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• Actissist is a cognitive behaviour therapy informed smartphone app for psychosis. • ClinTouch is a symptom monitoring app for psychosis. • In a powered RCT, Actissist did not improve psychotic symptoms more than clintouch. • Both groups showed improvement across all clinical measures. Both apps were safe. • Early psychosis patients should be given a choice of using digital symptom monitoring or digital intervention tools as part of routine care. 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. [ABSTRACT FROM AUTHOR]

Most previous studies investigating the factor structure of psychosis have focussed on chronic samples. First episode samples with longitudinal follow up are few. To investigate the stability and validity of symptom factors, a sample of 257 patients with DSM IV nonaffective psychoses were assessed using the PANSS during the acute first episode and at 3- and 18-month follow up. Exploratory factor analysis of the changes in PANSS item scores over time gave a five-factor solution. This was consistent with the solutions to factor analyses at the initial assessment and each of the follow-ups. However, there was progression over follow-up. Confirmatory factor analysis demonstrated that symptom ratings at 18-month follow-up fitted the models from existing research, in relatively chronic samples, better than the ratings at the initial assessment. A psychomotor poverty factor showed most stability over time and a positive symptom factor most change. Factors showed different associations with demographic and external variables, further supporting their validity. [Copyright &y& Elsevier]

Background: Peripheral immune markers have previously been linked to a poor response to antipsychotic medication and more severe negative symptoms at the onset of psychosis. The present study investigated the association of blood cytokines and complement markers with the presence of antipsychotic non-response and symptom severity in patients with psychosis.Methods: This cross-sectional study recruited 94 patients with schizophrenia and other psychoses, of whom 47 were defined as antipsychotic responders and 47 as antipsychotic non-responders. In all subjects we measured plasma levels of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, and IFN-γ), complement markers (C1-inhibitor, C3, C4, C3a, C3b, Bb, factor D, C5a, terminal complement complex) and high sensitivity C-reactive protein (hsCRP). Symptom severity was recorded using the Positive and Negative Syndrome scale for Schizophrenia (PANSS). Binary logistic regression tested each immune marker as predictor of response status while covarying for relevant socio-demographic variables. Correlation analyses tested the association between immune markers and the severity of symptoms.Results: Interleukin (IL)-8 significantly predicted antipsychotic non-response (OR=24.70, 95% CI, 1.35-453.23, p = 0.03). Other immune markers were not associated with antipsychotic response. IL-6, IL-8, IL-10 and TNF-α significantly positively correlated with negative psychotic symptoms.Conclusions: Higher levels of IL-8 are associated with a poor response to antipsychotic treatment. Increased cytokines levels are specifically associated with more severe negative symptoms in patients with schizophrenia and other psychoses. [ABSTRACT FROM AUTHOR]

• Depression and the avolition-apathy domain of negative symptoms were related. • The diminished emotional expression domain of negative symptoms was associated with TNF-α, longitudinally. • Depression correlated with IL-6 in cross-section. • CRP was unrelated to any symptom domain. • Minocycline did not lead to an improvement in depression or negative symptoms. Immune dysfunction has been implicated in negative symptoms of schizophrenia and also in depression. These disorders are frequently co-morbid, with some symptoms such as anhedonia and apathy common to both. The anti-inflammatory agent minocycline may be ineffective in schizophrenia, but more positive effects have been seen in depression. Our aim was to investigate the role of immune dysfunction in depression and sub-domains of negative symptoms in schizophrenia by investigating their intercorrelation and the influence of treatment with minocycline. We analysed longitudinal data from 207 patients within 5 years of onset of schizophrenia, from the randomised double-blind, placebo-controlled trial of minocycline (BeneMin). Symptom ratings and circulating IL-6, C-reactive protein (CRP) and TNF-α concentrations were collected at baseline and repeated over twelve months. The sample was not stratified by CRP prior to randomisation. Positive and Negative Syndrome Scale composite ratings of avolition-apathy and diminished expression, Calgary Depression Scale total scores, and immune markers were examined cross-sectionally using Spearman's rank, and longitudinally by linear mixed effect models that included body mass index and minocycline. Additionally, post hoc analysis of the sample stratified by elevated CRP (>1 mg/l and <10 mg/l at baseline) was carried out to assess whether minocycline had any effect on specific symptoms in an immune active sub-group of patients. Depression and avolition-apathy were significantly positively related, and depression correlated weakly with IL-6 at baseline. Diminished expression was associated with increased TNF-α both cross-sectionally and longitudinally. CRP was unrelated to any symptom domain. Minocycline did not affect any individual symptom or sub-domain in the full sample or in the immune active sub-group. IL-6 may have some specificity to depression in early schizophrenia. TNF-α may be an indicator of immune dysfunction relevant to negative symptoms, and our longitudinal findings add to this evidence. However, minocycline continues to show very little promise as a treatment for any symptom dimension of early schizophrenia. [ABSTRACT FROM AUTHOR]

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement. [ABSTRACT FROM AUTHOR]

The dysfunctional cognitive and reasoning biases which underpin psychotic symptoms are likely to present prior to the onset of a diagnosable disorder and should therefore be detectable along the psychosis continuum in individuals with schizotypal traits. Two reasoning biases, Bias Against Disconfirmatory Evidence (BADE) and Jumping to Conclusions (JTC), describe how information is selected and weighed under conditions of uncertainty during decision making. It is likely that states such as elevated stress exacerbates JTC and BADE in individuals with high schizotypal traits vulnerable to displaying these information gathering styles. Therefore, we evaluated whether stress and schizotypy interacted to predict these reasoning biases using separate samples from the US (JTC) and England (BADE). Generally speaking, schizotypal traits and stress were not independently associated with dysfunctional reasoning biases. However, across both studies, the interaction between schizotypy traits and stress significantly predicted reasoning biases such that increased stress was associated with increased reasoning biases, but only for individuals low in schizotypal traits. These patterns were observed for positive schizotypal traits (in both samples), for negative traits (in the England sample only), but not for disorganization traits. For both samples, our findings suggest that the presence of states such as stress is associated with, though not necessarily dysfunctional, reasoning biases in individuals with low schizotypy. These reasoning biases seemed, in some ways, relatively immutable to stress in individuals endorsing high levels of positive schizotypal traits. [ABSTRACT FROM AUTHOR]

• Response frequency declined over time in a digital health intervention. • Almost half of participants responded to at least a third of alerts in 12 weeks. • Older age, White ethnicity and using their own smartphone predicted engagement. • Even if participants can self-initiate use, engagement occurs mainly around prompts. • Therapeutic alliance predicted engagement duration in the Actissist arm. 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. [ABSTRACT FROM AUTHOR]

Rationale: Cognitive impairment associated with schizophrenia is a key predictor of functional outcomes. The FDA-accepted MATRICS Consensus Cognitive Battery (MCCB) is held to be the gold standard measure but there are concerns about its ease of administration, reliance on language causing problems with translation and possible practice effects. The CogState Schizophrenia Battery (SB) is suggested as a non-language-based alternative but there is no substantial, independent comparison. Objectives: The objective of this study was to assess the reliability and validity of these two assessment batteries. Methods: One hundred forty-three participants with DSM-IV schizophrenia and schizoaffective disorder were recruited into three similar studies. Each study administered MCCB and SB tests on consecutive days (baseline 1 and 2) and follow-up 3-4 weeks later. Results: Batteries' test-retest reliability was similar: SB composites correlated r = 0.66-0.78 between baselines, MCCB domains r = 0.69-0.90. Baseline 2 and follow-up SB composites correlated r = 0.65-0.80 and MCCB domains r = 0.62-0.87. MCCB tasks' practice effects (Glass' ∆ = 0.02-0.46) exceeded SB's (Glass' ∆ = 0.02-0.34). While the batteries' total scores correlated strongly ( r = 0.79-0.82), apparently equivalent cognitive domains on each battery (e.g. psychomotor-attention) correlated r = 0.22-0.60, indicating substantial differences between some supposed counterparts. Conclusions: Clinical trials using either battery would benefit from initial practice sessions to ameliorate practice effects but the SB may be more suitable to measure change in the absence of repeated baselines. The MCCB domains' better correlations with social skills performance suggest that it may have an advantage for measuring cognition in relation to functional outcome. [ABSTRACT FROM AUTHOR]

Despite the high impact of mental disorders in society, European mental health research is at a critical situation with a relatively low level of funding, and few advances been achieved during the last decade. The development of coordinated research policies and integrated research networks in mental health is lagging behind other disciplines in Europe, resulting in lower degree of cooperation and scientific impact. To reduce more efficiently the burden of mental disorders in Europe, a concerted new research agenda is necessary. The ROAMER (Roadmap for Mental Health Research in Europe) project, funded under the European Commission's Seventh Framework Programme, aims to develop a comprehensive and integrated mental health research agenda within the perspective of the European Union (EU) Horizon 2020 programme, with a translational goal, covering basic, clinical and public health research. ROAMER covers six major domains: infrastructures and capacity building, biomedicine, psychological research and treatments, social and economic issues, public health and well-being. Within each of them, state-of-the-art and strength, weakness and gap analyses were conducted before building consensus on future research priorities. The process is inclusive and participatory, incorporating a wide diversity of European expert researchers as well as the views of service users, carers, professionals and policy and funding institutions. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Diffusion tensor imaging (DTI) studies have identified changes in white matter tracts in schizophrenia patients and those at high risk of transition. Schizotypal samples represent a group on the schizophrenia continuum that share some aetiological risk factors but without the confounds of illness. The aim of the current study was to compare tract microstructural coherence as measured by fractional anisotropy (FA) between 12 psychometrically defined schizotypes and controls. We investigated bilaterally the uncinate and arcuate fasciculi (UF and AF) via a probabilistic tractography algorithm (PICo), with FA values compared between groups. Partial correlations were also examined between measures of subclinical hallucinatory/delusional experiences and FA values. Participants with schizotypal features were found to have increased FA values in the left hemisphere UF only. In the whole sample there was a positive correlation between FA values and measures of hallucinatory experience in the right AF. These findings suggest subtle changes in microstructural coherence are found in individuals with schizotypal features, but are not similar to changes predominantly observed in clinical samples. Correlations between mild hallucinatory experience and FA values could indicate increasing tract coherence could be associated with symptom formation. [Copyright &y& Elsevier]

Abstract: Suicide risk is high in early psychosis. Recent research has suggested that mood variability may be associated with levels of suicidal thoughts and behaviour. This has not been investigated in individuals during and following a first or second episode of non-affective psychosis. Repeated-measures data over 18 months from a large randomised controlled trial for cognitive behaviour therapy (N=309) were analysed using latent growth curve modelling, whereby both the variability and the level of depression, anxiety and guilt were entered as predictors of suicidality. The variability of depression, but not guilt and anxiety, predicted the course of suicidality even when controlling for a large range of potential confounders. The level of depression, anxiety and guilt for each participant also strongly predicted the development of suicidality. The findings support the theory that variability in depression may contribute to the formation of suicidal ideation and related behaviour. More variable depression may be harder to predict and intervene against, and therefore increase the likelihood that suicidality escalates. The levels of emotions may also be an important determinant. This has implications for the treatment and assessment of suicidality in early psychosis. [Copyright &y& Elsevier]

Self-esteem has been implicated in the development of psychotic phenomena, especially paranoia. Recent findings suggest that it may be useful to assess the instability of self-esteem instead of the mean score. We examined this construct as two separate factors: positive beliefs about the self (PBS) and negative beliefs about the self (NBS). Theoretical models have implicated NBS in the development of paranoia, whereas research studies have sometimes found an association between PBS and negative symptoms. The first aim of this study was to investigate associations between change in PBS and NBS, and subsequent change in paranoia and negative symptoms. The second aim was to examine whether fluctuations in PBS and NBS predicted mean paranoia levels. Data from a large sample of individuals with first-episode psychosis (n = 256) assessed at baseline, 6 weeks, 3 months and 18 months was analysed. The data suggest that changes in both PBS and NBS in the early stages of disorder are related to change in negative symptoms, but not paranoia. PBS variability and NBS mean scores significantly predicted average paranoia levels when taken from across all four time points, suggesting potential differences in the associations with psychosis of these two constructs. Self-esteem boosting interventions administered in the first 6 weeks after admission to healthcare services may improve the subsequent course of negative symptoms. [ABSTRACT FROM AUTHOR]

Much research has begun to focus on the identification of people who are at high risk of developing psychosis, and clinical services have been initiated for this population. However, only a small number of studies have reported on the efficacy of interventions for preventing or delaying the onset of psychosis. The results of prior work suggest that cognitive therapy (CT) may be an effective, well-tolerated treatment. We report on the rationale and design for a large-scale, multi-site randomized, controlled trial of CT for people who are assessed to be at high risk of psychosis because of either state or state-plus-trait risk factors. The study employs a single-blind design in which all participants receive frequent mental-state monitoring, which will efficiently detect transition to psychosis, and half are randomized to weekly sessions of CT for up to 6 months. Participants will be followed-up for a minimum of 12 months and to a maximum of 2 years. We report the characteristics of the final sample at baseline ( n = 288). Our study aimed to expand the currently limited evidence base for best practice in interventions for individuals at high risk of psychosis. [ABSTRACT FROM AUTHOR]

Abstract: Major problems with existing RCTs evaluating psychosocial interventions for psychosis and substance misuse have been identified, in particular small sample sizes, high attrition rates, and short follow up periods. With a sample size of 327 and a follow up of 2 years, the MIDAS trial in the UK is to date the largest RCT for people with psychosis and substance use and is evaluating an integrated MI and CBT (“MiCBT”) client therapy. Whilst the outcomes of the study are not yet available, data on recruitment and retention indicate that attrition rates in MIDAS are low and the majority of those allocated to treatment received a substantial number of therapy sessions. Sample characteristics are in line with those reported in epidemiological studies and are indicative of the challenges facing mental health services attempting to manage the client group: substance use is often longstanding, with frequent use at moderate or severe level and low motivation for change, and seen in the context of low levels of functioning and significant psychopathology. We conclude that this is a methodologically robust study that will have results generalisable to mental health services. [Copyright &y& Elsevier]

Objective: To assess whether clozapine is likely to be more cost-effective than other second-generation antipsychotics (SGAs) in people with schizophrenia. Methods: An integrated clinical and economic multicenter, rater-blind, randomized controlled trial (RCT) compared clozapine to the class of other SGAs, using the perspectives of the National Health Service, social support services, and patients. The practice setting was secondary and primary care in the United Kingdom; patients were followed for 1 year. Incremental cost-effectiveness ratios (ICERs), net benefit statistics, and cost acceptability curves were estimated. Results: The ICER for clozapine was £33,240 per quality-adjusted life-year (QALY) (range £23,000–70,000 for the sensitivity analyses). The proportion of simulations when clozapine was more cost-effective than other SGAs reached 50% if decision-makers are prepared to pay £30,000 to £35,000 per QALY. This is at the top of the range of acceptable willingness-to-pay values per QALY implied by decisions taken by the National Institute for Health and Clinical Excellence (NICE). Conclusions: This study adds to a limited body of evidence comparing clozapine to other SGAs and is the first economic and clinical RCT to compare clozapine to the class of other SGAs using the lower cost of generic clozapine and a pragmatic trial design. Policy decisions by the NICE suggest that additional reasons would be needed to accept clozapine as effective and efficient if it had a high probability of having ICERs more than £35,000 per QALY. The results and limitations of the analysis suggest that there is still a need for further economic evaluation of clozapine. [ABSTRACT FROM AUTHOR]

Purpose. It has recently been recognized that psychosis represents the end-point of abnormal developmental pathways. The neurodevelopmental framework, within which this observation has typically been interpreted, has a number of limitations, particularly its failure to take account of recent advances in our understanding of the psychology of unusual experiences, such as hallucinations and delusions. The purpose of the present review is to highlight the advantages of considering psychosis within the framework of mainstream developmental psychology. The approach we advocate integrates findings from neurodevelopmental research with research on typical cognitive and sociocognitive development and the psychology of psychotic symptoms. Method. We review selected research on the developmental precursors of psychosis and on the role of cognitive processes in psychotic symptoms, together with relevant literature addressing the development of these processes in healthy children, Results. Developmental psychology provides clues about the cognitive and sociocognitive abnormalities that may be involved in hallucinations and delusions. An integration of these findings with existing knowledge on the neurodevelopment of psychosis suggests new avenues of research for investigators working at both biological and psychological levels of explanation. Conclusions. The literature on typical cognitive and sociocognitive development provides a rich source of hypotheses about the ontogenetic pathways leading to psychosis. [ABSTRACT FROM AUTHOR]

We used UK CUtLASS RCT data to establish that patients’ rating of mental health improvement (baseline to week 12) correlated significantly with percentage symptom improvement (PANSS). In a regression analysis predictors of the patient’s week 12 mental health rating were percentage change in positive symptoms (PANSS), DAI score and the patient's rating of side effects. Patients in an RCT were able to subjectively rate their mental health status, validated by objective improvement on the PANSS. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

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., (© The Author(s) 2024.)

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., Competing Interests: SL is Academic lead of Mental Health in Health Innovation Manchester. SL and SB are Directors and shareholders of CareLoop Health Ltd., a spin out from the University of Manchester to develop and market digital solutions for remote monitoring using smartphones for mental health conditions, currently schizophrenia and postnatal depression. SB also reports research funding from the National Institute for Health and Care Research (NIHR) and The Wellcome Trust. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Lewis, Chen, Berry and Bucci.)

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., (© 2023. Springer Nature Limited.)

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., (©Xiaolong Zhang, Shôn Lewis, Lesley-Anne Carter, Sandra Bucci. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.09.2023.)

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., Competing Interests: SL and SB are Directors and Shareholders of CareLoop Health Ltd., a for-profit company that develops and markets digital therapeutics for mental health problems., (© 2022 Published by Elsevier B.V.)

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, β = 3.73, 95% CI = 1.26-6.20, P = 0.004; Glx, β = 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 (β = 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., (© 2022. The Author(s).)

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., Competing Interests: Declaration of interests AIG reports personal fees from University of Manchester, personal fees from University of Exeter, personal fees from British Association for Behavioural and Cognitive Psychotherapies and other interests with UK National Health Service (NHS) Education for Scotland outside the submitted work. JA, SL, and SB report other interests with CareLoop Health, outside the submitted work. SB reports grants from the Medical Research Council and UK National Institute for Health Research (NIHR) during the conduct of the study. SL reports grants from the UK Medical Research Council (MRC) during the conduct of the study. JA reports grants from MRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR, and the US National Institute for Health, and was a Fellow of the Alan Turing Institute during the conduct of the study. AB reports personal fees from Bayer, Merck, Janssen, Novartis, Sword Health, Amgen, and Daiichi Sankyo outside the submitted work. JF reports grants from National Health and Medical Research Council (Australia) during the conduct of the study and other interests with Melbourne Health (NorthWestern Mental Health) outside the submitted work. HMcL reports grants from NIHR Health Technology Assessment (HTA) during the conduct of the study, and grants with Academy of Medical Sciences, Glasgow Children's Hospital Charity, and Scotland's Chief Scientist's Office. CM reports grants from National Health and Medical Research Council (Australia) during the conduct of the study. JN reports grants from the University of Aberdeen and the University of Edinburgh during the conduct of the study and declares membership of the following NIHR boards: Cardio Pulmonary Resusitation decision making committee; HTA commissioning board; HTA commissioning sub-board (expression of interest); HTA funding boards policy group; HTA general board; HTA post-board funding teleconference; NIHR clinical trials unit standing advisory committee; NIHR HTA and Efficacy Mechanism Evaluation editorial board; pre-exposure prophylaxis impact review panel. PF is a member of the HTA mental health prioritisation panel. CW reports grants from NIHR during the conduct of the study and from the Royal College of Psychiatrists, and other interests with Five Areas outside the submitted work. AY reports an NIHR Senior Investigator Grant. JG reports grants from the National Health Medical Research Council. All other authors declare no competing interests., (Copyright © 2022 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.)

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 )., (© 2022. The Author(s).)

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).

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

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.

The variability in the response to antipsychotic medication in schizophrenia may reflect between-patient differences in neurobiology. Recent cross-sectional neuroimaging studies suggest that a poorer therapeutic response is associated with relatively normal striatal dopamine synthesis capacity but elevated anterior cingulate cortex (ACC) glutamate levels. We sought to test whether these measures can differentiate patients with psychosis who are antipsychotic responsive from those who are antipsychotic nonresponsive in a multicenter cross-sectional study. 1H-magnetic resonance spectroscopy (1H-MRS) was used to measure glutamate levels (Glucorr) in the ACC and in the right striatum in 92 patients across 4 sites (48 responders [R] and 44 nonresponders [NR]). In 54 patients at 2 sites (25 R and 29 NR), we additionally acquired 3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine (18F-DOPA) positron emission tomography (PET) to index striatal dopamine function (Kicer, min-1). The mean ACC Glucorr was higher in the NR than the R group after adjustment for age and sex (F1,80 = 4.27; P = .04). This was associated with an area under the curve for the group discrimination of 0.59. There were no group differences in striatal dopamine function or striatal Glucorr. The results provide partial further support for a role of ACC glutamate, but not striatal dopamine synthesis, in determining the nature of the response to antipsychotic medication. The low discriminative accuracy might be improved in groups with greater clinical separation or increased in future studies that focus on the antipsychotic response at an earlier stage of the disorder and integrate other candidate predictive biomarkers. Greater harmonization of multicenter PET and 1H-MRS may also improve sensitivity., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Introduction: Pandemics are known to affect mental health of the general population and various at-risk groups like healthcare workers, students and people with chronic medical diseases. However, not much is known of the mental health of people with pre-existing mental illness during a pandemic. This systematic review and meta-analysis investigates, whether people with pre-existing mental illness experience an increase in mental health symptoms and experience more hospitalizations during a pandemic., Materials and Methods: A systematic search was conducted in the EMBASE, OVID-MEDLINE and PsycINFO databases to identify potentially eligible studies. Data were extracted independently and continuous data were used in calculating pooled effect sizes of standardized mean difference (SMD) using the random-effects model., Results: Of 1791 records reviewed 15 studies were included. People with pre-existing mental illness have significantly higher psychiatric symptoms, anxiety symptoms and depressive symptoms compared to controls during a pandemic with pooled effect sizes (SMD) of 0.593 (95% confidence interval (CI) 0.46 to 0.72), 0.616 (95% CI 0.49 to 0.73) and 0.597 (95% CI 0.38 to 0.80) respectively. Studies also found a reduction in psychiatric hospitalizations and utilization of psychiatric services during pandemics., Conclusion: The review highlights the need for mental health services to address the increased mental health symptoms in people with pre-existing mental illnesses during a pandemic. Future research should focus on better designed controlled studies of discrete illness groups, so as to provide a robust basis for policy makers to plan appropriate level of support and care for people with mental illness during a pandemic., Competing Interests: The authors declare that they have no competing interests., (© 2020 The Authors.)

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.)

Objective: The study sought to explore to what extent geolocation data has been used to study serious mental illness (SMI). SMIs such as bipolar disorder and schizophrenia are characterized by fluctuating symptoms and sudden relapse. Currently, monitoring of people with an SMI is largely done through face-to-face visits. Smartphone-based geolocation sensors create opportunities for continuous monitoring and early intervention., Materials and Methods: We searched MEDLINE, PsycINFO, and Scopus by combining terms related to geolocation and smartphones with SMI concepts. Study selection and data extraction were done in duplicate., Results: Eighteen publications describing 16 studies were included in our review. Eleven studies focused on bipolar disorder. Common geolocation-derived digital biomarkers were number of locations visited (n = 8), distance traveled (n = 8), time spent at prespecified locations (n = 7), and number of changes in GSM (Global System for Mobile communications) cell (n = 4). Twelve of 14 publications evaluating clinical aspects found an association between geolocation-derived digital biomarker and SMI concepts, especially mood. Geolocation-derived digital biomarkers were more strongly associated with SMI concepts than other information (eg, accelerometer data, smartphone activity, self-reported symptoms). However, small sample sizes and short follow-up warrant cautious interpretation of these findings: of all included studies, 7 had a sample of fewer than 10 patients and 11 had a duration shorter than 12 weeks., Conclusions: The growing body of evidence for the association between SMI concepts and geolocation-derived digital biomarkers shows potential for this instrument to be used for continuous monitoring of patients in their everyday lives, but there is a need for larger studies with longer follow-up times., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Neuroimaging studies in schizophrenia have linked elevated glutamate metabolite levels to non-remission following antipsychotic treatment, and also indicate that antipsychotics can reduce glutamate metabolite levels. However, the relationship between symptomatic reduction and change in glutamate during initial antipsychotic treatment is unclear. Here we report proton magnetic resonance spectroscopy (1H-MRS) measurements of Glx and glutamate in the anterior cingulate cortex (ACC) and thalamus in patients with first episode psychosis (n = 23) at clinical presentation, and after 6 weeks and 9 months of treatment with antipsychotic medication. At 9 months, patients were classified into Remission (n = 12) and Non-Remission (n = 11) subgroups. Healthy volunteers (n = 15) were scanned at the same three time-points. In the thalamus, Glx varied over time according to remission status (P = 0.020). This reflected an increase in Glx between 6 weeks and 9 months in the Non-Remission subgroup that was not evident in the Remission subgroup (P = 0.031). In addition, the change in Glx in the thalamus over the 9 months of treatment was positively correlated with the change in the severity of Positive and Negative Syndrome Scale (PANSS) positive, total and general symptoms (P<0.05). There were no significant effects of group or time on glutamate metabolites in the ACC, and no differences between either patient subgroup and healthy volunteers. These data suggest that the nature of the response to antipsychotic medication may be related to the pattern of changes in glutamatergic metabolite levels over the course of treatment. Specifically, longitudinal reductions in thalamic Glx levels following antipsychotic treatment are associated with symptomatic improvement.

Background: Digital health products designed to help people with severe mental health problems appear to be feasible, acceptable, and efficacious. The challenge facing the digital mental health field is implementing digital tools in routine service delivery. To date, there has been a paucity of qualitative research exploring staff views of digital health solutions in the context of mental healthcare. Engaging and involving frontline staff in the design and rollout of new technology to improve utilization is imperative for successful uptake and adoption of digital tools. The aim of the current study is to explore frontline staff views regarding the utility and appropriateness of using digital tools in the healthcare pathway for people accessing specialist secondary care mental health services. Method: Qualitative study using framework analysis was used with 48 mental health staff working in early intervention for psychosis services. Six groups comprising 5-10 early intervention service staff members in each group were conducted across the Northwest of England. Robust measures were used to develop a stable framework, including member checking, triangulation, and consensus meetings. Results: Three themes were identified a priori : i) perceived barriers to adopting smartphone apps for early psychosis; ii) acceptability of digital health tools for early psychosis patients; and iii) data security, safety, and risk. Alongside exploring the a priori topics, one theme was generated a posteriori : iv) relationships. Conclusions: Staff working in specialist early intervention for psychosis services found digital tools on the whole acceptable in mental health service provision, but raised a number of concerns that will likely affect implementation of such systems into routine service delivery and practice. Thirteen recommendations are made in this paper as a result of the themes generated in these data. Implementing of digital systems needs to be simple and uncomplicated and improve clinical workflows for staff rather than hinder and increase clinical workflows. Furthermore, organizational support with a clear plan for implementing technological innovations is required for successful adoption of digital systems. Consideration of staff views around digital systems is important if successful adoption and implementation of such systems are to occur. Clinical Trial Registration: http://www.isrctn.com, identifier ISRCTN34966555.

Background: The antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved., Methods: In this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I., Findings: Between April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference -0·19, 95% CI -1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group)., Interpretation: Minocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy., Funding: National Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Digital technology has the potential to improve outcomes for people with psychosis. However, to date, research has largely ignored service user views on digital health interventions (DHIs)., Objective: The objective of our study was to explore early psychosis service users' subjective views on DHIs., Methods: Framework analysis was undertaken with data obtained from 21 semistructured interviews with people registered with early intervention for psychosis services. Robust measures were used to develop a stable framework, including member checking, triangulation, independent verification of themes, and consensus meetings., Results: The following 4 themes were established a priori: acceptability of technology in psychosis and mental health; technology increasing access to and augmenting mental health support; barriers to adopting DHIs; and concerns about management of data protection, privacy, risk, and security of information. The following 2 themes were generated a posteriori: blending DHIs with face-to-face treatment and empowerment, control, and choice. DHIs were also viewed as potentially destigmatizing, overcoming barriers faced in traditional service settings, facilitating communication, and empowering service users to take active control of their health care., Conclusions: In the first study of its kind, early psychosis service users' were largely positive about the potential use of DHIs supporting and managing mental health. Overall, service users felt that DHIs were a progressive, modern, and relevant platform for health care delivery. Concerns were expressed around privacy and data security and practical barriers inherent within DHIs, all of which require further attention. Future research should explore whether findings transfer to other service user groups, other technology delivery formats, and across a range of treatment modalities., (©Sandra Bucci, Rohan Morris, Katherine Berry, Natalie Berry, Gillian Haddock, Christine Barrowclough, Shôn Lewis, Dawn Edge. Originally published in JMIR Mental Health (http://mental.jmir.org), 31.10.2018.)

Background: African-Caribbeans in the UK have the highest schizophrenia incidence and greatest inequity in access to mental health services of all ethnic groups. The National Institute for Health and Care Excellence (NICE) highlights this crisis in care and urgent need to improve evidence-based mental healthcare, experiences of services and outcomes for this group. Family intervention (FI) is clinically and cost-effective for the management of schizophrenia but it is rarely offered. Evidence for FI with minority ethnic groups generally, and African-Caribbeans in particular, is lacking. This study aims to test the feasibility and acceptability of delivering Culturally-adapted Family Intervention (CaFI) to African-Caribbean service users diagnosed with schizophrenia., Methods/design: This is a feasibility cohort design study. Over a 12-month intervention period, 30 service users and their families, recruited from hospital and community settings, will receive ten one-hourly sessions of CaFI. Where biological families are absent, access to the intervention will be optimised through 'family support members'; trusted individuals nominated by service users or study volunteers. We shall collect data on eligibility, uptake, retention and attrition and assess the utility and feasibility of collecting various outcome measures including readmission, service engagement, working alliance, clinical symptoms and functioning, perceived criticism, psychosis knowledge, familial stress and economic costs. Measures will be collected at baseline, post-intervention and at 3-month follow-up using validated questionnaires and standardised interviews. Admission rates and change in care management will be rated by independent case note examination. Variability in the measures will inform sample size estimates for a future trial. Independent raters will assess fidelity to the intervention in 10 % of sessions. Feedback at the end of each session along with thematically-analysed qualitative interviews will examine CaFI's acceptability to service users, families and healthcare professionals., Discussion: This innovative response to inequalities in mental healthcare experienced by African-Caribbeans diagnosed with schizophrenia might improve engagement in services, access to evidence-based interventions and clinical outcomes. Successful implementation of CaFI in this group could pave the way for better engagement and provision across marginalised groups and therefore has potentially important implications for commissioning and service delivery in ethnically diverse populations. This study will demonstrate whether the approach is feasible and acceptable and can be implemented with fidelity in different settings.

(Reprinted with permission from Schizophrenia Bulletin 2015; 41(3):549-558)., (Copyright © 2016 by the American Psychiatric Association.)