A systematic review of users experiences of using digital interventions within psychosis: a thematic synthesis of qualitative research.

PURPOSE: Although the development of digital mental health support for people with psychosis has been increasing, the development and opportunities to access this have been more limited compared to other mental health conditions. Qualitative research exploring the experiences of using digital interventions amongst people with psychosis is even less well developed; however, such research is crucial in capturing the experiences of using digital interventions to ensure they are meeting the needs of people with psychosis. This paper aimed to synthesise qualitative data related to the experiences of people with psychosis who have used digital interventions. METHODS: A systematic literature search was conducted of articles published between 1992 and October 2023 using PubMed, MBase, PsycINFO, & OVID Medline. Two reviewers independently reviewed and screened 268 papers. Papers that met inclusion criteria were quality assessed using The Critical Appraisal Skills Programme (CASP) qualitative studies checklist. The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) checklist was used to guide the structure of the report. RESULTS: A thematic synthesis of 19 studies revealed six overarching themes which related to different aspects and features of the digital interventions: participants' relationship with technology; the accessibility of the interventions; how the interventions could impact on individuals' awareness and management of mental health; enhanced communication and relationships; and opportunities for reflection. CONCLUSIONS: Benefits of using digital interventions are discussed. Areas for development and improvements are highlighted. Finally, recommendations for stakeholders who develop and implement digital interventions for psychosis are made.

Measurement of Adverse Events in Studies of Digital Health Interventions for Psychosis: Guidance and Recommendations Based on a Literature Search and Framework Analysis of Standard Operating Procedures.

BACKGROUND: Given the rapid expansion of research into digital health interventions (DHIs) for severe mental illness (SMI; eg, schizophrenia and other psychosis diagnoses), there is an emergent need for clear safety measures. Currently, measurement and reporting of adverse events (AEs) are inconsistent across studies. Therefore, an international network, iCharts, was assembled to systematically identify and refine a set of standard operating procedures (SOPs) for AE reporting in DHI studies for SMI. DESIGN: The iCharts network comprised experts on DHIs for SMI from seven countries (United Kingdom, Belgium, Germany, Pakistan, Australia, United States, and China) and various professional backgrounds. Following a literature search, SOPs of AEs were obtained from authors of relevant studies, and from grey literature. RESULTS: A thorough framework analysis of SOPs (n = 32) identified commonalities for best practice for certain domains, along with significant gaps in others; particularly around the classification of AEs during trials, and the provision of training/supervision for research staff in measuring and reporting AEs. Several areas which could lead to the observed inconsistencies in AE reporting and handling were also identified. CONCLUSIONS: The iCharts network developed best-practice guidelines and a practical resource for AE monitoring in DHI studies for psychosis, based on a systematic process which identified common features and evidence gaps. This work contributes to international efforts to standardize AE measurement and reporting in this emerging field, ensuring that safety aspects of DHIs for SMI are well-studied across the translational pathway, with monitoring systems set-up from the outset to support safe implementation in healthcare systems.

Intact Mismatch Negativity Responses in Clinical High Risk for Psychosis and First-Episode Psychosis: Evidence From Source-Reconstructed Event-Related Fields and Time-Frequency Data.

BACKGROUND: This study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps. METHODS: Magnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl's gyri and bilateral superior temporal gyri. RESULTS: Significant magnetic MMN responses were found across participants in the bilateral Heschl's gyri and bilateral superior temporal gyri. However, MMN amplitude as well as time-frequency and intertrial phase coherence responses were intact in CHR-P participants and FEP patients compared with healthy control participants. Furthermore, MMN deficits were not related to persistent attenuated psychotic symptoms or transitions to psychosis in CHR-P participants. CONCLUSIONS: Our data suggest that magnetic MMN responses in magnetoencephalography data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants.

Investigating the relationship between specific negative symptoms and metacognitive functioning in psychosis: A systematic review.

BACKGROUND: Disrupted metacognition is implicated in development and maintenance of negative symptoms, but more fine-grained analyses would inform precise treatment targeting for individual negative symptoms. AIMS: This systematic review identifies and examines datasets that test whether specific metacognitive capacities distinctly influence negative symptoms. MATERIALS & METHODS: PsycINFO, EMBASE, Medline and Cochrane Library databases plus hand searching of relevant articles, journals and grey literature identified quantitative research investigating negative symptoms and metacognition in adults aged 16+ with psychosis. Authors of included articles were contacted to identify unique datasets and missing information. Data were extracted for a risk of bias assessment using the Quality in Prognostic Studies tool. RESULTS: 85 published reports met criteria and are estimated to reflect 32 distinct datasets and 1623 unique participants. The data indicated uncertainty about the relationship between summed scores of negative symptoms and domains of metacognition, with significant findings indicating correlation coefficients from 0.88 to -0.23. Only eight studies investigated the relationship between metacognition and individual negative symptoms, with mixed findings. Studies were mostly moderate-to-low risk of bias. DISCUSSION: The relationship between negative symptoms and metacognition is rarely the focus of studies reviewed here, and negative symptom scores are often summed. This approach may obscure relationships between metacognitive domains and individual negative symptoms which may be important for understanding how negative symptoms are developed and maintained. CONLCLUSION: Methodological challenges around overlapping participants, variation in aggregation of negative symptom items and types of analyses used, make a strong case for use of Individual Participant Data Meta-Analysis to further elucidate these relationships.

Investigating the relationship between negative symptoms and metacognitive functioning in psychosis: An individual participant data meta-analysis.

PURPOSE: Negative symptoms are a persistent, yet under-explored problem in psychosis. Disturbances in metacognition are a potential causal factor in negative symptom development and maintenance. This meta-analysis uses individual participant data (IPD) from existing research to assess the relationship between negative symptoms and metacognition treated as summed scores and domains. METHODS: Data sets containing individuals with negative symptoms and metacognition data, aged 16+ with psychosis, were identified according to pre-specific parameters. IPD integrity and completeness were checked and data were synthesized in two-stage meta-analyses of each negative symptoms cluster compared with metacognition in seemingly unrelated regression using restricted maximum likelihood estimation. Planned and exploratory sensitivity analyses were also conducted. RESULTS: Thirty-three eligible data sets were identified with 21 with sufficient similarity and availability to be included in meta-analyses, corresponding to 1301 participants. The strongest relationships observed were between summed scores of negative symptoms and metacognition. Metacognitive domains of self-reflectivity and understanding others' minds, and expressive negative symptoms emerged as significant in some meta-analyses. The uncertainty of several effect estimates increased significantly when controlling for covariates. CONCLUSIONS: This robust meta-analysis highlights the impact of using summed versus domain-specific scores of metacognition and negative symptoms, and relationships are not as clear-cut as once believed. Findings support arguments for further differentiation of negative symptom profiles and continued granular exploration of the relationship between metacognition and negative symptoms.

Using EMPOWER in daily life: a qualitative investigation of implementation experiences.

BACKGROUND: Digital self-management tools blended with clinical triage and peer support have the potential to improve access to early warning signs (EWS) based relapse prevention in schizophrenia care. However, the implementation of digital interventions in psychosis can be poor. Traditionally, research focused on understanding how people implement interventions has focused on the perspectives of mental health staff. Digital interventions are becoming more commonly used by patients within the context of daily life, which means there is a need to understand implementation from the perspectives of patients and carers. METHODS: Semi-structured one-on-one interviews with 16 patients who had access to the EMPOWER digital self-management intervention during their participation in a feasibility trial, six mental health staff members who supported the patients and were enrolled in the trial, and one carer participant. Interviews focused on understanding implementation, including barriers and facilitators. Data were coded using thematic analysis. RESULTS: The intervention was well implemented, and EMPOWER was typically perceived positively by patients, mental health staff and the carer we spoke to. However, some patients reported negative views and reported ideas for intervention improvement. Patients reported valuing that the app afforded them access to things like information or increased social contact from peer support workers that went above and beyond that offered in routine care. Patients seemed motivated to continue implementing EMPOWER in daily life when they perceived it was creating positive change to their wellbeing, but seemed less motivated if this did not occur. Mental health staff and carer views suggest they developed increased confidence patients could self-manage and valued using the fact that people they support were using the EMPOWER intervention to open up conversations about self-management and wellbeing. CONCLUSIONS: The findings from this study suggest peer worker supported digital self-management like EMPOWER has the potential to be implemented. Further evaluations of these interventions are warranted, and conducting qualitative research on the feasibility gives insight into implementation barriers and facilitators, improving the likelihood of interventions being usable. In particular, the views of patients who demonstrated low usage levels would be valuable.

A case series study of compassion-focused therapy for distressing experiences in psychosis.

OBJECTIVES: Compassion-focused therapy (CFT) is an evolution-informed biopsychosocial approach that seeks to cultivate attachment and care motivational systems and their psychophysiological regulators. These can counteract some of the harmful effects of social threat, inferiority, shame, self-criticism and depression, which are common in people with psychosis and undermine their well-being, social trust and ability to feel safe. This study aimed to test the acceptability of a novel manualized individual CFT intervention for psychosis (CFTp). DESIGN: A non-concurrent, multiple-baseline, case series design, with three phases: baseline, intervention and follow-up. METHODS: The 26-session CFTp intervention was provided for a sample of eight people with distressing psychotic experiences and a psychosis-related diagnosis. The study aimed to assess acceptability of CFTp and to test clinically reliable improvements while receiving the intervention, compared to a baseline period. RESULTS: Seven of eight participants completed the therapy, and clinically reliable improvements were found at both the single-case and group level of analysis. At the single-case level, over half the participants showed improvements in depression (5/7), stress (5/7), distress (5/7), anxiety (4/7) and voices (3/5). One participant showed a deterioration in anxiety (1/7) and dissociation (1/7). At the group level (n = 7), there were significant improvements in depression, stress, distress, voices and delusions. The improvements in voices, delusions and distress were sustained at 6- to 8-week follow-up, but depression and stress dropped slightly to trend-level improvements. CONCLUSIONS: CFTp is a feasible and acceptable intervention for psychosis, and further investigation is warranted with a randomized controlled trial.

Experiences of Stigma and Discrimination in Borderline Personality Disorder: A Systematic Review and Qualitative Meta-Synthesis.

Individuals with a diagnosis of borderline personality disorder (BPD) typically experience discrimination and stigma, resulting in poor identification and delayed care. We conducted a review to examine and synthesize qualitative studies exploring experiences of stigma and discrimination among individuals with BPD. In August 2021, we systematically searched the following databases: Embase, Medline, Cochrane Library, PsycINFO, and Cinhal. We also hand searched reference lists and Google Scholar. We then synthesized studies using meta-ethnography. We included seven articles in the study, all of high or moderate quality. Five themes were identified: (1) resistance from clinicians (withholding information), (2) othering, (3) negative impact on self-image/esteem, (4) hopelessness surrounding the perceived permanency of BPD, and (5) feeling like a burden. This review highlights the need for improved understanding of BPD across health care services. We also discussed the need to introduce a standardized pathway of care across health services following a BPD diagnosis.

Thalamo-cortical circuits during sensory attenuation in emerging psychosis: a combined magnetoencephalography and dynamic causal modelling study.

Evidence suggests that schizophrenia (ScZ) involves impairments in sensory attenuation. It is currently unclear, however, whether such deficits are present during early-stage psychosis as well as the underlying network and the potential as a biomarker. To address these questions, Magnetoencephalography (MEG) was used in combination with computational modeling to examine M100 responses that involved a "passive" condition during which tones were binaurally presented, while in an "active" condition participants were asked to generate a tone via a button press. MEG data were obtained from 109 clinical high-risk for psychosis (CHR-P) participants, 23 people with a first-episode psychosis (FEP), and 48 healthy controls (HC). M100 responses at sensor and source level in the left and right thalamus (THA), Heschl's gyrus (HES), superior temporal gyrus (STG) and right inferior parietal cortex (IPL) were examined and dynamic causal modeling (DCM) was performed. Furthermore, the relationship between sensory attenuation and persistence of attenuated psychotic symptoms (APS) and transition to psychosis was investigated in CHR-P participants. Sensory attenuation was impaired in left HES, left STG and left THA in FEP patients, while in the CHR-P group deficits were observed only in right HES. DCM results revealed that CHR-P participants showed reduced top-down modulation from the right IPL to the right HES. Importantly, deficits in sensory attenuation did not predict clinical outcomes in the CHR-P group. Our results show that early-stage psychosis involves impaired sensory attenuation in auditory and thalamic regions but may not predict clinical outcomes in CHR-P participants.

Exploring digital cognitive behavioural therapy for insomnia in an early intervention in psychosis service - A study protocol for an initial feasibility study with process evaluation.

AIM: Early psychosis may be a critical time at which clinical trajectories are still evolving, and sleep interventions hold promise to improve outcomes at this stage. Although cognitive behavioural therapy (CBT) for insomnia shows promise in psychosis, there has been limited evaluation of delivery within current care. This study aims to evaluate the feasibility and acceptability of providing fully-automated digital CBT for insomnia (CBT-I) within an early intervention in psychosis service. METHODS: We will conduct a single-arm feasibility trial within an early psychosis intervention service, and up to 40 individuals experiencing a first episode of psychosis and with evidence of insomnia can be enrolled (May 2021 - August 2022). Additional service user inclusion criteria are capacity to consent and access to a suitable technological device to access digital CBT. Participants will be offered access to a fully-automated digital CBT-I program (Sleepio) delivered using web and/or mobile app. The study comprises pre- and post- intervention questionnaire assessments and interviews with service users and staff to provide initial outcome signals. RESULTS: Quantitative questionnaire data will be analysed descriptively, alongside rates of eligibility, consent, uptake and completion. Qualitative data will be analysed using thematic analysis. Results will be used to develop a logic model describing feasibility and implementation. CONCLUSIONS: From this study, we hope to better understand how to deliver digital CBT for insomnia within an early intervention in psychosis service. This study will help inform further research, including how best to support staff in using Sleepio, and inform the design of subsequent trials in this area.

General and age-specific fertility rates in non-affective psychosis: population-based analysis of Scottish women.

PURPOSE: Women diagnosed with non-affective psychosis have a lower general fertility rate (GFR) and age-specific fertility rate (ASFR) than women in the general population. Contemporary data on GFR in this group remain limited, despite substantive changes in prescribing and management. We calculated contemporary estimates of the GFR and ASFR for women diagnosed with non-affective psychosis compared with the general population of women without this diagnosis. METHODS: A population-based design combined routinely collected historical maternity and psychiatric data from two representative areas of Scotland. Women were included from the NHS Grampian or Greater Glasgow and Clyde areas and were aged 15-44 between 2005 and 2013 inclusive. The 'exposed' group had a diagnosis of non-affective psychosis (ICD-10 F20-F29) and was compared to the general population of 'unexposed' women in the same geographical areas. RESULTS: Annual GFR between 2005 and 2013 for women with non-affective psychosis varied from 9.6 to 21.3 live births/1000 women per year in the exposed cohort and 52.7 to 57.8 live births/1000 women per year in the unexposed cohort, a rate ratio (RR) of 0.28 [p < 0.001; 95% CI (0.24, 0.32)]. ASFR for all 5-year age groups was lower in the exposed cohort than amongst unexposed women. CONCLUSION: We highlight continued low fertility rates in women with a diagnosis of non-affective psychosis, despite widespread availability of prolactin-sparing atypical antipsychotics. Accurate estimation of fertility rates remains crucial in developing needs-matched perinatal care for these women. Methodological improvements using routine datasets to investigate perinatal mental health are also urgently needed.

Investigating temporal and prosodic markers in clinical high-risk for psychosis participants using automated acoustic analysis.

AIM: Language disturbances are a candidate biomarker for the early detection of psychosis. Temporal and prosodic abnormalities have been observed in schizophrenia patients, while there is conflicting evidence whether such deficits are present in participants meeting clinical high-risk for psychosis (CHR-P) criteria. METHODS: Clinical interviews from CHR-P participants (n = 50) were examined for temporal and prosodic metrics and compared against a group of healthy controls (n = 17) and participants with affective disorders and substance abuse (n = 23). RESULTS: There were no deficits in acoustic variables in the CHR-P group, while participants with affective disorders/substance abuse were characterized by slower speech rate, longer pauses and higher unvoiced frames percentage. CONCLUSION: Our finding suggests that temporal and prosodic aspects of speech are not impaired in early-stage psychosis. Further studies are required to clarify whether such abnormalities are present in sub-groups of CHR-P participants with elevated psychosis-risk.

Digital Interventions for Psychological Well-being in University Students: Systematic Review and Meta-analysis.

BACKGROUND: Life at university provides important opportunities for personal growth; however, this developmental phase also coincides with the peak period of risk for the onset of mental health disorders. In addition, specific university lifestyle factors, including impaired sleep and academic and financial stress, are known to exacerbate psychological distress in students. As a result, university students have been identified as a vulnerable population who often experience significant barriers to accessing psychological treatment. Digital psychological interventions are emerging as a promising solution for this population, but their effectiveness remains unclear. OBJECTIVE: This systematic review and meta-analysis aimed to assess digital interventions targeting psychological well-being among university students. METHODS: Database searches were conducted on December 2, 2021, via Embase, MEDLINE, PsycINFO, and Web of Science. RESULTS: A total of 13 eligible studies were identified, 10 (77%) of which were included in the meta-analysis. Mean pre-post effect sizes indicated that such interventions led to small and significant improvement in psychological well-being (Hedges g=0.32, 95% CI 0.23-0.4; P<.001). These effects remained, albeit smaller, when studies that included a wait-list control group were excluded (Hedges g=0.22, 95% CI 0.08-0.35; P=.002). An analysis of acceptance and commitment therapy approaches revealed small and significant effects (k=6; Hedges g=0.35, 95% CI 0.25-0.45; P<.001). CONCLUSIONS: Digital psychological interventions hold considerable promise for university students, although features that optimize service delivery and outcomes require further assessment. TRIAL REGISTRATION: PROSPERO CRD42020196654; https:/www.crd.york.ac.uk/prospero/display_record.php?RecordID=196654.

Recruiting and exploring vulnerabilities among young people at risk, or in the early stages of serious mental illness (borderline personality disorder and first episode psychosis).

Introduction: Many gaps exist in our understanding of the developmental pathways to severe mental illness (SMI), including borderline personality disorder (BPD) and psychosis. However, those who have experienced adverse childhood experiences (ACEs) are at an increased risk and there is evidence to suggest that one of the earliest markers is emotional dysregulation. An area which has received relatively less research attention is the role neurodevelopmental disorders (NDDs) play. The aim of this feasibility study was therefore to explore the clinical profiles of young people early in the course of SMI, including their profiles of ACEs, emotional regulation difficulties, borderline personality traits and NDDs. Methods: A cross-sectional study of young people (aged 15-25) at risk of SMI, currently being seen within NHS mental health services, was conducted. This included those with early symptoms of psychosis and/or BPD as assessed by diagnostic interview. Eligible participants self-completed a battery of sociodemographic, clinical, and psychological measures in the company of a researcher. This included assessments of: symptoms of NDDs; borderline pathology traits; ACEs; and difficulties in emotional regulation. Statistical analyses included Mann-Whitney U tests and multiple regression. Results: Of the 118 potentially eligible participants who were referred, 48 were ultimately included in the study. Young people early in the course of SMI reported a high prevalence of ACEs and deficits in emotional regulation. In total, 79% met criteria for attention deficit hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD). Emotional dysregulation was found to significantly mediate the association between both ACEs and the frequency of NDDs and borderline personality traits, however given the small sample size these results are preliminary in nature. Conclusion: Young people early in the course of SMI are at an increased risk of experiencing multiple childhood adversities and our results indicate a high prevalence of NDDs amongst them. Emotional dysregulation emerged as a potentially significant early marker of future clinical severity. We suggest that the clinical implications of our findings include routine screening for NDDs and ACEs and an increased recognition of the significance of emotional dysregulation. However, larger scale longitudinal studies are needed to investigate these preliminary findings further.

Hippocampal structural alterations in early-stage psychosis: Specificity and relationship to clinical outcomes.

Hippocampal dysfunctions are a core feature of schizophrenia, but conflicting evidence exists whether volumetric and morphological changes are present in early-stage psychosis and to what extent these deficits are related to clinical trajectories. In this study, we recruited individuals at clinical high risk for psychosis (CHR-P) (n = 108), patients with a first episode of psychosis (FEP) (n = 37), healthy controls (HC) (n = 70) as well as a psychiatric control group with substance abuse and affective disorders (CHR-N: n = 38). MRI-data at baseline were obtained and volumetric as well as vertex analyses of the hippocampus were carried out. Moreover, volumetric changes were examined in the amygdala, caudate, nucleus accumbens, pallidum, putamen and thalamus. In addition, we obtained follow-up functional and symptomatic assessments in CHR-P individuals to examine the question whether anatomical deficits at baseline predicted clinical trajectories. Our results show that the hippocampus is the only structure showing significant volumetric decrease in early-stage psychosis, with FEPs showing significantly smaller hippocampal volumes bilaterally alongside widespread shape changes in the vertex analysis. For the CHR-P group, volumetric decreases were confined to the left hippocampus. However, hippocampal alterations in the CHR-P group were not robustly associated with clinical outcomes, including the persistence of attenuated psychotic symptoms and functional trajectories. Accordingly, our findings highlight that dysfunctions in hippocampal anatomy are an important feature of early-stage psychosis which may, however, not be related to clinical outcomes in CHR-P participants.

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

BACKGROUND: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. OBJECTIVE: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? DESIGN: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. SETTINGS: Glasgow, UK, and Melbourne, Australia. PARTICIPANTS: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. INTERVENTIONS: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. MAIN OUTCOME MEASURES: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. RESULTS: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. LIMITATIONS: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. CONCLUSIONS: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. FUTURE WORK: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). TRIAL REGISTRATION: This trial is registered as ISRCTN99559262. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

WHAT WAS THE PROBLEM?: Relapse is a considerable problem for people with a diagnosis of schizophrenia. Relapse can be predicted by early warning signs that are unique to the person. They include withdrawal, fear and paranoia. WHAT WAS THE QUESTION?: Is it possible to investigate the effectiveness of an intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? WHAT DID WE DO?: We spoke with 88 mental health staff, 40 carers and 21 service users before we designed a system that used a mobile phone to help people monitor early warning signs. We included peer support to help people using the system reflect on their experiences. We hoped the overall system, called EMPOWER, would help people to be more in charge of their mental health. After consenting 86 people to the study, we were able to randomly assign 73 people either to use the EMPOWER system (42 people) or to receive their normal treatment alone (31 people). We used research measures over 1 year to help us better understand people's experiences. We also involved carers (for example family or friends) and mental health service providers in the research. WHAT DID WE FIND?: We found that it was possible to recruit people to the study and to gather research data. We also found that people used the EMPOWER system and found it acceptable. We found that those who used EMPOWER had a lower rate of relapse over 12 months than people who did not. They were also less likely to be fearful of relapse. We found that EMPOWER was likely to be cost-effective. WHAT DOES THIS MEAN?: This means that a study to investigate the effectiveness of a system to recognise and respond to early warning signs of relapse in schizophrenia is possible.

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia.

BACKGROUND: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. METHODS: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). FINDINGS: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). INTERPRETATION: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. FUNDING: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

MR-Spectroscopy of GABA and Glutamate/Glutamine Concentrations in Auditory Cortex in Clinical High-Risk for Psychosis Individuals.

Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3 Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P (n = 99), CHR-N (clinical high-risk negative, n = 32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. Results showed a marginal (p = 0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels (p = 0.029, uncorrected) in the CHR-P compared to the CHR-N group, but not relative to healthy controls (p = 0.058, uncorrected). Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores. However, in the CHR-P group, Glx levels did not predict clinical or functional outcomes. Accordingly, the findings from the present study suggest that MRS-measured GABA, glutamate and Glx levels in auditory cortex of CHR-P individuals are largely intact.

Fear of relapse in schizophrenia: a mixed-methods systematic review.

INTRODUCTION: Fears of relapse in people diagnosed with schizophrenia have long been recognised as an impediment to recovery and wellbeing. However, the extent of the empirical basis for the fear of relapse concept is unclear. A systematic review is required to collate available evidence and define future research directions. METHODS: A pre-registered systematic search (PROSPERO CRD42020196964) of four databases (PubMED, MEDLINE-Ovid, PsycINFO-Ovid, and Cochrane Central Register of Controlled Trials) was conducted from their inception to 05/04/2021. RESULTS: We found nine eligible studies. Five were quantitative (4 descriptive and 1 randomised controlled trial), and four were qualitative. The available quantitative evidence suggests that fear of relapse may have concurrent positive relationships with depression (r = 0.72) and suicide ideation (r = 0.48), and negative relationship with self-esteem (r = 0.67). Qualitative synthesis suggests that fear of relapse is a complex phenomenon with behavioural and emotional components which has both direct and indirect effects on wellbeing. CONCLUSIONS: Evidence in this area is limited and research with explicit service user and carer involvement is urgently needed to develop new and/or refine existing measurement tools, and to measure wellbeing rather than psychopathology. Nonetheless, clinicians should be aware that fear of relapse exists and appears to be positively associated with depression and suicide ideation, and negatively associated with self-esteem. Fear of relapse can include fears of losing personal autonomy and/or social/occupational functioning. It appears to impact carers as well as those diagnosed with schizophrenia.