Effects of Actissist, a digital health intervention for early psychosis: A randomized clinical trial.

Schizophrenia affects 24 million people worldwide. Digital health interventions drawing on psychological principles have been developed, but their effectiveness remains unclear. This parallel, assessor-blinded, randomized clinical trial aimed to investigate whether a cognitive behaviour therapy-informed digital health intervention (Actissist app) confers added benefit on psychotic symptoms over and above remote symptom monitoring (ClinTouch app). Participants recruited from UK community health services were randomized 1:1 to receive either Actissist plus treatment as usual (TAU) or ClinTouch plus TAU. Eligible participants were adults with schizophrenia-spectrum psychosis within five years of first episode onset meeting a criterion level of positive symptoms severity. The primary outcome was Positive and Negative Syndrome Scale (PANSS) symptoms total score at 12 weeks post-randomization. Intention-to-treat analysis included 172 participants, with 149 participants (86.6 %) providing primary outcome data. Actissist plus TAU was not associated with greater reduction than an active control remote symptom monitoring app (ClinTouch) in PANSS total score at post-randomization. There were no significant effects between groups across secondary measures. There were no serious adverse reactions. Both groups improved on the primary psychotic symptoms measure at primary end-point and on secondary measures over time. The Actissist app is safe but not superior to digital symptom monitoring.

Acceptability and experience of a smartphone symptom monitoring app for people with psychosis in China (YouXin): a qualitative study.

BACKGROUND: Access to high-quality mental healthcare remains challenging for people with psychosis globally, including China. Smartphone-based symptom monitoring has the potential to support scalable mental healthcare. However, no such tool, until now, has been developed and evaluated for people with psychosis in China. This study investigated the acceptability and the experience of using a symptom self-monitoring smartphone app (YouXin) specifically developed for people with psychosis in China. METHODS: Semi-structured interviews were conducted with 10 participants with psychosis to explore the acceptability of YouXin. Participants were recruited from the non-randomised feasibility study that tested the validity, feasibility, acceptability and safety of the YouXin app. Data analysis was guided by the theoretical framework of acceptability. RESULTS: Most participants felt the app was acceptable and easy to use, and no unbearable burdens or opportunity costs were reported. Participants found completing the self-monitoring app rewarding and experienced a sense of achievement. Privacy and data security were not major concerns for participants, largely due to trust in their treating hospital around data protection. Participants found the app easy to use and attributed this to the training provided at the beginning of the study. A few participants said they had built some form of relationship with the app and would miss the app when the study finished. CONCLUSIONS: The YouXin app is acceptable for symptom self-monitoring in people with experience of psychosis in China. Participants gained greater insights about their symptoms by using the YouXin app. As we only collected retrospective acceptability in this study, future studies are warranted to assess hypothetical acceptability before the commencement of study to provide a more comprehensive understanding of implementation.

Evaluating a smartphone-based symptom self-monitoring app for psychosis in China (YouXin): A non-randomised validity and feasibility study with a mixed-methods design.

Background: Psychosis causes a significant burden globally, including in China, where limited mental health resources hinder access to care. Smartphone-based remote monitoring offers a promising solution. This study aimed to assess the validity, feasibility, acceptability, and safety of a symptom self-monitoring smartphone app, YouXin, for people with psychosis in China. Methods: A pre-registered non-randomised validity and feasibility study with a mixed-methods design. Participants with psychosis were recruited from a major tertiary psychiatric hospital in Beijing, China. Participants utilised the YouXin app to self-monitor psychosis and mood symptoms for four weeks. Feasibility outcomes were recruitment, retention and outcome measures completeness. Active symptom monitoring (ASM) validity was tested against corresponding clinical assessments (PANSS and CDS) using Spearman correlation. Ten participants completed qualitative interviews at study end to explore acceptability of the app and trial procedures. Results: Feasibility parameters were met. The target recruitment sample of 40 participants was met, with 82.5% completing outcome measures, 60% achieving acceptable ASM engagement (completing >33% of all prompts), and 33% recording sufficient passive monitoring data to extract mobility indicators. Five ASM domains (hallucinations, suspiciousness, guilt feelings, delusions, grandiosity) achieved moderate correlation with clinical assessment. Both quantitative and qualitative evaluation showed high acceptability of YouXin. Clinical measurements indicated no symptom and functional deterioration. No adverse events were reported, suggesting YouXin is safe to use in this clinical population. Conclusions: The trial feasibility, acceptability and safety parameters were met and a powered efficacy study is indicated. However, refinements are needed to improve ASM validity and increase passive monitoring data completeness.

Technology use and attitudes towards digital mental health in people with severe mental health problems: a survey study in China.

Introduction: Digital mental health is a promising solution to support people with severe mental health problems (SMI) in China. However, little is known about the ownership rate of digital technologies and attitudes towards utilising digital health technologies (DHTs) among people with SMI in the Chinese context. The aims of this study were to understand: (i) digital technology ownership and usage rate of people with SMI in China; (ii) attitudes toward DHTs in mental health services; and (iii) how the COVID-19 pandemic has influenced views on digital mental health. Methods: A cross-sectional survey was given to outpatients with SMI using the REDCap platform. To capture a diverse sample of people with SMI, the survey was distributed across psychiatric hospitals, general hospitals with a psychiatric unit, secondary hospitals, and community healthcare centres. Results: In total, 447 survey respondents completed the survey. Relative high ownership rates of digital technologies were found, with smartphone ownership (95.5%) and access to the internet (82.1%) being the highest technologies reported. However, less than half of respondents reported frequent health-related usage of digital technologies, which may be related to the lack of knowledge in using DHTs. Most respondents found DHTs being useful for access to mental health services during the pandemic and were willing to use DHTs after the pandemic. Discussion: Our data suggest that, despite the high ownership rate of digital technologies, training programmes to improve digital health literacy for people with SMI in China are necessary to realise the full potential of digital mental health.

User engagement in a randomised controlled trial for a digital health intervention for early psychosis (Actissist 2.0 trial).

Digital Health Interventions (DHIs) can help support people with mental health problems. Achieving satisfactory levels of patient engagement is a crucial, yet often underexplored, pre-requisite for health improvement. Actissist is a co-produced DHI delivered via a smartphone app for people with early psychosis, based on Cognitive Behaviour Therapy principles. This study describes and compares engagement patterns among participants in the two arms of the Actissist 2.0 randomised controlled trial. Engagement frequency and duration were measured among participants using the Actissist app in the intervention arm (n = 87) and the ClinTouch symptom monitoring only app used as the control condition (n = 81). Overall, 47.1 % of Actissist and 45.7 % of ClinTouch users completed at least a third of scheduled alerts while active in the study. The mean frequency (77.1 versus 60.2 total responses) and the median duration (80 versus 75 days until last response) of engagement were not significantly higher among Actissist users compared to ClinTouch users. Older age, White ethnicity, using their own smartphone device and, among Actissist users, an increased sense of therapeutic alliance were significantly associated with increased engagement. Through exploiting detailed usage data, this study identifies possible participant-level and DHI-level predictors of engagement to inform the practical implementation of future DHIs.

Treatment resistance NMDA receptor pathway polygenic score is associated with brain glutamate in schizophrenia.

Dysfunction of glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia and may be particularly relevant in severe, treatment-resistant symptoms. The underlying mechanism may involve hypofunction of the NMDA receptor. We investigated whether schizophrenia-related pathway polygenic scores, composed of genetic variants within NMDA receptor encoding genes, are associated with cortical glutamate in schizophrenia. Anterior cingulate cortex (ACC) glutamate was measured in 70 participants across 4 research sites using Proton Magnetic Resonance Spectroscopy (1H-MRS). Two NMDA receptor gene sets were sourced from the Molecular Signatories Database and NMDA receptor pathway polygenic scores were constructed using PRSet. The NMDA receptor pathway polygenic scores were weighted by single nucleotide polymorphism (SNP) associations with treatment-resistant schizophrenia, and associations with ACC glutamate were tested. We then tested whether NMDA receptor pathway polygenic scores with SNPs weighted by associations with non-treatment-resistant schizophrenia were associated with ACC glutamate. A higher NMDA receptor complex pathway polygenic score was significantly associated with lower ACC glutamate (ß = -0.25, 95 % CI = -0.49, -0.02, competitive p = 0.03). When SNPs were weighted by associations with non-treatment-resistant schizophrenia, there was no association between the NMDA receptor complex pathway polygenic score and ACC glutamate (ß = 0.05, 95 % CI = -0.18, 0.27, competitive p = 0.79). These results provide initial evidence of an association between common genetic variation implicated in NMDA receptor function and ACC glutamate levels in schizophrenia. This association was specific to when the NMDA receptor complex pathway polygenic score was weighted by SNP associations with treatment-resistant schizophrenia.

A Digital System (YouXin) to Facilitate Self-Management by People With Psychosis in China: Protocol for a Nonrandomized Validity and Feasibility Study With a Mixed Methods Design.

BACKGROUND: Psychosis is one of the most disabling mental health conditions and causes significant personal, social, and economic burden. Accurate and timely symptom monitoring is critical to offering prompt and time-sensitive clinical services. Digital health is a promising solution for the barriers encountered by conventional symptom monitoring approaches, including accessibility, the ecological validity of assessments, and recall bias. However, to date, there has been no digital health technology developed to support self-management for people with psychosis in China. OBJECTIVE: We report the study protocol to evaluate the validity, feasibility, acceptability, usability, and safety of a symptom self-monitoring smartphone app (YouXin; Chinese name ) for people with psychosis in China. METHODS: This is a nonrandomized validity and feasibility study with a mixed methods design. The study was approved by the University of Manchester and Beijing Anding Hospital Research Ethics Committee. YouXin is a smartphone app designed to facilitate symptom self-monitoring for people with psychosis. YouXin has 2 core functions: active monitoring of symptoms (ie, smartphone survey) and passive monitoring of behavioral activity (ie, passive data collection via embedded smartphone sensors). The development process of YouXin utilized a systematic coproduction approach. A series of coproduction consultation meetings was conducted by the principal researcher with service users and clinicians to maximize the usability and acceptability of the app for end users. Participants with psychosis aged 16 years to 65 years were recruited from Beijing Anding Hospital, Beijing, China. All participants were invited to use the YouXin app to self-monitor symptoms for 4 weeks. At the end of the 4-week follow-up, we invited participants to take part in a qualitative interview to explore the acceptability of the app and trial procedures postintervention. RESULTS: Recruitment to the study was initiated in August 2022. Of the 47 participants who were approached for the study from August 2022 to October 2022, 41 participants agreed to take part in the study. We excluded 1 of the 41 participants for not meeting the inclusion criteria, leaving a total of 40 participants who began the study. As of December 2022, 40 participants had completed the study, and the recruitment was complete. CONCLUSIONS: This study is the first to develop and test a symptom self-monitoring app specifically designed for people with psychosis in China. If the study shows the feasibility of YouXin, a potential future direction is to integrate the app into clinical workflows to facilitate digital mental health care for people with psychosis in China. This study will inform improvements to the app, trial procedures, and implementation strategies with this population. Moreover, the findings of this trial could lead to optimization of digital health technologies designed for people with psychosis in China. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45170.

Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial.

Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed.

The association between peripheral inflammation, brain glutamate and antipsychotic response in Schizophrenia: Data from the STRATA collaboration.

Glutamate and increased inflammation have been separately implicated in the pathophysiology of schizophrenia and the extent of clinical response to antipsychotic treatment. Despite the mechanistic links between pro-inflammatory and glutamatergic pathways, the relationships between peripheral inflammatory markers and brain glutamate in schizophrenia have not yet been investigated. In this study, we tested the hypothesis that peripheral levels of pro-inflammatory cytokines would be positively associated with brain glutamate levels in schizophrenia. Secondary analyses determined whether this relationship differed according to antipsychotic treatment response. The sample consisted of 79 patients with schizophrenia, of whom 40 were rated as antipsychotic responders and 39 as antipsychotic non-responders. Brain glutamate levels were assessed in the anterior cingulate cortex (ACC) and caudate using proton magnetic resonance spectroscopy (1H-MRS) and blood samples were collected for cytokine assay on the same study visit (IL-6, IL-8, IL-10, TNF- α and IFN-γ). Across the whole patient sample, there was a positive relationship between interferon-gamma (IFN-γ) and caudate glutamate levels (r = 0.31, p = 0.02). In the antipsychotic non-responsive group only, there was a positive relationship between interleukin-8 (IL-8) and caudate glutamate (r = 0.46, p = 0.01). These findings provide evidence to link specific peripheral inflammatory markers and caudate glutamate in schizophrenia and may suggest that this relationship is most marked in patients who show a poor response to antipsychotic treatment.

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers.

BACKGROUND: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation. METHOD: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α. RESULTS: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls. CONCLUSIONS: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Anterior cingulate glutamate metabolites as a predictor of antipsychotic response in first episode psychosis: data from the STRATA collaboration.

Elevated brain glutamate has been implicated in non-response to antipsychotic medication in schizophrenia. Biomarkers that can accurately predict antipsychotic non-response from the first episode of psychosis (FEP) could allow stratification of patients; for example, patients predicted not to respond to standard antipsychotics could be fast-tracked to clozapine. Using proton magnetic resonance spectroscopy (1H-MRS), we examined the ability of glutamate and Glx (glutamate plus glutamine) in the anterior cingulate cortex (ACC) and caudate to predict response to antipsychotic treatment. A total of 89 minimally medicated patients with FEP not meeting symptomatic criteria for remission were recruited across two study sites. 1H-MRS and clinical data were acquired at baseline, 2 and 6 weeks. Response was defined as >20% reduction in Positive and Negative Syndrome Scale (PANSS) Total score from baseline to 6 weeks. In the ACC, baseline glutamate and Glx were higher in Non-Responders and significantly predicted response (P < 0.02; n = 42). Overall accuracy was greatest for ACC Glx (69%) and increased to 75% when symptom severity at baseline was included in the model. Glutamate metabolites in the caudate were not associated with response, and there was no significant change in glutamate metabolites over time in either region. These results add to the evidence linking elevations in ACC glutamate metabolites to a poor antipsychotic response. They indicate that glutamate may have utility in predicting response during early treatment of first episode psychosis. Improvements in accuracy may be made by combining glutamate measures with other response biomarkers.

Cognitive function and treatment response trajectories in first-episode schizophrenia: evidence from a prospective cohort study.

OBJECTIVES: This prospective cohort study tested for associations between baseline cognitive performance in individuals early within their first episode and antipsychotic treatment of psychosis. We hypothesised that poorer cognitive functioning at the initial assessment would be associated with poorer antipsychotic response following the subsequent 6 weeks. DESIGN: Prospective cohort . SETTING: National Health Service users with a first-episode schizophrenia diagnosis, recently starting antipsychotic medication, recruited from two UK sites (King's College London, UK and University of Manchester, UK). Participants attended three study visits following screening. PARTICIPANTS: Eighty-nine participants were recruited, with 46 included in the main analysis. Participants required to be within the first 2 years of illness onset, had received minimal antipsychotic treatment, have the capacity to provide consent, and be able to read and write in English. Participants were excluded if they met remission criteria or showed mild to no symptoms. PRIMARY AND SECONDARY OUTCOME MEASURES: Antipsychotic response was determined at 6 weeks using the Positive and Negative Syndrome Scale (PANSS), with cognitive performance assessed at each visit using the Brief Assessment of Cognition in Schizophrenia (BACS). The groups identified (responders and non-responders) from trajectory analyses, as well as from >20% PANSS criteria, were compared on baseline BACS performance. RESULTS: Trajectory analyses identified 84.78% of the sample as treatment responsive, and the remaining 15.22% as treatment non-responsive. Unadjusted and adjusted logistic regressions observed no significant relationship between baseline BACS on subscale and total performance (BACS t-score: OR=0.98, p=0.620, Cohen's d=0.218) and antipsychotic response at 6 weeks. CONCLUSIONS: This investigation identified two clear trajectories of treatment response in the first 6 weeks of antipsychotic treatment. Responder and non-responder groups did not significantly differ on performance on the BACS, suggesting that larger samples may be required or that an association between cognitive performance and antipsychotic response is not observable in the first 2 years of illness onset. TRIAL REGISTRATION NUMBER: REC: 17/NI/0209.

Mental health professionals views and the impact of COVID-19 pandemic on implementing digital mental health in China: A nationwide survey study.

Background: Using digital health technologies (DHTs) to deliver and augment healthcare is an innovative way to solve common challenges that the mental healthcare setting faces. Despite China's rapid development of DHT, a comprehensive understanding of staff views of DHTs is lacking, which limited the evidence to support implementation strategies. In the current study, we aim to: (i) investigate staff attitudes towards digital technology for mental health problems in China; (ii) explore staff's views on the facilitators and barriers regarding uptake and adoption of digital technology in mental health services in China; and (iii) understand how the COVID-19 pandemic has changed staff views on digital mental health. Methods: An online survey was conducted to explore staff attitudes towards implementing DHTs in China. Descriptive statistics were conducted to summarise quantitative data. Free-text data were analysed using qualitative content analysis. Results: 1270 mental health professionals completed the survey. Respondents reported low levels of knowledge of DHTs and moderate levels of accessibility of DHTs in their hospitals. Respondents expressed positive attitudes towards DHTs and demonstrated moderate levels of perceived feasibility and acceptability of implementing DHTs in clinical services. As expected, respondents reported that the COVID-19 pandemic caused significant impacts on their clinical services, and almost all respondents deemed DHTs useful for services provision during the pandemic and were willing to apply such technologies in clinical services after the pandemic. Conclusions: Despite the Chinese mental health staff expressed positive attitudes towards implementing DHTs in clinical practice, most of the staff lacked sufficient knowledge to provide such services. These findings highlight the need to develop implementation strategies such as training programmes and dissemination of research evidence to support the translation of research.

Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study.

Impaired cognition is associated with lower quality of life and poor outcomes in schizophrenia. Brain glutamate may contribute to both clinical outcomes and cognition, but these relationships are not well-understood. We studied a multicentre cohort of 85 participants with non-affective psychosis using proton magnetic resonance spectroscopy. Glutamate neurometabolites were measured in the anterior cingulate cortex (ACC). Cognition was assessed using the Brief Assessment for Cognition in Schizophrenia (BACS). Patients were categorised as antipsychotic responders or non-responders based on treatment history and current symptom severity. Inverted U-shaped associations between glutamate or Glx (glutamate + glutamine) with BACS subscale and total scores were examined with regression analyses. We then tested for an interaction effect of the antipsychotic response group on the relationship between glutamate and cognition. ACC glutamate and Glx had a positive linear association with verbal memory after adjusting for age, sex and chlorpromazine equivalent dose (glutamate, ß = 3.73, 95% CI = 1.26-6.20, P = 0.004; Glx, ß = 3.38, 95% CI = 0.84-5.91, P = 0.01). This association did not differ between good and poor antipsychotic response groups. ACC glutamate was also positively associated with total BACS score (ß = 3.12, 95% CI = 0.01-6.23, P = 0.046), but this was not significant after controlling for antipsychotic dose. Lower glutamatergic metabolites in the ACC were associated with worse verbal memory, and this relationship was independent of antipsychotic response. Further research on relationships between glutamate and cognition in antipsychotic responsive and non-responsive illness could aid the stratification of patient groups for targeted treatment interventions.

Acceptability of reducing sedentariness using a mobile-phone application based on 'if then' plans for people with psychosis: A focus-group study conducted in North West England, UK.

OBJECTIVE: To understand the acceptability of (a) reducing sedentary-behaviour in people with psychosis using 'if-then' plans and (b) the proposed app content. DESIGN: Qualitative acceptability study. METHOD: Three structured focus-groups and an interview were conducted with eight participants who had experience of a psychotic episode. They discussed sedentary-behaviour, being more active, critical situations in which they may be tempted to be sedentary and solutions to these (the if-then plans), and a mock-up of the mobile application. The Theoretical Framework of Acceptability (TFA) was used to analyse qualitatively the transcripts. RESULTS: All TFA constructs were coded in each of the transcripts. The idea of reducing sedentary-behaviour was acceptable to people with psychosis, participants knew the importance of being more active, however it is not always their main priority. Likewise, the proposed content of the app was found to be acceptable, with participants already using some of the proposed solutions. CONCLUSION: This was the first study to use the TFA framework to assess the acceptability of an app that uses critical situations and solutions ('if-then plans') to help reduce sedentary behaviour for people with psychosis. In this sample (male, English speaking mainly white people), participants understood the benefits of being more active. However, reducing sedentary-behaviour is not the main priority of this population and being sedentary has benefits when their mental-health is bad.

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.

Digital screening for postnatal depression: mixed methods proof-of-concept study.

BACKGROUND: Depression during the postnatal year is prevalent in mothers (17%) and fathers (9%), and suicide is the leading cause of maternal death in this period. Lifelong costs and consequences of untreated postnatal depression (PND) are high due to impacts on infants as well as parents. We aimed to improve access to PND treatment using digital screening. We developed a smartphone app (ClinTouch DAWN-P) that allows parents to monitor their mood daily with the Edinburgh Postnatal Depression Scale (EPDS), uploading responses in real-time to a secure server. We evaluated the app's feasibility, acceptability, validity and safety in a proof-of-concept study. METHODS: Pregnant women (≥ 36 weeks gestation) and partners were recruited from antenatal services and invited to complete daily EPDS assessments via the ClinTouch DAWN-P app until 6 weeks postpartum. Participants completed standard paper-based EPDS at two time points for validity comparisons. We examined app acceptability and usability at 6 weeks postpartum with qualitative interviews, examined using framework analysis, and the abridged Mobile App Rating Scale (convergent mixed methods design). RESULTS: Most (96%) eligible pregnant women approached were keen to try the app. Participating mothers (n = 15) and partners/fathers (n = 8) found the app easy to use, and 91% continued to use it for the full study period. Overall, 67% of daily app-based assessments were completed, with a history of depression predicting lower app usage. Participants suggested modifications to the app and its deployment to improve usability (e.g., extending the response window and including feedback and parenting advice). The validity of app-based responses was confirmed by high agreement with standard EPDS. App-based and paper-based ratings showed perfect agreement in identifying cases of likely PND. There were no serious adverse events relating to app use. CONCLUSIONS: Digital PND screening appears feasible, acceptable, valid and safe. It also benefits from being remotely delivered: we enrolled all participants remotely during the first COVID-19 lockdown. Use of digital screening could address known shortcomings of conventional health visitor-delivered screening such as limited staff time, parental unwillingness to disclose difficulties to a professional, lack of partner/father screening, and language barriers. TRIAL REGISTRATION: The study was prospectively registered (Clinicaltrials.gov: NCT04279093 ).

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.

Cross-sectional study comparing cognitive function in treatment responsive versus treatment non-responsive schizophrenia: evidence from the STRATA study.

BACKGROUND: 70%-84% of individuals with antipsychotic treatment resistance show non-response from the first episode. Emerging cross-sectional evidence comparing cognitive profiles in treatment resistant schizophrenia to treatment-responsive schizophrenia has indicated that verbal memory and language functions may be more impaired in treatment resistance. We sought to confirm this finding by comparing cognitive performance between antipsychotic non-responders (NR) and responders (R) using a brief cognitive battery for schizophrenia, with a primary focus on verbal tasks compared against other measures of cognition. DESIGN: Cross-sectional. SETTING: This cross-sectional study recruited antipsychotic treatment R and antipsychotic NR across four UK sites. Cognitive performance was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). PARTICIPANTS: One hundred and six participants aged 18-65 years with a diagnosis of schizophrenia or schizophreniform disorder were recruited according to their treatment response, with 52 NR and 54 R cases. OUTCOMES: Composite and subscale scores of cognitive performance on the BACS. Group (R vs NR) differences in cognitive scores were investigated using univariable and multivariable linear regressions adjusted for age, gender and illness duration. RESULTS: Univariable regression models observed no significant differences between R and NR groups on any measure of the BACS, including verbal memory (ß=-1.99, 95% CI -6.63 to 2.66, p=0.398) and verbal fluency (ß=1.23, 95% CI -2.46 to 4.91, p=0.510). This pattern of findings was consistent in multivariable models. CONCLUSIONS: The lack of group difference in cognition in our sample is likely due to a lack of clinical distinction between our groups. Future investigations should aim to use machine learning methods using longitudinal first episode samples to identify responder subtypes within schizophrenia, and how cognitive factors may interact within this. TRAIL REGISTRATION NUMBER: REC: 15/LO/0038.

Digital mental health in China: a systematic review.

Mental health problems are highly prevalent in China; however, China's mental health services lack resources to deliver high-quality care to people in need. Digital mental health is a promising solution to this short-fall in view of the population's digital literacy. In this review, we aim to: (i) investigate the effectiveness, acceptability, usability, and safety of digital health technologies (DHTs) for people with mental health problems in China; (ii) critically appraise the literature; and (iii) make recommendations for future research directions. The databases MEDLINE, PsycINFO, EMBASE, Web of Science, CNKI, WANFANG, and VIP were systemically searched for English and Chinese language articles evaluating DHTs for people with mental health problems in mainland China. Eligible studies were systematically reviewed. The heterogeneity of studies included precluded a meta-analysis. In total, 39 articles were retrieved, reporting on 32 DHTs for various mental health problems. Compared with the digital mental health field in the West, the Chinese studies targeted schizophrenia and substance use disorder more often and investigated social anxiety mediated by shame and culturally specific variants, DHTs were rarely developed in a co-production approach, and methodology quality was less rigorous. To our knowledge, this is the first systematic review focused on digital mental health in the Chinese context including studies published in both English and the Chinese language. DHTs were acceptable and usable among Chinese people with mental health problems in general, similar to findings from the West. Due to heterogeneity across studies and a paucity of robust control trial research, conclusions about the efficacy of DHTs are lacking.