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Cover of Understanding causes of and developing effective interventions for schizophrenia and other psychoses

Understanding causes of and developing effective interventions for schizophrenia and other psychoses

Programme Grants for Applied Research, No. 4.2

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Southampton (UK): NIHR Journals Library; .


This study developed our understanding of the social epidemiology of psychosis, which will help people at high risk of developing first-episode psychosis receive appropriate services focused on their current mental state. This programme, while working innovatively with general practitioners and sixth-form colleges, developed our understanding of the social epidemiology of psychosis. This will help people at high risk of developing psychosis receive appropriate services by focusing on their current mental state.



Early-intervention services (EISs) offer prompt and effective care to individuals with first-episode psychosis (FEP) and detect people at high risk (HR) of developing it.


We aimed to educate general practitioners about psychosis and guide their referrals to specialist care; investigate determinants of the transition of HR to FEP; and predict numbers of new cases to guide policy and service planning.

Incidence of psychosis in socially and ethnically diverse settings:

We studied the incidence of new referrals for psychosis in a well-established EIS called CAMEO [see www.cameo.nhs.uk (accessed 18 January 2016)] and built on other epidemiological studies. The overall incidence of FEP was 45.1 per 100,000 person-years [95% confidence interval (CI) 40.8 to 49.9 per 100,000 person-years]. This was two to three times higher than the incidence predicated by the UK Department of Health. We found considerable psychosis morbidity in diverse, rural communities.

Development of a population-level prediction tool for the incidence of FEP:

We developed and validated a population-level prediction tool, PsyMaptic, capable of accurately estimating the expected incidence of psychosis [see www.psymaptic.org/ (accessed 18 January 2016)].

The Liaison with Education and General practiceS (LEGS) trial to detect HR:

We tested a theory-based intervention to improve detection and referral of HR individuals in a cluster randomised controlled trial involving primary care practices in Cambridgeshire and Peterborough. Consenting practices were randomly allocated to (1) low-intensity liaison with secondary care, a postal campaign to help with the identification and referral of individuals with early signs of psychosis, or (2) the high-intensity theory-based intervention, which, in addition to the postal campaign, included a specialist mental health professional to liaise with each practice. Practices that did not consent to be randomised included a practice-as-usual (PAU) group. The approaches were implemented over 2 years for each practice between April 2010 and October 2013. New referrals were stratified into those who met criteria for HR/FEP (together: psychosis true positives) and those who did not fulfil such criteria (false positives). The primary outcome was the number of HR referrals per practice. Referrals from PAU practices were also analysed. We quantified the cost-effectiveness of the interventions and PAU using the incremental cost per additional true positive identified. Of 104 eligible practices, 54 consented to be randomised. Twenty-eight practices were randomised to low-intensity liaison and 26 practices were randomised to the high-intensity intervention. Two high-intensity practices withdrew. High-intensity practices referred more HR [incidence rate ratio (IRR) 2.2, 95% CI 0.9 to 5.1; p = 0.08], FEP (IRR 1.9, 95% CI 1.05 to 3.4; p = 0.04) and true-positive (IRR 2.0, 95% CI 1.1 to 3.6; p = 0.02) cases. High-intensity practices also referred more false-positive cases (IRR 2.6, 95% CI 1.3 to 5.0; p = 0.005); most (68%) of these were referred on to appropriate services. The total costs per true-positive referral in high-intensity practices were lower than those in low-intensity or PAU practices. Increasing the resources aimed at managing the primary–secondary care interface provided clinical and economic value.

The Prospective Analysis of At-risk mental states and Transitions into psycHosis (PAATH) study:

We aimed to identify the proportion of individuals at HR who make the transition into FEP and to elucidate the common characteristics that can help identify them. Sixty help-seeking HR individuals aged 16–35 years were stratified into those who met the criteria for HR/FEP (true positives) according to the Comprehensive Assessment of At-Risk Mental States (CAARMS) and those who did not (false positives). HR participants were followed up over 2 years using a comprehensive interview schedule. A random sample of 60 healthy volunteers (HVs) matched for age (16–35 years), sex and geographical area underwent the same battery of questionnaires. Only 5% of our HR sample transitioned to a structured clinical diagnosis of psychosis over 2 years. HR individuals had a higher prevalence of moderate or severe depression, anxiety and suicidality than HVs. In fact, psychometric analyses in other population samples indicate that psychotic experiences measure the severe end of a common mental distress factor, consistent with these results. HR individuals also experienced significantly more traumatic events than HVs, but equivalent distress. Almost half of HR individuals had at least one Schneiderian first-rank symptom traditionally considered indicative of schizophrenia and 21.6% had more than one. HR individuals had very poor global functioning and low quality of life.


This National Institute for Health Research programme developed our understanding of the social epidemiology of psychosis. A new theory-based intervention doubled the identification of HR and FEP in primary care and was cost-effective. The HR mental state has much in common with depression and anxiety; very few people transitioned to full psychosis over 2 years, in line with other recent evidence. This new understanding will help people at HR receive appropriate services focused on their current mental state.

Trial registration:

The primary LEGS trial is registered as ISRCTN70185866 and UKCRN ID 7036. The PAATH study is registered as UKCRN ID 7798.


The National Institute for Health Research Programme Grants for Applied Research programme.


Article history

The research reported in this issue of the journal was funded by PGfAR as project number RP-PG-0606-1335. The contractual start date was in August 2007. The final report began editorial review in April 2015 and was accepted for publication in December 2015. As the funder, the PGfAR programme agreed the research questions and study designs in advance with the investigators. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The PGfAR editors and production house have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.

Declared competing interests of authors


Copyright © Queen’s Printer and Controller of HMSO 2016. This work was produced by Perez et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

Included under terms of UK Non-commercial Government License.

Bookshelf ID: NBK350254PMID: 27010053DOI: 10.3310/pgfar04020


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