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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.

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.

This is the authors' accepted manuscript of an article published in Psychological Medicine., Background: 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 test specific predictions about associations between negative cognition, metacognitive beliefs and negative emotions and paranoid ideation and the belief that persecution is deserved (deservedness). Methods: We used data from 117 participants from the EDIE-2 trial of cognitive behaviour therapy for people at high risk of developing psychosis, comparing them with samples of psychiatric inpatients and healthy students from a previous study. Multi-level modelling was utilised to examine predictors of both paranoia and deservedness, with post-hoc planned comparisons conducted to test whether person-level predictor variables were associated differentially with paranoia or with deservedness. Results: Our sample of ARMS participants was not as paranoid, but reported higher levels of “bad-me” deservedness, compared to psychiatric inpatients. We found several predictors of paranoia and deservedness. Negative beliefs about self were related to deservedness but not paranoia, whereas negative beliefs about others were positively related to paranoia but negatively with deservedness. Both depression and negative metacognitive beliefs about paranoid thinking were specifically related to paranoia but not deservedness. Conclusions: This study provides evidence for the role of negative cognition, metacognition and negative affect in the development of paranoid beliefs, which has implications for psychological interventions and our understanding of psychosis.

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health. Thus, there clearly is a pressing need for defining biomarkers that may be helpful to predict response to treatment and sensitivity to side effects in first-episode psychosis. The present systematic review provides (1) trials that assessed biological markers associated with antipsychotic response or side effects in first-episode psychosis and (2) potential biomarkers associated with biological disturbances that may guide the choice of conventional treatments or the prescription of innovative treatments. Trials including first-episode psychoses are few in number. Most of the available data focused on pharmacogenetics markers with so far only preliminary results. To date, these studies yielded-beside markers for metabolism of antipsychotics-no or only a few biomarkers for response or side effects, none of which have been implemented in daily clinical practice. Other biomarkers exploring immunoinflammatory, oxidative, and hormonal disturbances emerged as biomarkers of first-episode psychoses in the last decades, and some of them have been associated with treatment response. In addition to pharmacogenetics, further efforts should focus on the association of emergent biomarkers with conventional treatments or with innovative therapies efficacy, where some preliminary data suggest promising results.

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.

BACKGROUND: The nosological status of auditory hallucinations in non-clinical samples is unclear. AIMS: To investigate the functional neural basis of non-clinical hallucinations. METHOD: After selection from 1206 people, 68 participants of high, medium and low hallucination proneness completed a task designed to elicit verbal hallucinatory phenomena under conditions of stimulus degradation. Eight subjects who reported hearing a voice when none was present repeated the task during functional imaging. RESULTS: During the signal detection task, the high hallucination-prone participants reported a voice to be present when it was not (false alarms) significantly more often than the average or low participants (P<0.03, d.f.=2). On functional magnetic resonance imaging, patterns of activation during these false alarms showed activation in the superior and middle temporal cortex (P<0.001). CONCLUSIONS: Auditory hallucinatory experiences reported in non-clinical samples appear to be mediated by similar patterns of cerebral activation as found during hallucinations in schizophrenia.

Objective: Recent studies have suggested that cannabis use is a risk factor for developing schizophrenia. We tested the hypothesis that cannabis use increases the likelihood of psychosis-like experiences in non-clinical participants who scored highly on a measure of schizotypy. Method: The psychological effects of cannabis were assessed in 137 healthy individuals (76% female, mean age 22 years) using a newly developed questionnaire concerned with subjective experiences of the drug: the Cannabis Experiences Questionnaire. The questionnaire has three subscales: Pleasurable Experiences, Psychosis-Like Experiences and After-Effects. Respondents also completed the brief Schizotypal Personality Questionnaire. Results: Cannabis use was reported by 72% of the sample. Use per se was not significantly related to schizotypy. However, high scoring schizotypes were more likely to report both psychosis-like experiences and unpleasant after-effects associated with cannabis use. The pleasurable effects of cannabis use were not related to schizotypy score. Conclusion: High scoring schizotypes who use cannabis are more likely to experience psychosis-like phenomena at the time of use, and unpleasant after-effects. Our results are consistent with the hypothesis that cannabis use is a risk factor for full psychosis in this group. Copyright (c) 2006 S. Karger AG, Basel.

Neurological soft signs have been observed in patients with schizophrenia and their relatives. However, it has not been considered whether the increased rates of neurological soft signs are related to measures of psychosis proneness in the general population. We tested this hypothesis in a group of normal volunteers (n = 28) who scored highly for positive schizotypy when assessed online and a control group (n = 33) who scored below the mean. Compared with the controls, high psychosis-prone individuals showed significantly higher Total and Other Soft Signs subscale scores on the Neurological Evaluation Scale. It appears that soft signs are also associated with psychosis proneness when measured in the general population, which suggests that soft signs are distributed along a continuum of risk for schizophrenia.

The natural history of neurocognition in schizophrenia is unclear, with great uncertainty over whether the common baseline, characterised by a range of functional and neurocognitive deficits reported in subjects with, and at risk of, schizophrenia can provide any prediction as to patient outlook and outcome. Several recent follow-up studies have tracked 'change' in neurocognition over time (Censits et al, 1997; Heaton et al, 2001; Hughes et al, 2002). Studies restricted to first episode cases (Nopoulos et al, 1994; Gold et al 1999; Townsend et al, 2002) have yielded equivocal findings, with some authors reporting no overall pattern of change (see Rund's meta-analysis: Rund, 1998) and others reporting modest and/or selective improvement over time (Hoff et al, 1999; Townsend et al, 2002). Unfortunately, first-episode studies have, for the most part, been limited by the relatively short duration of follow-up (often less than 24 months) and/or significant sample attrition.

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 gaps exist in the evidence base underlying these technologies. Greater patient and clinician involvement is needed to evaluate digital technologies and ensure they target unmet needs, maintain public trust and improve clinical outcomes.

Background Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer’s motivation to comply. Methods In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. Findings 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23–0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40–1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33–0·98, p=0·042). Interpretation This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and co

Background Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer’s motivation to comply. Methods In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. Findings 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23–0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40–1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33–0·98, p=0·042). Interpretation This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and co

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 gaps exist in the evidence base underlying these technologies. Greater patient and clinician involvement is needed to evaluate digital technologies and ensure they target unmet needs, maintain public trust and improve clinical outcomes.

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 development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society. Here, we describe a comprehensive, coordinated mental health research agenda for Europe and worldwide. This agenda was based on systematic reviews of published work and consensus decision making by multidisciplinary scientific experts and affected stakeholders (more than 1000 in total): individuals with mental health problems and their families, health-care workers, policy makers, and funders. We generated six priorities that will, over the next 5–10 years, help to close the biggest gaps in mental health research in Europe, and in turn overcome the substantial challenges caused by mental disorders.

Background Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer’s motivation to comply. Methods In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. Findings 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23–0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40–1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33–0·98, p=0·042). Interpretation This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and co

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 gaps exist in the evidence base underlying these technologies. Greater patient and clinician involvement is needed to evaluate digital technologies and ensure they target unmet needs, maintain public trust and improve clinical outcomes.

Background Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer’s motivation to comply. Methods In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. Findings 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23–0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40–1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33–0·98, p=0·042). Interpretation This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and co

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 gaps exist in the evidence base underlying these technologies. Greater patient and clinician involvement is needed to evaluate digital technologies and ensure they target unmet needs, maintain public trust and improve clinical outcomes.

Background Acting on command hallucinations in psychosis can have serious consequences for the individual and for other people and is a major cause of clinical and public concern. No evidence-based treatments are available to reduce this risk behaviour. We therefore tested our new cognitive therapy to challenge the perceived power of voices to inflict harm on the voice hearer if commands are not followed, thereby reducing the hearer’s motivation to comply. Methods In COMMAND, a single-blind, randomised controlled trial, eligible participants from three centres in the UK who had command hallucinations for at least 6 months leading to major episodes of harm to themselves or other people were assigned in a 1: 1 ratio to cognitive therapy for command hallucinations + treatment as usual versus just treatment as usual for 9 months. Only the raters were masked to treatment assignment. The primary outcome was harmful compliance. Analysis was by intention to treat. The trial is registered, number ISRCTN62304114. Findings 98 (50%) of 197 participants were assigned to cognitive therapy for command hallucinations + treatment as usual and 99 (50%) to treatment as usual. At 18 months, 39 (46%) of 85 participants in the treatment as usual group fully complied with the voices compared with 22 (28%) of 79 in the cognitive therapy for command hallucinations + treatment as usual group (odds ratio 0·45, 95% CI 0·23–0·88, p=0·021). At 9 months the treatment effect was not significant (0·74, 0·40–1·39, p=0·353). However, the treatment by follow-up interaction was not significant and the treatment effect common to both follow-up points was 0·57 (0·33–0·98, p=0·042). Interpretation This is the first trial to show a clinically meaningful reduction in risk behaviour associated with commanding voices. We will next determine if change in power was the mediator of change. Further more complex trials are needed to identify the most influential components of the treatment in reducing power and co

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 gaps exist in the evidence base underlying these technologies. Greater patient and clinician involvement is needed to evaluate digital technologies and ensure they target unmet needs, maintain public trust and improve clinical outcomes.