harm, or both, has increased. We aimed to establish temporal trends in the prevalence of NSSH in England. METHODS: We analysed data from participants in the 2000 (n=7243), 2007 (n=6444), and 2014 (n=6477) Adult Psychiatric Morbidity Surveys of the general population, selecting those aged 16-74 years and living in England. We used weighted data and controlled for complex survey design. We generated temporal trends in lifetime prevalence and methods of, and motivations for, NSSH, and consequent service contact. We used multiple variable logistic regression analyses to investigate factors associated with service contact. FINDINGS: The prevalence of self-reported lifetime NSSH increased from 2·4% (95% CI 2·0-2·8) in 2000, to 6·4% (5·8-7·2) in 2014. Increases in prevalence were noted in both sexes and across age groups-most notably in women and girls aged 16-24 years, in whom prevalence increased from 6·5% (4·2-10·0) in 2000, to 19·7% (15·7-24·5) in 2014. The proportion of the population reporting NSSH to relieve unpleasant feelings of anger, tension, anxiety, or depression increased from 1·4% (95% CI 1·0-2·0) to 4·0% (3·2-5·0) in men and boys, and from 2·1% (1·6-2·7) to 6·8% (6·0-7·8) in women and girls, between 2000 and 2014. In 2014, 59·4% (95% CI 54·7-63·9) of participants who had engaged in NSSH reported no consequent medical or psychological service contact, compared with 51·2% (42·2-60·0) in 2000 and 51·8% (47·3-56·4) in 2007. Male participants and those aged 16-34 years were less likely to have contact with health services than were female participants and older people. INTERPRETATION: The prevalence of NSSH has increased in England, but resultant service contact remains low. In 2014, about one in five female 16-24-year-olds reported NSSH. There are potential lifelong implications of NSSH, such as an increased frequency of suicide, especially if the behaviours are adopted as a long-term coping strategy. Self-harm needs to be discussed with young people without normalising it. Young people should be offered help by primary care, educational, and other services to find safer ways to deal with emotional stress. FUNDING: NHS Digital, English Department of Health and Social Care, and the National Institute for Health Research.

The relationship between symptoms of autism spectrum disorder and visual impairment among adults with intellectual disability.

The higher prevalence of autism reported in blind children has been commonly attributed to the confounding effects of an underlying intellectual disability. The aim of this study was to explore the relationship between symptoms of autism and blindness in adults with intellectual disability. We hypothesized that blindness can increase the probability of the autism phenotype, independent of known risk factors, that is, severity of intellectual disability and gender. A general population case register (population size of 0.7 million) was used to conduct two studies. The first study was on 3,138 adults with intellectual disability, using a validated autism risk indicator to study adults with visual impairment. This identified 386 adults with partial and complete visual impairment, both of which were associated with presence of high number of autistic traits (P < 0.001). The second study was only on those with congenital blindness using a standardized assessment tool, the Pervasive Developmental Disorder-Mental Retardation Scale. Those with hearing impairment or unilateral, partial, and acquired visual impairment were excluded. Control groups were randomly selected from those with normal hearing and vision. Prevalence of the autism phenotype was higher among those with congenital blindness (n = 46/60; 76.7%) than their controls (n = 36/67; 53.7%) and this association was statistically significant (adjusted odds ratio = 3.03; 95% confidence interval: 1.34-6.89; P = 0.008). Our results support the hypothesis that a congenital blindness independently affects psychosocial development and increases the probability of the autism phenotype. Early identification of autism could facilitate appropriate psychosocial interventions and educational opportunities to improve quality of life of people with blindness. Autism Res 2019, 12: 1411-1422. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Although autism has been commonly reported in those with blindness, it is generally attributed to an accompanying intellectual disability. Current study, however, revealed that congenital blindness is independently associated with symptoms of autism. In spite of its high prevalence, autism can be overlooked in those with intellectual disability and blindness. Improving diagnosis in this population should, therefore, be advocated through raising awareness of this association to facilitate early access to services.

Cost-effectiveness of PoNDER health visitor training for mothers at lower risk of depression: findings on prevention of postnatal depression from a cluster-randomised controlled trial.

BACKGROUND: There is evidence for the cost-effectiveness of health visitor (HV) training to assess postnatal depression (PND) and deliver psychological approaches to women at risk of depression. Whether this approach is cost-effective for lower-risk women is unknown. There is a need to know the cost of HV-delivered universal provision, and how much it might cost to improve health-related quality of life for postnatal women. A sub-study of a cluster-randomised controlled trial in the former Trent region (England) previously investigated the effectiveness of PoNDER HV training in mothers at lower risk of PND. We conducted a parallel cost-effectiveness analysis at 6-months postnatal for all mothers with lower-risk status attributed to an Edinburgh Postnatal Depression Scale (EPDS) score <12 at 6-weeks postnatal. METHODS: Intervention HVs were trained in assessment and cognitive behavioural or person-centred psychological support techniques to prevent depression. Outcomes examined: quality-adjusted life-year (QALY) gains over the period between 6 weeks and 6 months derived from SF-6D (from SF-36); risk-of-depression at 6 months (dichotomising 6-month EPDS scores into lower risk (<12) and at-risk (⩾12). RESULTS: In lower-risk women, 1474 intervention (63 clusters) and 767 control participants (37 clusters) had valid 6-week and 6-month EPDS scores. Costs and outcomes data were available for 1459 participants. 6-month adjusted costs were £82 lower in intervention than control groups, with 0.002 additional QALY gained. The probability of cost-effectiveness at £20 000 was very high (99%). CONCLUSIONS: PoNDER HV training was highly cost-effective in preventing symptoms of PND in a population of lower-risk women and cost-reducing over 6 months.