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The unpredictability and uncertainty of the COVID-19 pandemic; the associated lockdowns, physical distancing, and other containment strategies; and the resulting economic breakdown could increase the risk of mental health problems and exacerbate health inequalities. Preliminary findings suggest adverse mental health effects in previously healthy people and especially in people with pre-existing mental health disorders. Despite the heterogeneity of worldwide health systems, efforts have been made to adapt the delivery of mental health care to the demands of COVID-19. Mental health concerns have been addressed via the public mental health response and by adapting mental health services, mostly focusing on infection control, modifying access to diagnosis and treatment, ensuring continuity of care for mental health service users, and paying attention to new cases of mental ill health and populations at high risk of mental health problems. Sustainable adaptations of delivery systems for mental health care should be developed by experts, clinicians, and service users, and should be specifically designed to mitigate disparities in health-care provision. Thorough and continuous assessment of health and service-use outcomes in mental health clinical practice will be crucial for defining which practices should be further developed and which discontinued. For this Position Paper, an international group of clinicians, mental health experts, and users of mental health services has come together to reflect on the challenges for mental health that COVID-19 poses. The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery. Thus, the COVID-19 pandemic could be an opportunity to improve mental health services., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Delayed treatment for first episodes of psychosis predicts worse outcomes. We hypothesised that delaying treatment makes all symptoms more refractory, with harm worsening first quickly, then more slowly. We also hypothesised that although delay impairs treatment response, worse symptoms hasten treatment, which at presentation mitigates the detrimental effect of treatment delay on symptoms., Methods: In this longitudinal analysis and modelling study, we included two longitudinal cohorts of patients with first-episode psychosis presenting to English early intervention services from defined catchments: NEDEN (recruiting 1003 patients aged 14-35 years from 14 services between Aug 1, 2005, and April 1, 2009) and Outlook (recruiting 399 patients aged 16-35 years from 11 services between April 1, 2006, and Feb 28, 2009). Patients were assessed at baseline, 6 months, and 12 months with the Positive and Negative Symptom Scale (PANSS), Calgary Depression Scale for Schizophrenia, Mania Rating Scale, Insight Scale, and Social and Occupational Functioning Assessment Scale. Regression was used to compare different models of the relationship between duration of untreated psychosis (DUP) and total symptoms at 6 months. Growth curve models of symptom subscales tested predictions arising from our hypotheses., Findings: We included 948 patients from the NEDEN study and 332 patients from the Outlook study who completed baseline assessments and were prescribed dopamine antagonist antipsychotics. For both cohorts, the best-fitting models were logarithmic, describing a curvilinear relationship of DUP to symptom severity: longer DUP predicted reduced treatment response, but response worsened more slowly as DUP lengthened. Increasing DUP by ten times predicted reduced improvement in total symptoms (ie, PANSS total) by 7·339 (95% CI 5·762 to 8·916; p<0·0001) in NEDEN data and 3·846 (1·689 to 6·003; p=0·0005) in Outlook data. This was true of treatment response for all symptom types. Nevertheless, longer DUP was not associated with worse presentation for any symptoms except depression in NEDEN (coefficients 0·099 [95% CI 0·033 to 0·164]; p=0·0028 in NEDEN and 0·007 [-0·081 to 0·095]; p=0·88 in Outlook)., Interpretation: Long DUP was associated with reduced treatment response across subscales, consistent with a harmful process upstream of individual symptoms' mechanisms; response appeared to worsen quickly at first, then more slowly. These associations underscore the importance of rapid access to a comprehensive range of treatments, especially in the first weeks after psychosis onset., Funding: UK Department of Health, National Institute of Health Research, and Medical Research Council., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4·0 license. Published by Elsevier Ltd.. All rights reserved.)

As part of the Roamer project, we sought to have a picture of the available mental health research (MHR) funding, capacity-building and infrastructures resources and to establish consensus-based recommendations that would allow an increase of European MHR resources and enable better use and accessibility to them. The methods fell into three sections (i) a review of the literature, (ii) a mental health-related keywords search within the Cordis ® , On-Course ® and Meril ® databases which contain information on European research funding, training and infrastructures. These reviews provided an overview that was presented to (iii) two experts workshops with 28 participants drawn from academic which identified gaps and produced recommendations. The literature review illustrates the debates in the scientific community on funding, training and infrastructures. The database searches estimated the fraction of health research resources available for mental health. Eight overarching goals for MHR resources were identified by the workshops; each of them was carried out with several practical recommendations. Resources for MHR are scarce considering the burden of mental disorders, the high rate of return of MHR and the under-investment of the field. The recommendations are urgently warranted to increase resources and their optimal access and use., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

As part of the Roamer project, we aimed at revealing the share of health research budgets dedicated to mental health, as well as on the amounts allocated to such research for four European countries. Finland, France, Spain and the United Kingdom national public and non-profit funding allocated to mental health research in 2011 were investigated using, when possible, bottom-up approaches. Specifics of the data collection varied from country to country. The total amount of public and private not for profit mental health research funding for Finland, France, Spain and the UK was €10·2, €84·8, €16·8, and €127·6 million, respectively. Charities accounted for a quarter of the funding in the UK and less than six per cent elsewhere. The share of health research dedicated to mental health ranged from 4·0% in the UK to 9·7% in Finland. When compared to the DALY attributable to mental disorders, Spain, France, Finland, and the UK invested respectively €12·5, €31·2, €39·5, and €48·7 per DALY. Among these European countries, there is an important gap between the level of mental health research funding and the economic and epidemiologic burden of mental disorders., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Background: Patient Reported Outcome Measures (PROMs) assess health status and health-related quality of life from the patient/service user perspective. Our study aimed to: i. develop a PROM for recovery from drug and alcohol dependence that has good face and content validity, acceptability and usability for people in recovery; ii. evaluate the psychometric properties and factorial structure of the new PROM ('SURE')., Methods: Item development included Delphi groups, focus groups, and service user feedback on draft versions of the new measure. A 30-item beta version was completed by 575 service users (461 in person [IP] and 114 online [OL]). Analyses comprised rating scale evaluation, assessment of psychometric properties, factorial structure, and differential item functioning., Results: The beta measure had good face and content validity. Nine items were removed due to low stability, low factor loading, low construct validity or high complexity. The remaining 21 items were re-scaled (Rasch model analyses). Exploratory and confirmatory factor analyses revealed 5 factors: substance use, material resources, outlook on life, self-care, and relationships. The MIMIC model indicated 95% metric invariance across the IP and OL samples, and 100% metric invariance for gender. Internal consistency and test-retest reliability were granted. The 5 factors correlated positively with the corresponding WHOQOL-BREF and ARC subscales and score differences between participant sub-groups confirmed discriminative validity., Conclusion: 'SURE' is a psychometrically valid, quick and easy-to-complete outcome measure, developed with unprecedented input from people in recovery. It can be used alongside, or instead of, existing outcome tools., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Objectives: Acceptance and Commitment Therapy (ACT) is a contextual cognitive-behavioural approach with a developing evidence base for clinical and cost-effectiveness as an individually-delivered intervention to promote recovery from psychosis. ACT also lends itself to brief group delivery, potentially increasing access to therapy without inflating costs. This study examined, for the first time, the feasibility and acceptability of ACT groups for people with psychosis (G-ACTp)., Methods: Participants were recruited from community psychosis teams. Ratings of user satisfaction, and pre-post change in self-rated functioning (primary outcome), mood (secondary outcome) and ACT processes were all completed with an independent assessor. Of 89 people recruited, 83 completed pre measures, 69 started the four-week G-ACTp intervention, and 65 completed post measures., Results: Independently assessed acceptability and satisfaction were high. Functioning (Coeff. = -2.4, z = -2.9, p = 0.004; 95% CI: -4.0 to -0.8; within subject effect size (ES) d = 0.4) and mood (Coeff. = -2.3, z = -3.5, p = 0.001; 95% CI: -3.5 to -1.0; d = 0.4) improved from baseline to follow-up. Commensurate changes in targeted ACT processes were consistent with the underlying model., Limitations: The uncontrolled, pre-post design precluded blinded assessments, and may have inflated effect sizes. Participants may have improved as a result of other factors, and findings require replication in a randomized controlled trial (RCT)., Conclusions: This preliminary study showed that brief group ACT interventions for people with psychosis are feasible and acceptable. Uncontrolled, pre-post assessments suggest small clinical improvements, and changes in psychological processes consistent with an ACT model. Replication in an RCT is required, before implementation can be recommended., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Mental and brain disorders represent the greatest health burden to Europe-not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society. Here, we describe a comprehensive, coordinated mental health research agenda for Europe and worldwide. This agenda was based on systematic reviews of published work and consensus decision making by multidisciplinary scientific experts and affected stakeholders (more than 1000 in total): individuals with mental health problems and their families, health-care workers, policy makers, and funders. We generated six priorities that will, over the next 5-10 years, help to close the biggest gaps in mental health research in Europe, and in turn overcome the substantial challenges caused by mental disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Several efforts to develop pharmacological treatments with a beneficial effect on cognition in schizophrenia are underway, while cognitive remediation has shown modest effects on cognitive performance. Our goal was to test if pharmacological augmentation of cognitive training would result in enhancement of training-induced learning. We chose modafinil as the pharmacological augmenting agent, as it is known to have beneficial effects on learning and cognition. 49 participants with chronic schizophrenia were enroled in a double-blind, placebo-controlled study across two sites and were randomised to either modafinil (200mg/day) or placebo. All participants engaged in a cognitive training program for 10 consecutive weekdays. The primary outcome measure was the performance on the trained tasks and secondary outcome measures included MATRICS cognitive battery, proxy measures of everyday functioning and symptom measures. 84% of the participants completed all study visits. Both groups showed significant improvement in the performance of the trained tasks suggesting potential for further learning. Modafinil did not induce differential enhancement on the performance of the trained tasks or any differential enhancement of the neuropsychological and functional measures compared to placebo. Modafinil showed no significant effects on symptom severity. Our study demonstrated that combining pharmacological compounds with cognitive training is acceptable to patients and can be implemented in large double-blind randomised controlled trials. The lack of differential enhancement of training-induced learning raises questions, such as choice and optimal dose of drug, cognitive domains to be trained, type of cognitive training, intervention duration and chronicity of illness that require systematic investigation in future studies., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

Background: Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer's motivation to comply., Methods: In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114., Findings: 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23-0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40-1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33-0·98, p=0·042)., Interpretation: This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and compliance., Funding: UK Medical Research Council and the National Institute for Health Research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Improving cognition in people with neuropsychiatric disorders remains a major clinical target. By themselves pharmacological and non-pharmacological approaches have shown only modest effects in improving cognition. In the present study we tested a recently-proposed methodology to combine CT with a 'cognitive-enhancing' drug to improve cognitive test scores and expanded on previous approaches by delivering combination drug and CT, over a long intervention of repeated sessions, and used multiple tasks to reveal the cognitive processes being enhanced. We also aimed to determine whether gains from this combination approach generalised to untrained tests. In this proof of principle randomised-controlled trial thirty-three healthy volunteers were randomised to receive either modafinil or placebo combined with daily cognitive training over two weeks. Volunteers were trained on tasks of new-language learning, working memory and verbal learning following 200 mg modafinil or placebo for ten days. Improvements in trained and untrained tasks were measured. Rate of new-language learning was significantly enhanced with modafinil, and effects were greatest over the first five sessions. Modafinil improved within-day learning rather than between-day retention. No enhancement of gains with modafinil was observed in working memory nor rate of verbal learning. Gains in all tasks were retained post drug-administration, but transfer effects to broad cognitive abilities were not seen. This study shows that combining CT with modafinil specifically elevates learning over early training sessions compared to CT with placebo and provides a proof of principle experimental paradigm for pharmacological enhancement of cognitive remediation., (Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.)

There is recognition that biomedical research into the causes of mental disorders and their treatment needs to adopt new approaches to research. Novel biomedical techniques have advanced our understanding of how the brain develops and is shaped by behaviour and environment. This has led to the advent of stratified medicine, which translates advances in basic research by targeting aetiological mechanisms underlying mental disorder. The resulting increase in diagnostic precision and targeted treatments may provide a window of opportunity to address the large public health burden, and individual suffering associated with mental disorders. While mental health and mental disorders have significant representation in the "health, demographic change and wellbeing" challenge identified in Horizon 2020, the framework programme for research and innovation of the European Commission (2014-2020), and in national funding agencies, clear advice on a potential strategy for mental health research investment is needed. The development of such a strategy is supported by the EC-funded "Roadmap for Mental Health Research" (ROAMER) which will provide recommendations for a European mental health research strategy integrating the areas of biomedicine, psychology, public health well being, research integration and structuring, and stakeholder participation. Leading experts on biomedical research on mental disorders have provided an assessment of the state of the art in core psychopathological domains, including arousal and stress regulation, affect, cognition social processes, comorbidity and pharmacotherapy. They have identified major advances and promising methods and pointed out gaps to be addressed in order to achieve the promise of a stratified medicine for mental disorders., (© 2013 Published by Elsevier B.V. and ECNP.)

Cognitive impairment is a well-documented feature of schizophrenia and represents a major impediment to the functional recovery of patients. The therapeutic strategies to improve cognition in schizophrenia have either used medications (collectively referred to as 'cognitive-enhancing drugs' in this article) or non-pharmacological training approaches ('cognitive remediation'). Cognitive-enhancing drugs have not as yet been successful and cognitive remediation has shown modest success. Therefore, we may need to explore new therapeutic paradigms to improve cognition in schizophrenia. The optimal approach may require a combination of cognitive-enhancing drugs with cognitive remediation. We review the available data from animal and human studies that provide the conceptual basis, proof-of-concept and illustrations of success of such combination strategies in experimental and clinical paradigms in other conditions. We address the major design issues relevant to the choice of the cognitive-enhancing drugs and cognitive remediation, as well as the timing and the duration of the intervention as will be relevant for schizophrenia. Finally, we address the practical realities of the development and testing of such combined approaches in the real-world clinical situation and conclude that while scientifically attractive, there are several practical difficulties to be overcome for this approach to be clinically feasible., (Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.)

Objective: Older people with a diagnosis of schizophrenia seem to show fewer benefits following cognitive remediation therapy (CRT). It is not clear whether cognitive reserve modifies the relationship with age., Methods: A total of 134 individuals with schizophrenia were pooled from one randomized control trial and one observational trial. Eighty-five participants received more than 20 sessions of CRT and 49 participants received fewer than 20 sessions of CRT or treatment as usual. Participants were divided into two groups according to their age (younger than 40 years: younger, N = 77; and 40 years or older: older, N = 57). Cognition (working memory, cognitive flexibility, and planning) was assessed at baseline and posttreatment. Premorbid IQ and vocabulary at baseline were used as cognitive reserve proxies., Results: There was a significant effect of CRT on working memory in younger but not older participants. Better premorbid IQ was associated with better working memory performance in younger participants irrespective of treatment. No significant effects of treatment or cognitive reserve were revealed in older participants. Cognitive reserve proxies did not modify CRT treatment effect., Conclusion: In conclusion, the effects of CRT were limited in older people with schizophrenia. Cognitive reserve could not be shown to influence the relationship of age with CRT efficacy. Better premorbid IQ was associated with increased practice effects on working memory in younger but not older individuals., (Copyright © 2013 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The development of Clinical Research Networks (CRN) has been central to the work conducted by Health Departments and research funders to promote and support clinical research within the NHS in the UK. In England, the National Institute for Health Research has supported the delivery of clinical research within the NHS primarily through CRN. CRN provide the essential infrastructure within the NHS for the set up and delivery of clinical research within a high-quality peer-reviewed portfolio of studies. The success of the National Cancer Research Network is summarized in Chapter 5. In this chapter progress in five other topics, and more recently in primary care and comprehensively across the NHS, is summarized. In each of the 'topic-specific' networks (Dementias and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health, Stroke) there has been a rapid and substantial increase in portfolios and in the recruitment of patients into studies in these portfolios. The processes and the key success factors are described. The CRN have worked to support research supported by pharmaceutical, biotechnology and medical device companies and there has been substantial progress in improving the speed, cost and delivery of these 'industry' studies. In particular, work to support the increased speed of set up and delivery of industry studies, and to embed this firmly in the NHS, was explored in the North West of England in an Exemplar Programme which showed substantial reductions in study set-up times and improved recruitment into studies and showed how healthcare (NHS) organizations can overcome delays in set up times when they actively manage the process. Seven out of 20 international studies reported that the first patient to be entered anywhere in the world was from the UK. In addition, the CRN have supported research management and governance, workforce development and clinical trials unit collaboration and coordination. International peer reviews of all of the CRN have been positive and resulted in the continuation of the system for a further 5 years in all cases.

The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative, funded by an R13 from the National Institute of Mental Health, seeks to enhance translational research in treatment development for impaired cognition in schizophrenia by developing tools from cognitive neuroscience into useful measures of treatment effects on behavior and brain function. An initial series of meetings focused on the selection of a new set of tasks from cognitive neuroscience for the measurement of treatment effects on specific cognitive and neural systems. Subsequent validation and optimization studies are underway and a subset of validated measures with well-characterized psychometric properties will be generally available in 2011. This article describes results of the first meeting of the second phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia, which seeks to develop imaging biomarkers and improved animal models to enhance translational research. In this meeting, we considered issues related to the use of methods such as functional magnetic resonance imaging, electroencephalography, magnetoencephalography, and transcranial magnetic simulation as biomarkers for treatment development. We explored the biological nature of the signals measured by each method, their validity and reliability as measures of cognition-related neural activity, potential confounds related to drug effects on the signal of interest, and conceptual, methodological, and pragmatic issues related to their use in preclinical, first into human, and multicenter phase II and III studies. This overview article describes the background and goals of the meeting together with a summary of the major issues discussed in more detail in the accompanying articles appearing in this issue of Biological Psychiatry., (Copyright © 2011 Society of Biological Psychiatry. All rights reserved.)

This overview describes the generation and development of the ideas that led to the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. It also describes the organization, process, and products of the first meeting. The CNTRICS initiative involves a series of three conferences that will systematically address barriers to translating paradigms developed in the basic animal and human cognitive neuroscience fields for use in translational research aimed at developing novel treatments for cognitive impairments in schizophrenia. The articles in this special section report on the results of the first conference, which used a criterion-based consensus-building process to develop a set of cognitive constructs to be targeted for translation efforts.