Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists.

INTRODUCTION: At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap. METHODS AND ANALYSIS: This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56-80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences-Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery. ETHICS AND DISSEMINATION: The study received the following approvals: South Central-Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN93895792.

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement.

BACKGROUND: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. METHOD: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14-35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. DISCUSSION: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. TRIAL REGISTRATION: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Autism Spectrum Disorder in Early Intervention in Psychosis Services: Implementation and Findings of a 3-step Screening and Diagnostic Protocol.

Evidence indicates that autism spectrum disorder (ASD) is underidentified in populations with psychosis, but that clinical presentations of comorbid ASD and psychosis (ASD-P) and specific treatment needs that may relate to this group are not well understood. In fact, recent studies of ASD in first-episode psychosis suggest that there may be a specific clinical presentation of ASD-P. In response, the Cambridgeshire and Peterborough Early Intervention in Psychosis (EIP) service in the UK implemented and evaluated a 3-step ASD screening and diagnostic protocol, using the Autism Spectrum Disorder in Adults Screening Questionnaire (ASDASQ), case note review, and the Autism Diagnostic Observation Schedule (ADOS-2) and the Childhood Autism Spectrum Test (CAST). As a quality improvement project, the evaluation aimed to (1) establish the prevalence of patients with ASD-P, (2) describe characteristics of the clinical presentation of ASD-P and compare them to those of patients suffering from psychosis but no ASD, and (3) determine any differences in treatment between psychosis patients with and without ASD. Notably, at least 9% of the EIP service caseload met the criteria for a diagnosis of ASD-P, with half identified via the implementation of this protocol. The patients with ASD-P had specific clinical presentations and treatment needs that differed from those of patients with psychosis but no ASD. Thus, the findings from this study supported existing evidence concerning the underdetection of ASD in EIP populations. Our findings also added to emerging evidence for a clinical presentation of ASD-P with specific treatment needs. Our protocol has now been established as routine practice, and its implementation has improved the detection and treatment of patients with ASD-P within our EIP service.

Using histology to evaluate micro-CT findings of trauma in three post-mortem samples - First steps towards method validation.

Forensic imaging technology has rapidly advanced over the past several decades and is gaining increasing significance in medico-legal death investigations. Medical-grade computed tomography (CT) is now routinely used in post-mortem examinations at numerous institutions across the globe. However, the resolution of medical-grade CT is limited and unsuitable when used to depict some smaller anatomical structures or micro-trauma. High-resolution micro-CT offers up to 100× the resolution to overcome this problem but is a very recent addition to the field of forensic radiology. Few studies so far have attempted to validate the results which is an essential prerequisite for it to be used in the criminal justice process as demanded by regulatory bodies. This study directly compares micro-CT images with histology, the current gold standard. Three cases were examined: two larynges from suspected strangulations and one ribcage of a case of fatal child abuse. A strong correlation was observed between histology and micro-CT as the majority of skeletal injuries were identified correctly. This paper discusses the forensic implications of the results and how micro-CT is complementary to histology.

Clinically significant personality traits in individuals at high risk of developing psychosis.

It is still unclear to what extent personality may influence the development of psychosis. We aimed to explore significant personality traits in individuals at high-risk (HR) for psychosis. Personalities of forty HR individuals and a matched sample of 40 healthy volunteers (HVs) were evaluated with the Millon Multiaxial Inventory (MCMI-III). They were also assessed with the Positive and Negative Symptoms Scale (PANSS), Beck Depression and Anxiety Inventories (BDI-II and BAI), Global Assessment of Functioning (GAF) and Mini-International Neuropsychiatric Interview (MINI 6.0.0). Fisher's exact test was employed to compare frequency of traits. Mann-Whitney U test and logistic regression were used to establish relationships between traits and symptoms, and the effect of age, sex and symptoms on such traits. Most HR individuals (97.5%) had at least one significant trait; 75% had personality disorders, mainly depressive, borderline or schizotypal. Only histrionic and narcissistic traits were more prevalent in HVs. Negative symptoms were related to schizoid and paranoid traits. Depression was more severe with borderline traits. Most HR individuals (67.6%) had more than one DSM-IV Axis I diagnosis, mainly depressive/anxiety disorders. Transition rate was low (5%). Certain personality profiles may not be markers for conversions to psychosis but contribute to high morbidity in HR individuals.

Attachment styles and clinical correlates in people at ultra high risk for psychosis.

Evidence suggests that attachment styles may influence subclinical psychosis phenotypes (schizotypy) and affective disorders and may play a part in the association between psychosis and childhood adversity. However, the role of attachment in the initial stages of psychosis remains poorly understood. Our main aim was to describe and compare attachment styles in 60 individuals at ultra high risk for psychosis (UHR) and a matched sample of 60 healthy volunteers (HV). The HV had lower anxious and avoidant attachment scores than the UHR individuals (p < .001). Sixty-nine percentage of the UHR group had more than one DSM-IV diagnosis, mainly affective and anxiety disorders. The UHR group experienced more trauma (p < .001) and more mood and anxiety symptoms (p < .001). Interestingly, in our UHR group, only schizotypy paranoia was correlated with insecure attachment. In the HV group, depression, anxiety, schizotypy paranoia, and social anxiety were correlated with insecure attachment. This difference and some discrepancies with previous studies involving UHR suggest that individuals at UHR may compose a heterogeneous group; some experience significant mood and/or anxiety symptoms that may not be explained by specific attachment styles. Nonetheless, measuring attachment in UHR individuals could help maximize therapeutic relationships to enhance recovery.

Use of the Theory of Planned Behaviour to assess factors influencing the identification of students at clinical high-risk for psychosis in 16+ Education.

BACKGROUND: The longer psychotic disorders are untreated the worse their prognosis. Increasing the awareness of early psychosis by professionals who come into regular contact with young people is one strategy that could reduce treatment delay. As teachers engage with students on a daily basis, their role could be exploited to increase awareness of the early signs of psychosis. This study employed the Theory of Planned Behaviour (TPB) to identify and measure factors that influence identification of students at high-risk (HR) of developing psychosis in 16+ educational institutions. METHODS: An elicitation phase revealed beliefs underlying teachers' motivations to detect HR students and informed the construction of a preliminary 114-item questionnaire incorporating all constructs outlined in the TPB. To define the determinants of teachers' intention to identify HR students, 75 teachers from secondary and further education institutions in 12 counties surrounding Cambridgeshire completed the questionnaire. A psychometric model of item response theory was used to identify redundant items and produce a reduced questionnaire that would be acceptable to teachers. RESULTS: The final instrument comprised 73 items and showed acceptable reliability (α = 0.69-0.81) for all direct measures. Teacher's confidence and control over identification of HR students was low. Although identification of HR students was considered worthwhile, teachers believed that their peers, students and particularly their managers might not approve. Path analysis revealed that direct measures of attitude and PBC significantly predicted intention, but subjective norm did not. PBC was the strongest predictor of intention. Collectively, the direct measures explained 37 % of the variance of intention to identify HR for psychosis. CONCLUSIONS: This research demonstrated how the TPB can be used to identify and measure factors that influence identification of students at HR of developing psychosis in 16+ educational institutions and confirmed the feasibility, reliability and acceptability of a TPB-based questionnaire for teachers. Consideration of the key determinants of identification in schools will facilitate the design of successful educational intervention strategies with the potential to reduce treatment delays for HR students.

Clinical effectiveness and cost-effectiveness of tailored intensive liaison between primary and secondary care to identify individuals at risk of a first psychotic illness (the LEGs study): a cluster-randomised controlled trial.

BACKGROUND: General practitioners are usually the first health professionals to be contacted by people with early signs of psychosis. We aimed to assess whether increased liaison between primary and secondary care improves the clinical effectiveness and cost-effectiveness of detection of people with, or at high risk of developing, a first psychotic illness. METHODS: Our Liaison and Education in General Practices (LEGs) study was a cluster-randomised controlled trial of primary care practices (clusters) in Cambridgeshire and Peterborough, UK. Consenting practices were randomly allocated (1:1) to a 2 year low-intensity intervention (a postal campaign, consisting of biannual guidelines to help identify and refer individuals with early signs of psychosis) or a high-intensity intervention, which additionally included a specialist mental health professional who liaised with every practice and a theory-based educational package. Practices were not masked to group allocation. Practices that did not consent to be randomly assigned comprised a practice-as-usual (PAU) group. The primary outcome was number of referrals of patients at high risk of developing psychosis to the early intervention service per practice site. New referrals were assessed clinically and stratified into those who met criteria for high risk or first-episode psychotic illness (FEP; together: psychosis true positives), and those who did not fulfil such criteria for psychosis (false positives). Referrals from PAU practices were also analysed. We assessed cost-effectiveness with decision analytic modelling in terms of the incremental cost per additional true positive identified. The trial is registered at the ISRCTN registry, number ISRCTN70185866. FINDINGS: Between Dec 22, 2009, and Sept 7, 2010, 54 of 104 eligible practices provided consent and between Feb 16, 2010, and Feb 11, 2011, these practices were randomly allocated to interventions (28 to low intensity and 26 to high intensity); the remaining 50 practices comprised the PAU group. Two high-intensity practices were excluded from the analysis. In the 2 year intervention period, high-intensity practices referred more FEP cases than did low-intensity practices (mean 1.25 [SD 1.2] for high intensity vs 0.7 [0.9] for low intensity; incidence rate ratio [IRR] 1.9, 95% CI 1.05-3.4, p=0.04), although the difference was not statistically significant for individuals at high risk of psychosis (0.9 [1.0] vs 0.5 [1.0]; 2.2, 0.9-5.1, p=0.08). For high risk and FEP combined, high-intensity practices referred both more true-positive (2.2 [1.7] vs 1.1 [1.7]; 2.0, 1.1-3.6, p=0.02) and false-positive (2.3 [2.4] vs 0.9 [1.2]; 2.6, 1.3-5.0, p=0.005) cases. Referral patterns did not differ between low-intensity and PAU practices. Total cost per true-positive referral in the 2 year follow-up was £26,785 in high-intensity practices, £27,840 in low-intensity practices, and £30,007 in PAU practices. INTERPRETATION: This intensive intervention to improve liaison between primary and secondary care for people with early signs of psychosis was clinically and cost effective. FUNDING: UK National Institute for Health Research.

Substance use in people at clinical high-risk for psychosis.

BACKGROUND: Some high-risk (HR) mental states for psychosis may lack diagnostic specificity and predictive value. Furthermore, psychotic-like experiences found in young populations may act not only as markers for psychosis but also for other non-psychotic psychiatric disorders. A neglected consideration in these populations is the effect of substance misuse and its role in the development of such mental states or its influence in the evolution toward full psychotic presentations. Therefore, the main aim of this study was to thoroughly describe past and current substance use profiles of HR individuals by comparing a consecutive cohort of young people at high risk referred to a population-based early intervention clinical service with a random sample of healthy volunteers (HV) recruited from the same geographical area. METHODS: We compared alcohol and substance use profiles of sixty help-seeking HR individuals and 60 healthy volunteers (HV). In addition to identification of abuse/dependence and influence on psychotic-like experiences, differences between HR individuals and HV were assessed for gender, ethnicity, occupational status, age of lifetime first substance use, prevalence and frequency of substance use. RESULTS: There were no cases of substance use disorder or dependence in either groups. HR individuals were significantly younger than HV when they first started to use substances (p = 0.014). The prevalence of overall HR substance use was similar to that of HV. Although HR individuals reported less cannabinoid use than HV currently (15% vs. 27%), and more in the past (40% vs. 30%), the differences were not statistically significant (p = 0.177 & 0.339 respectively). Current frequency of use was significantly higher for HR individuals than HV for alcohol (p = 0.001) and cannabinoids (p = 0.03). In this sample, only 5% of HR individuals converted to psychosis over a two-year follow-up. CONCLUSIONS: Certain profiles of substance use could potentially play a significant part in the evolution of HR presentations. Therefore, substance use may well represent a clinical domain that requires further emphasis and more detailed consideration in future studies.

Trauma history characteristics associated with mental states at clinical high risk for psychosis.

Traumatic experiences have been positively associated with both severity of attenuated psychotic symptoms in individuals at high risk (HR) for psychosis and transitions into psychotic disorders. Our aim was to determine what characteristics of the trauma history are more likely to be associated with individuals at HR. The Trauma History Screen (THS) was used to enable emphasis on number and perceived intensity of adverse life events and age at trauma exposure. Sixty help-seeking individuals who met HR criteria were compared to a random sample of 60 healthy volunteers. Both groups were aged 16-35 and resided in the same geographical location. HR participants experienced their first trauma at an earlier age, continued to experience trauma at younger developmental stages, especially during early/mid adolescence and were exposed to a high number of traumas. They were more depressed and anxious, but did not experience more distress in relation to trauma. Both incidences of trauma and age at which trauma occurred were the most likely predictors of becoming HR. This work emphasises the importance of assessing trauma characteristics in HR individuals to enable differentiation between psychotic-like experiences that may reflect dissociative responses to trauma and genuine prodromal psychotic presentations.

Comparison of high and low intensity contact between secondary and primary care to detect people at ultra-high risk for psychosis: study protocol for a theory-based, cluster randomized controlled trial.

BACKGROUND: The early detection and referral to specialized services of young people at ultra-high risk (UHR) for psychosis may reduce the duration of untreated psychosis and, therefore, improve prognosis. General practitioners (GPs) are usually the healthcare professionals contacted first on the help-seeking pathway of these individuals. METHODS/DESIGN: This is a cluster randomized controlled trial (cRCT) of primary care practices in Cambridgeshire and Peterborough, UK. Practices are randomly allocated into two groups in order to establish which is the most effective and cost-effective way to identify people at UHR for psychosis. One group will receive postal information about the local early intervention in psychosis service, including how to identify young people who may be in the early stages of a psychotic illness. The second group will receive the same information plus an additional, ongoing theory-based educational intervention with dedicated liaison practitioners to train clinical staff at each site. The primary outcome of this trial is count data over a 2-year period: the yield - number of UHR for psychosis referrals to a specialist early intervention in psychosis service - per primary care practice. DISCUSSION: There is little guidance on the essential components of effective and cost-effective educational interventions in primary mental health care. Furthermore, no study has demonstrated an effect of a theory-based intervention to help GPs identify young people at UHR for psychosis. This study protocol is underpinned by a robust scientific rationale that intends to address these limitations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70185866.

Psychiatric morbidity, functioning and quality of life in young people at clinical high risk for psychosis.

OBJECTIVE: Recent studies suggest that psychotic-like experiences may also act as markers for non-psychotic psychiatric disorders, which may indicate that the focus of research in individuals at high risk (HR) for psychosis needs updating. In this study we thoroughly examined the clinical and functional characteristics of a consecutive cohort of young people at HR for psychosis and compared them to a matched sample of healthy volunteers. METHOD: Between February 2010 and September 2012 60 help-seeking HR individuals, aged 16-35, were recruited from CAMEO Early Intervention in Psychosis Service, Cambridgeshire, UK. Forty-five age- and gender-matched healthy volunteers were randomly recruited from the same geographical area. Sociodemographic, psychiatric morbidity, functioning and quality of life measures were compared between both groups. RESULTS: HR individuals suffered a wide range of DSM-IV psychiatric disorders, mainly within the affective and anxiety diagnostic spectra. In comparison to healthy volunteers, young people at HR reported more suicidal ideation/intention, depressive and anxiety symptoms and presented with remarkably poor functioning and quality of life. CONCLUSION: The presence of co-morbid moderate or severe depressive and anxiety symptoms was common in our sample of young people at enhanced risk for psychosis. A HR mental state may be associated not only with an increased risk for psychosis, but also other psychiatric disorders. Our findings may have implications for the future implementation of therapeutic interventions that this population could benefit from.