Shôn Lewis

• BSc MD FMedSci
• Managing Director at The University of Manchester

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 a...

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 wi...

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 unde...

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...

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 ap...

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...

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...

BACKGROUND Psychosis is one of the most disabling mental health conditions and causes significant personal, social and economic burdens. Accurate and timely symptom monitoring is critical in offering prompt and time sensitive clinical services. Digital health is a promising solution for the barriers encountered by conventional symptom monitoring ap...

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...

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...

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...

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. Glutama...

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...

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 discusse...

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 schizophren...

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 sc...

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...

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 p...

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 resist...

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, usabi...

Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remission...

Aims Psychosis is a major mental illness with first onset in young adults. The prognosis is poor in around half of the people affected, and difficult to predict. The few tools available to predict prognosis have major weaknesses which limit their use in clinical practice. We aimed to develop and validate a risk prediction model of symptom non-remis...

Background Patients with a First-Episode of Psychosis (FEP) exhibit low-grade inflammation as demonstrated by elevated levels of C reactive protein (CRP) and pro-inflammatory cytokines. Aims The primary goal of this study was to investigate the association between pro-inflammatory biomarkers and clinical outcomes in unmedicated FEP patients. Meth...

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...

Background: Actissist is a smartphone app designed to deliver an intervention grounded in cognitive behavior therapy for early psychosis. Actissist was developed by a multidisciplinary team of academics, clinicians, experts by experience and software engineers. Actissist has been tested in two trials, the first a proof-of-concept trial where Actiss...

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 metaanalysis investigates,...

Background 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....

Wearable and mobile technology provides new opportunities to manage health conditions remotely and unobtrusively. For example, healthcare providers can repeatedly sample a person's condition to monitor progression of symptoms and intervene if necessary. There is usually a utility-tolerability trade-off between collecting information at sufficient f...

Individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, that may be particularly prominent, already at illness onset, in those more likely to have poorer symptom remission following treatment with the first antipsychotic. The identification of strong neuroanatomical markers of symptom remission could thus f...

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...

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 t...

We discuss the preliminary safety analysis of a smartphone-based intervention for early detection of psychotic relapse. We briefly describe how we identified patient safety hazards associated with the system and how measures were defined to mitigate these hazards.

Background Collecting NHS patient experience data is critical to ensure the delivery of high-quality services. Data are obtained from multiple sources, including service-specific surveys and widely used generic surveys. There are concerns about the timeliness of feedback, that some groups of patients and carers do not give feedback and that free-te...

Background Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of E...

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 t...

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. He...

Cognitive impairment is a major unmet need in the treatment of schizophrenia. Over the last decade, the MATRICS Consensus Cognitive Battery (MCCB) has been used to assess the effects of novel treatments for cognitive impairment in schizophrenia. However, other cognitive-neuroscience-based cognitive batteries, such as the Cambridge Neuropsychologica...

BACKGROUND Improving recovery from acute symptoms and preventing relapse are two major challenges in serious mental illness. We developed a smartphone-based personalised technology to monitor symptoms in real time with good acceptability, reliability and validity. OBJECTIVE To assess (i) acceptability of continuous monitoring to SMI patients and h...

Background: Improving recovery from acute symptoms and preventing relapse are two significant challenges in severe mental illness. We developed a personalized smartphone-based app to monitor symptoms in real time and validated its acceptance, reliability, and validity. Objective: To assess (i) acceptability of continuous monitoring to SMI patien...

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 (...

There is an important gap in scaling up psychosocial interventions for people with severe mental health problems so that these interventions are not only widely available but also delivered in a timely manner. We examined the feasability of adapting a psychological intervention traditionally delivered face-to-face onto a digital platform. We report...

Background In a previous trial we reported that the neuroprotective, anti-inflammatory antibiotic minocycline lessened the negative symptoms of schizophrenia compared with placebo over 1 year. The BeneMin study aimed to replicate this benefit and to determine whether or not there was associated preservation of grey matter, reduction in circulating...

The original Article did not feature the list of collaborators. This has now been corrected in the PDF and HTML versions of this Article.

BACKGROUND Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of E...

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...

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 geolocati...

Background Cognitive impairment is a major unmet need in the treatment of schizophrenia. Over the last decade, the MATRICS Consensus Cognitive Battery (MCCB) and the cognitive-neuroscience-based Cambridge Neuropsychological Test Automated Battery (CANTAB) have been used to assess the effects of novel treatments for cognitive impairment in schizophr...

Background Neuroimaging studies in schizophrenia have linked elevated glutamate metabolite levels to non-remission following antipsychotic treatment and have also indicated that antipsychotics can reduce glutamate metabolite levels. However, the relationship between symptomatic reduction and change in glutamate during initial antipsychotic treatmen...

Background Early response to first-line antipsychotics is associated with positive long-term symptomatic outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are heterogeneous in terms...

Aims Psychotic symptoms fluctuate over time and effective and regular monitoring may contribute to relapse prevention and improve long‐term outcomes. In this proof‐of‐concept study we test the feasibility, acceptability and potential usefulness of a novel digital method assessing the association between physiological signals and psychotic symptom d...

Early response to first-line antipsychotic treatments is strongly associated with positive long-term symptomatic and functional outcome in psychosis. Unfortunately, attempts to identify reliable predictors of treatment response in first-episode psychosis (FEP) patients have not yet been successful. One reason for this could be that FEP patients are...

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 mecha...

Background: No established treatment algorithm exists for patients with schizophrenia. Whether switching antipsychotics or early use of clozapine improves outcome in (first-episode) schizophrenia is unknown. Methods: This three-phase study was done in 27 centres, consisting of general hospitals and psychiatric specialty clinics, in 14 European c...

Objectives To explore service user experiences of a 9-month cognitive behavioural therapy for command hallucinations in the context of a randomised controlled trial including their views on acceptability and tolerability of the intervention. Design Qualitative study using semistructured interviews. Setting The study took place across three sites:...

Background Negative symptoms consist of impaired quality of life, social isolation, reduced emotional responsiveness, self-neglect and anhedonia, which have been categorised into avolition-apathy and expressive deficits sub-domains. The treatment of negative symptoms remains a challenge. Depression is commonly seen in schizophrenia and previous fin...

Background We developed a smartphone-based personalised technology to monitor symptoms in real time and showed good acceptability, reliability and validity for active remote monitoring of symptoms in previous published studies (www.clintouch.com). We report a randomised trial testing its efficacy in improving psychotic symptom control, and its pote...

Background We hypothesised that a multi-modal psychosocial intervention (PSI) after first episodes of non-affective psychosis would increase antipsychotic adherence, improve functioning and prevent readmission in a multi-centre, blind-rated, randomised controlled trial. Methods Following treatment of first episode non-affective psychosis with amis...

Background Depending on the nature of their items factor analyses of different scales impose different structures on the underlying psychopathological dimensions, so a broader range of scale items should be more revealing. Few studies repeat analyses over successive interviews to investigate whether psychopathology has a consistent structure or evo...

Background Variable outcomes following a first-episode of psychosis are partly attributable to heterogeneity in cognitive functioning. Previous work in first episode psychosis has identified clinically meaningful cognitive sub-types based on pre-specified differences in estimated premorbid and current cognitive functioning. We used an empirical clu...

Background: Timely access to intervention for psychosis is crucial yet problematic. As such, health care providers are forming digital strategies for addressing mental health challenges. A theory-driven digital intervention that monitors distressing experiences and provides real-time active management strategies could improve the speed and quality...

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 underta...

Background Acting on harmful command hallucinations is a major clinical concern. Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR = 0.45, 95% CI 0.23–0.88, p = 0.021). The focus of the therapy was a single mechanism, the power dimension of voice appraisal, was also significantly reduced. We hypothesised that voice power...

Background: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or...

Background: The negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation and socialization that tend to be persistent despite standard antipsychotic treatment. Two sub-domains of expressive deficits (affective flattening and poverty of speech) and avolition-amotivation for daily-life and social activities (a...

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 outcom...

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...

Background:Most of the 13 542 trials contained in the Cochrane Schizophrenia Group’s register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered. For exampl...

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De-identified trial data. (DTA)

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Background: Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence...

Objective: Male gender and young age at onset of schizophrenia are traditionally associated with poor treatment outcome and often used to determine prognosis. However, many studies use nonincident samples and fail to adjust for symptom severity at onset. We hypothesized that age and gender would influence severity of presentation but would not pre...

Few studies have examined therapist effects and therapeutic alliance (TA) in treatments for chronic fatigue syndrome (CFS). Therapist effects are the differences in outcomes achieved by different therapists. TA is the quality of the bond and level of agreement regarding the goals and tasks of therapy. Prior research suffers the methodological probl...

Univariate correlations between therapeutic alliance and changes in fatigue and physical functioning by therapy and therapist. (DOCX)

Mental and brain disorders represent the greatest health burden to Europe—not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European devel...

Background: Cognitive behaviour therapy (CBT) is recommended for the treatment of psychosis; however, only a small proportion of service users have access to this intervention. Smartphone technology using software applications (apps) could increase access to psychological approaches for psychosis. This paper reports the protocol development for a...

Current approaches to the management of severe mental illness have four major limitations: 1) symptom reporting is intermittent and subject to problems with reliability; 2) service users report feelings of disengagement from their care planning; 3) late detection of symptoms delay interventions and increase the risk of relapse; and 4) care systems...

Paranoia is one of the commonest symptoms of psychosis but has rarely been studied in a population at risk of developing psychosis. Based on existing theoretical models, including the proposed distinction between 'poor me' and 'bad me' paranoia, we aimed to test specific predictions about associations between negative cognition, metacognitive belie...

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...

Digital technology has the potential to transform mental healthcare by connecting patients, services and health data in new ways. Digital online and mobile applications can offer patients greater access to information and services and enhance clinical management and early intervention through access to real-time patient data. However, substantial g...

Several efforts to develop pharmacological treatments with a beneficial effect on cognition in schizophrenia are underway, while cognitive remediation has shown modest effects on cognitive performance. Our goal was to test if pharmacological augmentation of cognitive training would result in enhancement of training-induced learning. We chose modafi...