Approaches to improving mental health care for autistic children and young people: a systematic review and meta-analysis.

Autistic children and young people (CYP) experience mental health difficulties but face many barriers to accessing and benefiting from mental health care. There is a need to explore strategies in mental health care for autistic CYP to guide clinical practice and future research and support their mental health needs. Our aim was to identify strategies used to improve mental health care for autistic CYP and examine evidence on their acceptability, feasibility, and effectiveness. A systematic review and meta-analysis were carried out. All study designs reporting acceptability/feasibility outcomes and empirical quantitative studies reporting effectiveness outcomes for strategies tested within mental health care were eligible. We conducted a narrative synthesis and separate meta-analyses by informant (self, parent, and clinician). Fifty-seven papers were included, with most investigating cognitive behavioral therapy (CBT)-based interventions for anxiety and several exploring service-level strategies, such as autism screening tools, clinician training, and adaptations regarding organization of services. Most papers described caregiver involvement in therapy and reported adaptations to communication and intervention content; a few reported environmental adjustments. In the meta-analyses, parent- and clinician-reported outcomes, but not self-reported outcomes, showed with moderate certainty that CBT for anxiety was an effective treatment compared to any comparison condition in reducing anxiety symptoms in autistic individuals. The certainty of evidence for effectiveness, synthesized narratively, ranged from low to moderate. Evidence for feasibility and acceptability tended to be positive. Many identified strategies are simple, reasonable adjustments that can be implemented in services to enhance mental health care for autistic individuals. Notable research gaps persist, however.

Ethnic differences in receipt of psychological interventions in Early Intervention in Psychosis services in England - a cross-sectional study.

There is some evidence of differences in psychosis care provision by ethnicity. We investigated variations in the receipt of Cognitive Behavioural Therapy for psychosis (CBTp) and family intervention across ethnic groups in Early Intervention in Psychosis (EIP) teams throughout England, where national policy mandates offering these interventions to all. We included data on 29,610 service users from the National Clinical Audit of Psychosis (NCAP), collected between 2018 and 2021. We conducted mixed effects logistic regression analyses to examine odds ratios of receiving an intervention (CBTp, family intervention, either intervention) across 17 ethnic groups while accounting for the effect of years and variance between teams and adjusting for individual- (age, gender, occupational status) and team-level covariates (care-coordinator caseload, inequalities strategies). Compared with White British people, every minoritized ethnic group, except those of mixed Asian-White and mixed Black African-White ethnicities, had significantly lower adjusted odds of receiving CBTp. People of Black African, Black Caribbean, non-African/Caribbean Black, non-British/Irish White, and of "any other" ethnicity also experienced significantly lower adjusted odds of receiving family intervention. Pervasive inequalities in receiving CBTp for first episode psychosis exist for almost all minoritized ethnic groups, and family intervention for many groups. Investigating how these inequalities arise should be a research priority.

Mental health in Europe during the COVID-19 pandemic: a systematic review.

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions.

Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study.

Introduction: The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways. Methods: Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects (n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05. Results: Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [F(3,143) = 1.01, p = 0.39], hippocampus [F(3,143) = 0.63, p = 0.60] or striatum [F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs (p > 0.05). All results were robust to addition of covariates (p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses (p > 0.05FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses. Conclusion: On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

Child maltreatment investigations: Comparing children, families, and reasons for referral in three European countries.

BACKGROUND: Almost all countries have developed measures to ensure that children do not suffer from violence in their families. However, the legal framework, definitions of maltreatment, and institutional structures differ. Whereas in other areas of social policy comparative research is very common, child protection research falls behind. RESEARCH QUESTIONS: The article examines the differences between cases referred to local child and youth welfare authorities due to concerns about abuse or neglect in Germany, England and the Netherlands, comparing the characteristics of the child, the family, the person reporting the suspected maltreatment, and the type of maltreatment. METHOD: 1207 case files on children investigated due to suspected child maltreatment from the Netherlands, England, and Germany were analyzed using a standardized coding scheme. RESULTS: The family backgrounds of the children reported differed substantially, with more lone parents in England and more children living in two households in the Netherlands. The persons and institutions reporting their concerns to the local child and youth welfare authorities also differed, with more reports from children and family members in Germany and more from health services in England. In England, physical abuse, sexual abuse, and sexual exploitation were more frequently the reason for referral than in the Netherlands and Germany. DISCUSSION: Differences between countries can partially be explained based on differences in policies and relations of other systems to the child protection system.

Real-World Implementation of Precision Psychiatry: A Systematic Review of Barriers and Facilitators.

BACKGROUND: Despite significant research progress surrounding precision medicine in psychiatry, there has been little tangible impact upon real-world clinical care. OBJECTIVE: To identify barriers and facilitators affecting the real-world implementation of precision psychiatry. METHOD: A PRISMA-compliant systematic literature search of primary research studies, conducted in the Web of Science, Cochrane Central Register of Controlled Trials, PsycINFO and OpenGrey databases. We included a qualitative data synthesis structured according to the 'Consolidated Framework for Implementation Research' (CFIR) key constructs. RESULTS: Of 93,886 records screened, 28 studies were suitable for inclusion. The included studies reported 38 barriers and facilitators attributed to the CFIR constructs. Commonly reported barriers included: potential psychological harm to the service user (n = 11), cost and time investments (n = 9), potential economic and occupational harm to the service user (n = 8), poor accuracy and utility of the model (n = 8), and poor perceived competence in precision medicine amongst staff (n = 7). The most highly reported facilitator was the availability of adequate competence and skills training for staff (n = 7). CONCLUSIONS: Psychiatry faces widespread challenges in the implementation of precision medicine methods. Innovative solutions are required at the level of the individual and the wider system to fulfil the translational gap and impact real-world care.

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

Examining the variability of neurocognitive functioning in individuals at clinical high risk for psychosis: a meta-analysis.

This study aims to meta-analytically characterize the presence and magnitude of within-group variability across neurocognitive functioning in young people at Clinical High-Risk for psychosis (CHR-P) and comparison groups. Multistep, PRISMA/MOOSE-compliant systematic review (PROSPERO-CRD42020192826) of the Web of Science database, Cochrane Central Register of Reviews and Ovid/PsycINFO and trial registries up to July 1, 2020. The risk of bias was assessed using a modified version of the NOS for cohort and cross-sectional studies. Original studies reporting neurocognitive functioning in individuals at CHR-P compared to healthy controls (HC) or first-episode psychosis (FEP) patients were included. The primary outcome was the random-effect meta-analytic variability ratios (VR). Secondary outcomes included the coefficient of variation ratios (CVR). Seventy-eight studies were included, relating to 5162 CHR-P individuals, 2865 HC and 486 FEP. The CHR-P group demonstrated higher variability compared to HC (in descending order of magnitude) in visual memory (VR: 1.41, 95% CI 1.02-1.94), executive functioning (VR: 1.31, 95% CI 1.18-1.45), verbal learning (VR: 1.29, 95% CI 1.15-1.45), premorbid IQ (VR: 1.27, 95% CI 1.09-1.49), processing speed (VR: 1.26, 95% CI 1.07-1.48), visual learning (VR: 1.20, 95% CI 1.07-1.34), and reasoning and problem solving (VR: 1.17, 95% CI 1.03-1.34). In the CVR analyses the variability in CHR-P population remains in the previous neurocognitive domains and emerged in attention/vigilance, working memory, social cognition, and visuospatial ability. The CHR-P group transitioning to psychosis showed greater VR in executive functioning compared to those not developing psychosis and compared to FEP groups. Clinical high risk for psychosis subjects shows increased variability in neurocognitive performance compared to HC. The main limitation of this study is the validity of the VR and CVR as an index of variability which has received debate. This finding should be explored by further individual-participant data research and support precision medicine approaches.

Regulatory T cells enhance Th17 migration in psoriatic arthritis which is reversed by anti-TNF.

Regulatory T cells (Treg) prevent the migration of effector T cells toward sites of inflammation, thereby limiting disease progression. We investigated this aspect of Treg function using psoriatic arthritis (PsA) as an exemplar of chronic inflammation. Patients with PsA had an increased Th17:Treg ratio which was reversed by anti-tumor necrosis factor (TNF) therapy. Utilizing an in vitro migration assay, Treg from patients with PsA treated with conventional therapy paradoxically boosted CCR6+ effector T-cell (a surrogate for Th17) migration toward CCL20. In contrast, Treg from patients with PsA treated with anti-TNF suppressed CCL20-driven effector T-cell migration. The boosting effect of TNF blockade upon Treg suppression of migration was accompanied by increased effector T-cell CCL20 production and enhanced interaction between Treg and effector T cells. This study provides mechanistic insight into Treg modulation of effector T-cell migration in patients with chronic inflammation and how this can be targeted by therapy.

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). Design, Setting, and Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Main Outcomes and Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). Conclusions and Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

Corrigendum to "Real-world long-term outcomes in individuals at clinical risk for psychosis: The case for extending duration of care" [EClinicalMedicine 28 (2020) 100,578].

[This corrects the article DOI: 10.1016/j.eclinm.2020.100578.].

Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.

BACKGROUND: Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis. METHOD: The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia. RESULTS: A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model. CONCLUSIONS: Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.

Implementing Precision Psychiatry: A Systematic Review of Individualized Prediction Models for Clinical Practice.

BACKGROUND: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to estimate the individual risk of being affected with a condition (diagnostic), developing outcomes (prognostic), or responding to treatments (predictive) in mental disorders. METHODS: PRISMA/RIGHT/CHARMS-compliant systematic review of the Web of Science, Cochrane Central Register of Reviews, and Ovid/PsycINFO databases from inception until July 21, 2019 (PROSPERO CRD42019155713) to identify diagnostic/prognostic/predictive prediction studies that reported individualized estimates in psychiatry and that were internally or externally validated or implemented. Random effect meta-regression analyses addressed the impact of several factors on the accuracy of prediction models. FINDINGS: Literature search identified 584 prediction modeling studies, of which 89 were included. 10.4% of the total studies included prediction models internally validated (n = 61), 4.6% models externally validated (n = 27), and 0.2% (n = 1) models considered for implementation. Across validated prediction modeling studies (n = 88), 18.2% were diagnostic, 68.2% prognostic, and 13.6% predictive. The most frequently investigated condition was psychosis (36.4%), and the most frequently employed predictors clinical (69.5%). Unimodal compared to multimodal models (ß = .29, P = .03) and diagnostic compared to prognostic (ß = .84, p < .0001) and predictive (ß = .87, P = .002) models were associated with increased accuracy. INTERPRETATION: To date, several validated prediction models are available to support the diagnosis and prognosis of psychiatric conditions, in particular, psychosis, or to predict treatment response. Advancements of knowledge are limited by the lack of implementation research in real-world clinical practice. A new generation of implementation research is required to address this translational gap.

Annual Research Review: Prevention of psychosis in adolescents - systematic review and meta-analysis of advances in detection, prognosis and intervention.

BACKGROUND: The clinical high-risk state for psychosis (CHR-P) paradigm has facilitated the implementation of psychosis prevention into clinical practice; however, advancements in adolescent CHR-P populations are less established. METHODS: We performed a PRISMA/MOOSE-compliant systematic review of the Web of Science database, from inception until 7 October 2019, to identify original studies conducted in CHR-P children and adolescents (mean age <18 years). Findings were systematically appraised around core themes: detection, prognosis and intervention. We performed meta-analyses (employing Q statistics and I 2 test) regarding the proportion of CHR-P subgroups, the prevalence of baseline comorbid mental disorders, the risk of psychosis onset and the type of interventions received at baseline. Quality assessment and publication bias were also analysed. RESULTS: Eighty-seven articles were included (n = 4,667 CHR-P individuals). Quality of studies ranged from 3.5 to 8 (median 5.5) on a modified Newcastle-Ottawa scale. Detection: Individuals were aged 15.6 ± 1.2 years (51.5% males), mostly (83%) presenting with attenuated positive psychotic symptoms. CHR-P psychometric accuracy improved when caregivers served as additional informants. Comorbid mood (46.4%) and anxiety (31.4%) disorders were highly prevalent. Functioning and cognition were impaired. Neurobiological studies were inconclusive. PROGNOSIS: Risk for psychosis was 10.4% (95%CI: 5.8%-18.1%) at 6 months, 20% (95%CI: 15%-26%) at 12 months, 23% (95%CI: 18%-29%) at 24 months and 23.3% (95%CI: 17.3%-30.7%) at ≥36 months. INTERVENTIONS: There was not enough evidence to recommend one specific treatment (including cognitive behavioural therapy) over the others (including control conditions) to prevent the transition to psychosis in this population. Randomised controlled trials suggested that family interventions, cognitive remediation and fish oil supplementation may improve cognition, symptoms and functioning. At baseline, 30% of CHR-P adolescents were prescribed antipsychotics and 60% received psychotherapy. CONCLUSIONS: It is possible to detect and formulate a group-level prognosis in adolescents at risk for psychosis. Future interventional research is required.

Real-world implementation of precision psychiatry: Transdiagnostic risk calculator for the automatic detection of individuals at-risk of psychosis.

BACKGROUND: Risk estimation models integrated into Electronic Health Records (EHRs) can deliver innovative approaches in psychiatry, but clinicians' endorsement and their real-world usability are unknown. This study aimed to investigate the real-world feasibility of implementing an individualised, transdiagnostic risk calculator to automatically screen EHRs and detect individuals at-risk for psychosis. METHODS: Feasibility implementation study encompassing an in-vitro phase (March 2018 to May 2018) and in-vivo phase (May 2018 to April 2019). The in-vitro phase addressed implementation barriers and embedded the risk calculator (predictors: age, gender, ethnicity, index cluster diagnosis, age*gender) into the local EHR. The in-vivo phase investigated the real-world feasibility of screening individuals accessing secondary mental healthcare at the South London and Maudsley NHS Trust. The primary outcome was adherence of clinicians to automatic EHR screening, defined by the proportion of clinicians who responded to alerts from the risk calculator, over those contacted. RESULTS: In-vitro phase: implementation barriers were identified/overcome with clinician and service user engagement, and the calculator was successfully integrated into the local EHR through the CogStack platform. In-vivo phase: 3722 individuals were automatically screened and 115 were detected. Clinician adherence was 74% without outreach and 85% with outreach. One-third of clinicians responded to the first email (37.1%) or phone calls (33.7%). Among those detected, cumulative risk of developing psychosis was 12% at six-month follow-up. CONCLUSION: This is the first implementation study suggesting that combining precision psychiatry and EHR methods to improve detection of individuals with emerging psychosis is feasible. Future psychiatric implementation research is urgently needed.

Real-world long-term outcomes in individuals at clinical risk for psychosis: The case for extending duration of care.

BACKGROUND: Most services for individuals at Clinical High Risk for Psychosis (CHR-P) provide short-term clinical care. This study determines the real-world and long-term clinical outcomes beyond transition to psychosis in a large cohort of CHR-P individuals. METHOD: Retrospective RECORD-compliant real-world Electronic Health Records (EHR) cohort study in secondary mental health care (the South London and the Maudsley -SLaM- NHS Foundation Trust). All CHR-P patients accessing the CHR-P service at SLaM in the period 2001-2018 were included. Main outcomes were long-term cumulative risk of first: (i) developing an ICD-10 psychotic disorder (primary outcome), receiving a treatment with (iia) antipsychotic medication, (iib) benzodiazepines, (iic) other psychotropic medications, (iid) psychotherapy, receiving an (iiia) informal or (iiib) compulsory admission into a mental health hospital, and the time to these events; (iiic) number of days spent in hospital and (iv) cumulative risk of death for any reason and age/gender Standardised Mortality Ratio (SMR). Data were extracted from the EHR and analysed with Kaplan Meier failure functions, Cox and zero-inflated negative binomial regressions. FINDINGS: 600 CHR-P patients (80.43% Attenuated Psychotic Symptoms, APS; 18.06%, Brief and Limited Intermittent Psychotic Symptoms, BLIPS, 1.51% Genetic Risk and Deterioration Syndrome) were included (mean age 22.63 years, range 13-36; 55.33% males; 46.44% white, mean duration of untreated attenuated psychotic symptoms 676.32 days, 1105.40 SD). The cumulative risk to first psychosis was 0.365 (95%CI 0.302-0.437) at 11 years; first antipsychotic 0.777 (95%CI 0.702-0.844) at 9 years; first benzodiazepine 0.259 (95%CI 0.183-0.359) at 12 years; first other types of medications 0.630 (95%CI 0.538-0.772) at 9 years; first psychotherapy 0.814 (95%CI 0.764-0.859) at 9 years; first informal admission 0.378 (95%CI 0.249-0.546) at 12 years; first compulsory admission 0.251 (95%CI 0.175-0.352) at 12 years; those admitted spent on average 94.84 (SD=169.94) days in hospital; the cumulative risk of death for any reason was 0.036 (95%CI 0.012-0.103) at 9 years, with an SMR of 3.9 (95%CI 1.20-6.6). Compared to APS, BLIPS had a higher risk of developing psychosis, being admitted compulsorily into hospital, receiving antipsychotics and benzodiazepines and lower probability of receiving psychotherapy. Other prognostic factors of long-term outcomes included age, symptoms severity, duration of untreated attenuated psychotic symptoms, ethnicity and employment status. INTERPRETATION: Duration of care provided by CHR-P services should be expanded to address long-term real-world outcomes. FUNDING: This study was supported by the King's College London Confidence in Concept award from the Medical Research Council (MRC) (MC_PC_16048) to PF-P. GSP is supported by the Alicia Koplowitz Foundation. HB is supported by a National Institute for Health Research Maudsley Biomedical Research Centre studentship.

Antenatal risk factors for child maltreatment: Linkage of data from a birth cohort study to child welfare records.

BACKGROUND: Understanding the risk factors for child maltreatment is critical to efforts to reduce its prevalence. OBJECTIVE: This study investigated the association between characteristics and circumstances of mothers during pregnancy and the subsequent identification of concerns about child maltreatment. PARTICIPANTS AND SETTING: The study drew on two data sets: (i) data from questionnaires administered to the expectant mothers of 11,332 children born in a deprived multi-ethnic local authority in England between 2007 and 2011, for a birth cohort study, and (ii) administrative data on children referred to child welfare services. METHODS: The linkage of these two pre-existing data sets enabled the prospective study of risk factors for child maltreatment. RESULTS: A range of factors captured during the antenatal period were associated with an increased likelihood of subsequent recorded child maltreatment concerns, including: younger maternal age (HR=0.96; p < .001), lower maternal education level (HR=1.36; p < .001), maternal mental illness (HR=1.17; p = .001), maternal smoking in pregnancy (HR=1.69; p < .001), single motherhood (HR=1.41; p = .022), larger family size (HR=1.13; p < .001), multiple deprivation (HR=1.01; p = .011), social housing (HR=1.72; p < .001), paternal unemployment (HR=1.79; p < .001), and the receipt of means-tested welfare benefits (HR=1.43; p < .001). A greater total number of risk factors during pregnancy also increased the risk of subsequent maltreatment concerns (HR=1.45; p < .001). CONCLUSIONS: The identification of multiple risk factors in this study supports claims that single targeted interventions are unlikely to be successful in preventing or reducing child maltreatment due to its multifactorial nature, and that multidimensional interventions are required.

Advancing mental health equality: a mapping review of interventions, economic evaluations and barriers and facilitators.

BACKGROUND: This work aimed to identify studies of interventions seeking to address mental health inequalities, studies assessing the economic impact of such interventions and factors which act as barriers and those that can facilitate interventions to address inequalities in mental health care. METHODS: A systematic mapping method was chosen. Studies were included if they: (1) focused on a population with: (a) mental health disorders, (b) protected or other characteristics putting them at risk of experiencing mental health inequalities; (2) addressed an intervention focused on addressing mental health inequalities; and (3) met criteria for one or more of three research questions: (i) primary research studies (any study design) or systematic reviews reporting effectiveness findings for an intervention or interventions, (ii) studies reporting economic evaluation findings, (iii) primary research studies (any study design) or systematic reviews identifying or describing, potential barriers or facilitators to interventions. A bibliographic search of MEDLINE, HMIC, ASSIA, Social Policy & Practice, Sociological Abstracts, Social Services Abstracts and PsycINFO spanned January 2008 to December 2018. Study selection was performed according to inclusion criteria. Data were extracted and tabulated to map studies and summarise published research on mental health inequalities. A visual representation of the mapping review (a mapping diagram) is included. RESULTS: Overall, 128 studies met inclusion criteria: 115 primary studies and 13 systematic reviews. Of those, 94 looked at interventions, 6 at cost-effectiveness and 36 at barriers and facilitators. An existing taxonomy of disparities interventions was used and modified to categorise interventions by type and strategy. Most of the identified interventions focused on addressing socioeconomic factors, race disparities and age-related issues. The most frequently used intervention strategy was providing psychological support. Barriers and associated facilitators were categorised into groups including (not limited to) access to care, communication issues and financial constraints. CONCLUSIONS: The mapping review was useful in assessing the spread of literature and identifying highly researched areas versus prominent gaps. The findings are useful for clinicians, commissioners and service providers seeking to understand strategies to support the advancement of mental health equality for different populations and could be used to inform further research and support local decision-making. SYSTEMATIC REVIEW REGISTRATION: Not applicable.

World/self ambivalence: A shared mechanism in different subsets of psychotic experiences? Linking symptoms with resting-state fMRI.

The psychosis spectrum comprises heterogeneous disorders characterized by both world-related and self-related symptoms. How these symptoms may arise with similar features in spite of the different aetiologies is yet an unsolved question. In behavior narrative review, we compare three conditions characterized by psychotic experiences (schizophrenia, substance-use disorder and sensory-deprivation) searching for links between their phenomenological features and the mechanisms underlying their onset. Clinically, psychotic experiences are characterized by the reciprocal contamination of world- and self-related contents, termed 'world/self ambivalence'. Neuroimaging evidence suggests that the imbalance between stimuli-, self-, and attention-related functional networks (visual/auditory, default-mode, and salience network respectively) assumes central relevance in all the conditions considered. Phenomenology and neurobiology were thus interrelated in light of the reviewed literature, identifying two key neuronal mechanisms which may lead to world/self ambivalence. First, psychotic experiences are associated with the relative dominance of one network over the other (default-mode over auditory/visual networks, or vice-versa), prompting an excess of internal or external pressure to the experienced ambivalence between world and self. Second, an altered salience network resting-state functional connectivity could generate a dysregulation of the attentive fluctuations from self- to world-related activity, thus blurring the boundary between the environment and oneself, labelled the 'world/self boundary'.

Real-world evidence in Alzheimer's disease: The ROADMAP Data Cube.

INTRODUCTION: The ROADMAP project aimed to provide an integrated overview of European real-world data on Alzheimer's disease (AD) across the disease spectrum. METHODS: Metadata were identified from data sources in catalogs of European AD projects. Priority outcomes for different stakeholders were identified through systematic literature review, patient and public consultations, and stakeholder surveys. RESULTS: Information about 66 data sources and 13 outcome domains were integrated into a Data Cube. Gap analysis identified cognitive ability, functional ability/independence, behavioral/neuropsychiatric symptoms, treatment, comorbidities, and mortality as the outcomes collected most. Data were most lacking in caregiver-related outcomes. In general, electronic health records covered a broader, less detailed data spectrum than research cohorts. DISCUSSION: This integrated real-world AD data overview provides an intuitive visual model that facilitates initial assessment and identification of gaps in relevant outcomes data to inform future prospective data collection and matching of data sources and outcomes against research protocols.