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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., Competing Interests: Declaration of competing interest Bucci, Ainsworth and Lewis are Directors and shareholders of CareLoop Health Ltd, which develops and markets digital therapeutics for schizophrenia and a digital screening app for postnatal depression. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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.)

Glutamate and increased inflammation have been separately implicated in the pathophysiology of schizophrenia and the extent of clinical response to antipsychotic treatment. Despite the mechanistic links between pro-inflammatory and glutamatergic pathways, the relationships between peripheral inflammatory markers and brain glutamate in schizophrenia have not yet been investigated. In this study, we tested the hypothesis that peripheral levels of pro-inflammatory cytokines would be positively associated with brain glutamate levels in schizophrenia. Secondary analyses determined whether this relationship differed according to antipsychotic treatment response. The sample consisted of 79 patients with schizophrenia, of whom 40 were rated as antipsychotic responders and 39 as antipsychotic non-responders. Brain glutamate levels were assessed in the anterior cingulate cortex (ACC) and caudate using proton magnetic resonance spectroscopy ( 1 H-MRS) and blood samples were collected for cytokine assay on the same study visit (IL-6, IL-8, IL-10, TNF- α and IFN-γ). Across the whole patient sample, there was a positive relationship between interferon-gamma (IFN-γ) and caudate glutamate levels (r = 0.31, p = 0.02). In the antipsychotic non-responsive group only, there was a positive relationship between interleukin-8 (IL-8) and caudate glutamate (r = 0.46, p = 0.01). These findings provide evidence to link specific peripheral inflammatory markers and caudate glutamate in schizophrenia and may suggest that this relationship is most marked in patients who show a poor response to antipsychotic treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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

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: 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.)

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., Competing Interests: Declaration of competing interest VM has received research funding from Johnson & Johnson as part of a research program on depression and inflammation. BD has share options in P1vital and has received consultancy fees from Autifony.com. BPM has provided advice on complement to Roche and is a consultant to GlaxoSmithKline; all fees were paid to Cardiff University. JW reported receiving a grant from Takeda Pharmaceuticals outside of the submitted work. In the past three years, SML has received funding for research from Janssen, and personal fees for participating in educational meetings from Janssen and Sunovion. The remaining authors report no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

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.)

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. 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., Methods: 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., Results: 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., Discussion: 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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.)

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 suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions., Objective: To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia., Design: A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up., Setting: Adult psychiatric services, treating people with schizophrenia., Participants: Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity., Interventions: Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study., Main Outcome Measures: The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale., Results: No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation., Limitations: The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited., Conclusion: Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies., Future Work: Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge., Trial Registration: European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2009-009235-30 and Current Controlled Trials ISRCTN42305247., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 29. See the NIHR Journals Library website for further project information.

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 predict outcome after adjustment for symptoms at presentation., Method: 628 people with first-episode ICD-9 and DSM-IV nonaffective psychosis from 2 historical cohorts recruited from sequential presentations in Canada and the United Kingdom (1996-1998) were assessed prospectively at presentation and over 12-18 months using the Positive and Negative Syndrome Scale (PANSS)., Results: Models of the age-at-onset distributions with 2 underlying modes at similar ages in women (ages 23 years and 47 years) and men (ages 22 years and 46 years) had relatively good fits compared to single-mode models (χ(2)1 better by 9.2 for females, 8.0 for males, both P < .05). At presentation, scores for negative symptoms were 1.84 points worse for males (95% CI, 1.05 to 2.58; P < .001) in a mixed effects model. Younger age also predicted higher negative scores at presentation (partial correlation r = -0.18, P < .01; P < .001 in the mixed effects model). Findings were similar for cognitive-disorganized symptoms. However, after controlling for baseline symptoms, age at onset and gender did not significantly predict subsequent symptom course in the mixed effects models., Conclusions: Gender and age at onset are independently associated with symptoms at presentation but not with medium-term course of schizophrenia. This finding reinforces the importance of early identification and prevention of severe negative symptoms at first episode, whatever an individual's age and gender., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

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.

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., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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

Background: 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 example, when a first antipsychotic failed, is switching to another drug effective? And when should we use clozapine? The aim of this article is to review the efficacy of switching antipsychotics in case of nonresponse. We also present the European Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia., Methods: We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial., Results: We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode patients are treated with amisulpride for 4 weeks, followed by a 6-week double-blind RCT comparing continuation of amisulpride with switching to olanzapine and ultimately a 12-week clozapine treatment in nonremitters. A subsequent 1-year RCT validates psychosocial interventions to enhance adherence., Discussion: Current literature fails to provide basic guidance for the pharmacological treatment of schizophrenia. The OPTiMiSE trial is expected to provide a basis for clinical guidelines to treat patients with a first episode of schizophrenia., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© 2013 Published by Elsevier Ireland Ltd.)

Background: It is uncertain whether antipsychotic long-acting injection (LAI) medication in schizophrenia is associated with better clinical outcomes than oral preparations., Aims: To examine the impact of prior treatment delivery route on treatment outcomes and whether any differences are moderated by adherence., Method: Analysis of data from two pragmatic 1-year clinical trials in which patients with schizophrenia were randomised to either an oral first-generation antipsychotic (FGA), or a non-clozapine second-generation antipsychotic (SGA, CUtLASS 1 study), or a non-clozapine SGA or clozapine (CUtLASS 2 study)., Results: Across both trials, 43% (n = 155) of participants were prescribed an FGA-LAI before randomisation. At 1-year follow-up they showed less improvement in quality of life, symptoms and global functioning than those randomised from oral medication. This difference was confined to patients rated as less than consistently adherent pre-randomisation. The relatively poor improvement in the patients prescribed an LAI pre-randomisation was ameliorated if they had been randomised to clozapine rather than another SGA. There was no advantage to being randomly assigned from an LAI at baseline to a non-clozapine oral SGA rather than an oral FGA., Conclusions: A switch at randomisation from an LAI to an oral antipsychotic was associated with poorer clinical and functional outcomes at 1-year follow-up compared with switching from one oral antipsychotic to another. This effect appears to be moderated by adherence, and may not extend to switching to clozapine. This has implications for clinical trial design: the drug from which a participant is randomised may have a greater effect than the drug to which they are randomised.

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

Background: Interventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed., Aims: To document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway., Method: Data for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed., Results: A third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP., Conclusions: Community education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.

The impact of non-neurological and metabolic side effects (NNSEs) on the prescription of antipsychotics in real clinical practice remains unclear. We conducted an intention-to-treat, secondary analysis of data from a randomised, controlled trial (CUtLASS-1; n=227) to examine NNSEs emergent at 12 weeks and 52 weeks. A clinically significant difference was defined as double or half the symptoms in groups prescribed first- versus second-generation antipsychotics, represented by odds ratios greater than 2.0 (indicating advantage for first-generation drugs) or less than 0.5 (indicating advantage for the newer drugs). There were no differences between the treatment groups at baseline. At both 12 and 52 weeks follow-up, patients on second-generation drugs were more likely than their first-generation counterparts to experience cardiovascular problems and anticholinergic side effects, as well as increased sexual side effects in men. Objective weight gain was equivalent between the two groups at 12 weeks, but by one year fewer patients in the second-generation arm experienced weight gain and there was no significant difference with regard to percent change in BMI. These results suggest that there may be clinically significant increases in anticholinergic, cardiovascular, and sexual side effects for patients on second-generation drugs. The expected increased weight gain in the second-generation arm did not occur. This study provides evidence that clinicians should take a more nuanced approach toward expert antipsychotic prescription, rather than viewing the drugs as distinct classes., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Over the past decade policy makers have emphasised the importance of healthcare technology in the management of long-term conditions. Mobile-phone based assessment may be one method of facilitating clinically- and cost-effective intervention, and increasing the autonomy and independence of service users. Recently, text-message and smartphone interfaces have been developed for the real-time assessment of symptoms in individuals with schizophrenia. Little is currently understood about patients' perceptions of these systems, and how they might be implemented into their everyday routine and clinical care., Method: 24 community based individuals with non-affective psychosis completed a randomised repeated-measure cross-over design study, where they filled in self-report questions about their symptoms via text-messages on their own phone, or via a purpose designed software application for Android smartphones, for six days. Qualitative interviews were conducted in order to explore participants' perceptions and experiences of the devices, and thematic analysis was used to analyse the data., Results: Three themes emerged from the data: i) the appeal of usability and familiarity, ii) acceptability, validity and integration into domestic routines, and iii) perceived impact on clinical care. Although participants generally found the technology non-stigmatising and well integrated into their everyday activities, the repetitiveness of the questions was identified as a likely barrier to long-term adoption. Potential benefits to the quality of care received were seen in terms of assisting clinicians, faster and more efficient data exchange, and aiding patient-clinician communication. However, patients often failed to see the relevance of the systems to their personal situations, and emphasised the threat to the person centred element of their care., Conclusions: The feedback presented in this paper suggests that patients are conscious of the benefits that mobile-phone based assessment could bring to clinical care, and that the technology can be successfully integrated into everyday routine. However, it also suggests that it is important to demonstrate to patients the personal, as well as theoretical, benefits of the technology. In the future it will be important to establish whether clinical practitioners are able to use this technology as part of a personalised mental health regime.

Objectives: The aim of the study was to investigate sexual function in patients with schizophrenia receiving treatment with a first-generation antipsychotic (FGA) or a second-generation antipsychotic (SGA) drug. Sexual function is an important aspect of human experience, which can be affected by antipsychotic drug treatment. Sexual dysfunction in patients with schizophrenia may be less prevalent with SGA than with FGA drug treatment., Methods: A cross-sectional prevalence study assessed sexual function in a sample of 144 patients with DSM-IV schizophrenia aged between 18 and 65, using the Derogatis Interview for Sexual Functioning (self-report version: DISF-SR). Two equal-sized groups (N = 72) received treatment with an FGA or an SGA drug for at least 12 weeks., Results: No significant differences were seen on DISF-SR total score or subscale score between the two treatment groups., Conclusions: There are no differences in measured sexual function of non-randomised patients with schizophrenia treated with an FGA compared with SGA-treated patients.

There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis. A randomized controlled trial compared cognitive therapy (CT) over 6 months with monthly monitoring in 58 patients meeting criteria for ultrahigh risk of developing a first episode of psychosis. Participants were followed up over a 3-year period. Logistic regression demonstrated that CT significantly reduced likelihood of being prescribed antipsychotic medication over a 3-year period, but it did not affect transition to psychosis defined using the Positive and Negative Syndrome Scale (PANSS) or probable Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis. However, exploratory analyses revealed that CT significantly reduced the likelihood of making progression to psychosis as defined on the PANSS over 3 years after controlling for baseline cognitive factors. Follow-up rate at 3 years was 47%. There appear to be enduring benefits of CT over the long term, suggesting that it is an efficacious intervention for people at high risk of developing psychosis.

The aim of this study was to investigate the reliability, validity and structure of the Psychotic Symptom Rating Scales (PSYRATS) in 257 subjects presenting with acute first episodes of schizophrenia or related disorders. The PSYRATS have been shown to assess dimensions of hallucination and delusions reliably and validly in chronically psychotic patients but not in first episode patients. Item reliability was investigated and subscale performance compared to the PANSS. The PSYRATS had good inter-rater and retest reliability. Validity was good, as assessed by internal consistency, sensitivity to change, and in relation to the PANSS. There was evidence of two delusion factors and three for hallucinations. The scales are useful complements to existing measures of symptom severity.

Objective: To estimate the effect of insight on time to relapse and readmission and on social function and symptoms after following up a cohort of first-episodes of nonaffective psychosis for 18 months., Method: Patients with first episodes of DSM-IV schizophreniform disorder, schizophrenia, schizoaffective disorder, delusional disorder, and psychosis not otherwise specified (excluding primary substance-induced or organic psychoses), aged 16 to 65 years, were recruited over the 26 months from July 1996 to September 1998 from consecutive admissions to day-patient and inpatient units in England with a catchment area population of 2.3 million. They were interviewed with the Positive and Negative Syndrome Scale, Birchwood Insight Scale, and Social Functioning Scale at baseline and 18 months., Results: The hazard ratio for relapse, per unit increase in the insight score, was estimated in a Cox proportional hazards model to be 0.943 (95% CI = 0.892 to 0.996; p = .035). Those with the best insight scores had an estimated rate of relapse that was 39% of that of those with the worst scores (95% CI = 16% to 93%). Readmission was highly correlated with relapse, so poor insight also predicted readmission (hazard ratio 0.934; 95% CI = 0.876 to 0.996; p = .036). However, insight did not independently predict symptoms or social function after adjustment for other predictors of outcome., Conclusion: Insight predicted both relapse and readmission. The details of the beliefs and assumptions determining outcome remain unclear, but intervening to alter them appears to be justified.

Context: Second-generation (atypical) antipsychotics (SGAs) are more expensive than first-generation (typical) antipsychotics (FGAs) but are perceived to be more effective, with fewer adverse effects, and preferable to patients. Most evidence comes from short-term efficacy trials of symptoms., Objective: To test the hypothesis that in people with schizophrenia requiring a change in treatment, SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs., Design: A noncommercially funded, pragmatic, multisite, randomized controlled trial of antipsychotic drug classes, with blind assessments at 12, 26, and 56 weeks using intention-to-treat analysis., Setting: Fourteen community psychiatric services in the English National Health Service., Participants: Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects., Interventions: Randomized prescription of either FGAs or SGAs (other than clozapine), with the choice of individual drug made by the managing psychiatrist., Main Outcome Measures: Quality of Life Scale scores, symptoms, adverse effects, participant satisfaction, and costs of care., Results: The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded. Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores. Participants reported no clear preference for either drug group; costs were similar., Conclusions: In people with schizophrenia whose medication is changed for clinical reasons, there is no disadvantage across 1 year in terms of quality of life, symptoms, or associated costs of care in using FGAs rather than nonclozapine SGAs. Neither inadequate power nor patterns of drug discontinuation accounted for the result.

There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia. It is less clear if clozapine is more effective than the other second-generation antipsychotic (SGA) drugs. A noncommercially funded, pragmatic, open, multisite, randomized controlled trial was conducted in the United Kingdom National Health Service (NHS). Participants were 136 people aged 18-65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs. Participants were randomly allocated to clozapine or to one of the class of other SGA drugs (risperidone, olanzapine, quetiapine, amisulpride) as selected by the managing clinician. Outcomes were assessed blind to treatment allocation. One-year assessments were carried out in 87% of the sample. The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score (3.63 points; CI: 0.46-7.71; p = .08) but did show an advantage in Positive and Negative Syndrome Scale (PANSS) total score that was statistically significant (-4.93 points; CI: -8.82 to -1.05; p = .013) during follow-up. Clozapine showed a trend toward having fewer total extrapyramidal side effects. At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs. In conclusion, in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs, there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year.

There is a range of psychological interventions for established schizophrenia. These include family interventions, motivational interventions for substance misuse and for non-adherence to medication, cognitive remediation for neurocognitive deficits and cognitive-behavioural therapy for symptoms. Psychological interventions may explicitly target risk factors for poor outcome, such as substance use, or protective factors, such as adherence to medication, or be directed at specific symptoms or deficits. There is emerging evidence for efficacy of psychological treatments during, following and even prior to the first episode. Important areas for further study are how different treatment modalities can interact productively, and patient and carer preferences for treatment. Many trials of psychological treatments have design flaws and this tends to overestimate the treatment effect.

The effectiveness of psychological treatments in schizophrenia has been explored in controlled trials over the last 15 years leading to the conclusion that they are an important adjunct to antipsychotic medication in the treatment of the disorder. Family interventions and cognitive-behavioral treatments have received the most attention. However, studies have mainly been carried out with individuals with chronic, treatment-resistant psychosis, where participants have already been stabilized on antipsychotic medication, and there has been little evaluation of approaches with people with a first episode of schizophrenia. This article will review the literature relating to cognitive-behavioral individual and family interventions in early psychosis. The little evidence that exists suggests that family interventions and individual cognitive-behavioral interventions are acceptable to first-episode patients and that patients can be retained in treatment. In addition, some studies suggest that psychological treatments convey advantages over standard treatments for psychosis in terms of reducing the transition from pre-psychotic states to full-blown psychosis, reducing residual psychotic symptomatology, and improving caregiver outcomes. Considerable work is needed to elucidate the specific needs of first-episode patients and to rigorously evaluate the effectiveness of psychological interventions. The challenges to be met in developing treatments in this area relate to addressing the developmental needs of this group, incorporating substance use routinely into interventions, and developing treatments that are specific to the phase of illness that the individuals are experiencing.

Background: Early intervention teams attempt to improve outcome in schizophrenia through earlier detection and the provision of phase-specific treatments. Whilst the number of early intervention teams is growing, there is a lack of clarity over their essential structural and functional elements., Methods: A 'Delphi' exercise was carried out to identify how far there was consensus on the essential elements of early intervention teams in a group of 21 UK expert clinicians. Using published guidelines, an initial list was constructed containing 151 elements from ten categories of team structure and function., Results: Overall there was expert consensus on the importance of 136 (90%) of these elements. Of the items on which there was consensus, 106 (70.2%) were rated essential, meaning that in their absence the functioning of the team would be severely impaired., Conclusion: This degree of consensus over essential elements suggests that it is reasonable to define a model for UK early intervention teams, from which a measure of fidelity could be derived.

Background: The initial phase of a trial of cognitive-behavioural therapy (CBT) for acutely ill patients with schizophrenia of recent onset showed that it speeded recovery., Aims: To test the hypothesis that CBT in addition to treatment as usual (TAU) during the first or second acute episode of schizophrenia will confer clinical benefit over a follow-up period., Method: This was an 18-month follow-up of a multicentre prospective trial of CBT or supportive counselling administered as an adjunct to TAU, compared with TAU alone, for patients hospitalised for an acute episode of schizophrenia of recent onset. Primary outcomes were total and positive symptom scales, time to relapse and re-hospitalisation., Results: There were significant advantages for CBT and supportive counselling over TAU alone on symptom measures at 18 months but no group difference was seen for relapse or re-hospitalisation. There was a significant centre-treatment interaction, reflecting centre differences in the effect of introducing either treatment, but not in the comparison of CBT and supportive counselling. Medication dosage and compliance did not explain group differences., Conclusions: Adjunctive psychological treatments can have a beneficial long-term effect on symptom reduction.

Background: Comorbid substance misuse in people with schizophrenia is associated with poor clinical and social outcomes. There are few studies of psychological treatments for this population and little long-term follow-up of their benefits., Aims: To investigate symptom, substance use, functioning and health economy outcomes for patients with schizophrenia and their carers 18 months after a cognitive-behavioural treatment (CBT) programme., Method: Patients with dual diagnosis from a randomised controlled trial of motivational intervention, individual CBT and family intervention were assessed on multiple outcomes at 18-month follow-up. Carers were assessed on symptom, functioning and needs over 12 months. Health economy data were collected over 18 months., Results: There were significant improvements in patient functioning compared with routine care over 18 months. No significant differences between treatment groups were found in carer or cost outcomes., Conclusions: The treatment programme was superior to routine care on outcomes relating to illness and service use, and the cost was comparable to the control treatment.

The relationship between neurocognitive impairments in schizophrenia remains unclear. Recent literature was reviewed and the most consistent finding was an association between perseverative errors on the Wisconsin Card Sort Test (WCST) and poor insight. The aim was to confirm and extend this finding using a range of assessments relevant to perseveration, and different dimensions of insight, in a sample of 33 acutely psychotic subjects within 5 years of onset of schizophrenia and related disorders. Results showed a correlation (r=-0.59) between insight and perseverative errors, rather than more general measures of abstraction. A factor representing relabelling symptoms, derived from insight scale items, correlated even more strongly; however, other insight factors correlated more weakly, suggesting they are less dependent on neuropsychological deficits. The ability to monitor output and correct errors appears to be closely related to the core features of insight in psychosis.

There remains disagreement over whether increased risk of schizotypal personality disorder (SPD) is confined to the relatives of patients with a diagnosis of schizophrenia or whether it is a more general characteristic of the relatives of all psychotic patients. To examine the relationship between schizotypal dimensions in relatives and psychopathological syndromes in patients with functional psychoses, factor analysis was carried out on (1) ratings from Present State Examination (PSE) interviews with 172 consecutively admitted patients with psychosis (52% of them with schizophrenia), and (2) ratings on items from three schizotypal scales concerning 263 of their nonpsychotic first degree relatives. The factors derived from the patients' PSE interviews were correlated with the schizotypal factors and the nine DSM-IV criteria for SPD concerning the relatives and subjected to a canonical correlation analysis. In this study, no differences were observed concerning the distribution of schizotypal factors or DSM-IV schizotypal features in the relatives of patients with different psychotic diagnoses. However, a syndrome characterized by delusions, hallucinations, and thought interference (positive symptoms) in patients was correlated with high scores on the three schizotypy scales and with positive and negative schizotypal features in relatives.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Semi-structured interview scales for psychosis are the gold standard approach to assessing psychotic and other symptoms. However, such assessments have limitations such as recall bias, averaging, insensitivity to change and variable interrater reliability. Ambulant, real-time self-report assessment devices may hold advantages over interview measures, but it needs to be shown that the data thus collected are valid, and the collection method is acceptable, feasible and safe. We report on a monitoring system for the assessment of psychosis using smartphone technology. The primary aims were to: i) assess validity through correlations of item responses with those on widely accepted interview assessments of psychosis, and ii) examine compliance to the procedure in individuals with psychosis of varying severity. Methods A total of 44 participants (acute or remitted DSM-4 schizophrenia and related disorders, and prodromal) completed 14 branching self-report items concerning key psychotic symptoms on a touch-screen mobile phone when prompted by an alarm at six pseudo-random times, each day, for one week. Face to face PANSS and CDS interviews were conducted before and after the assessment period blind to the ambulant data. Results Compliance as defined by completion of at least 33% of all possible data-points over seven days was 82%. In the 36 compliant participants, 5 items (delusions, hallucinations, suspiciousness, anxiety, hopelessness) showed moderate to strong (rho 0.6-0.8) associations with corresponding items from interview rating scales. Four items showed no significant correlation with rating scales: each was an item based on observable behaviour. Ambulant ratings showed excellent test-retest reliability and sensitivity to change. Conclusions Ambulatory monitoring of symptoms several times daily using smartphone software applications represents a feasible and valid way of assessing psychotic phenomena for research and clinical management purposes. Further evaluation required over longer assessment periods, in clinical trials and service settings.

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]