Characterising cognitive heterogeneity in individuals at clinical high-risk for psychosis: a cluster analysis with clinical and functional outcome prediction.

Schizophrenia is characterised by cognitive impairments that are already present during early stages, including in the clinical high-risk for psychosis (CHR-P) state and first-episode psychosis (FEP). Moreover, data suggest the presence of distinct cognitive subtypes during early-stage psychosis, with evidence for spared vs. impaired cognitive profiles that may be differentially associated with symptomatic and functional outcomes. Using cluster analysis, we sought to determine whether cognitive subgroups were associated with clinical and functional outcomes in CHR-P individuals. Data were available for 146 CHR-P participants of whom 122 completed a 6- and/or 12-month follow-up; 15 FEP participants; 47 participants not fulfilling CHR-P criteria (CHR-Ns); and 53 healthy controls (HCs). We performed hierarchical cluster analysis on principal components derived from neurocognitive and social cognitive measures. Within the CHR-P group, clusters were compared on clinical and functional variables and examined for associations with global functioning, persistent attenuated psychotic symptoms and transition to psychosis. Two discrete cognitive subgroups emerged across all participants: 45.9% of CHR-P individuals were cognitively impaired compared to 93.3% of FEP, 29.8% of CHR-N and 30.2% of HC participants. Cognitively impaired CHR-P participants also had significantly poorer functioning at baseline and follow-up than their cognitively spared counterparts. Specifically, cluster membership predicted functional but not clinical outcome. Our findings support the existence of distinct cognitive subgroups in CHR-P individuals that are associated with functional outcomes, with implications for early intervention and the understanding of underlying developmental processes.

Duration of basic and attenuated-psychotic symptoms in individuals at clinical high risk for psychosis: pattern of symptom onset and effects of duration on functioning and cognition.

INTRODUCTION: Duration of risk symptoms (DUR) in people at clinical high risk for psychosis (CHR-P) has been related to poorer clinical outcomes, such as reduced functioning, but it is currently unclear how different symptoms emerge as well as their link with cognitive deficits. To address these questions, we examined the duration of basic symptoms (BS) and attenuated psychotic symptoms (APS) in a sample of CHR-P participants to test the hypothesis that BS precede the manifestation of APS. As a secondary objective, we investigated the relationship between DUR, functioning and neuropsychological deficits. METHODS: Data from 134 CHR-P participants were assessed with the Comprehensive Assessment of At-Risk Mental State and the Schizophrenia Proneness Interview, Adult Version. Global, role and social functioning and neurocognition were assessed and compared to a sample of healthy controls (n = 57). RESULTS: In CHR-P participants who reported both APS and BS, onset of BS and APS was not significantly related. When divided into short and long BS duration ( 8 years), CHR-P participants with a longer duration of BS showed evidence for an onset of BS preceding APS (n = 8, p = 0.003). However, in the short BS duration group, APS showed evidence of preceding BS (n = 56, p = 0.020). Finally, there were no significant effects of DUR on cognition or functioning measures. CONCLUSION: The present findings do not support the view that APS constitute a secondary phenomenon to BS. Moreover, our data could also not confirm that DUR has a significant effect on functioning and cognitive deficits. These findings are discussed in the context of current theories regarding emerging psychosis and the importance of DUR.

Neuropsychological deficits in participants at clinical high risk for psychosis recruited from the community: relationships to functioning and clinical symptoms.

BACKGROUND: The current study examined the pattern of neurocognitive impairments in a community-recruited sample of clinical high-risk (CHR) participants and established relationships with psychosocial functioning. METHODS: CHR-participants (n = 108), participants who did not fulfil CHR-criteria (CHR-negatives) (n = 42) as well as a group of healthy controls (HCs) (n = 55) were recruited. CHR-status was assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult Version (SPI-A). The Brief Assessment of Cognition in Schizophrenia Battery (BACS) as well as tests for emotion recognition, working memory and attention were administered. In addition, role and social functioning as well as premorbid adjustment were assessed. RESULTS: CHR-participants were significantly impaired on the Symbol-Coding and Token-Motor task and showed a reduction in total BACS-scores. Moreover, CHR-participants were characterised by prolonged response times (RTs) in emotion recognition as well as by reductions in both social and role functioning, GAF and premorbid adjustments compared with HCs. Neurocognitive impairments in emotion recognition accuracy, emotion recognition RT, processing speed and motor speed were associated with several aspects of functioning explaining between 4% and 12% of the variance. CONCLUSION: The current data obtained from a community sample of CHR-participants highlight the importance of dysfunctions in motor and processing speed and emotion recognition RT. Moreover, these deficits were found to be related to global, social and role functioning, suggesting that neurocognitive impairments are an important aspect of sub-threshold psychotic experiences and a possible target for therapeutic interventions.

The Youth Mental Health Risk and Resilience Study (YouR-Study).

BACKGROUND: The transition from adolescence to adulthood is associated with the emergence of psychosis and other mental health problems, highlighting the importance of this developmental period for the understanding of developing psychopathology and individual differences in risk and resilience. The Youth Mental Health Risk and Resilience Study (YouR-Study) aims to identify neurobiological mechanisms and predictors of psychosis-risk with a state-of-the-art neuroimaging approach (Magnetoencephalography, Magnetic Resonance Spectroscopy, Magnetic Resonance Imaging) in combination with core psychological processes, such as affect regulation and attachment, that have been implicated in the development and maintenance of severe mental health problems. METHODS/DESIGN: One hundred participants meeting clinical high-risk criteria (CHR) for psychosis through the Comprehensive Assessment of At-Risk Mental State and Schizophrenia Proneness Instrument, Adult Version, in the age range from 16 to 35 years of age will be recruited. Mental-state monitoring up to a total of 2 years will be implemented to detect transition to psychosis. In addition, a sample of n = 40 help-seeking participants will be recruited who do not meet CHR-criteria, a group of n = 50 healthy control participants and a sample of n = 25 patients with first-episode psychosis. MEG-activity will be obtained during auditory and visual tasks to examine neural oscillations and event-related fields. In addition, we will obtain estimates of GABA and Glutamate levels through Magnetic Resonance Spectroscopy (MRS) to examine relationships between neural synchrony and excitatory-inhibition (E/I) balance parameters. Neuroimaging will be complemented by detailed neuropsychological assessments as well as psychological measures investigating the impact of childhood abuse, attachment experiences and affect regulation. DISCUSSION: The YouR-study could potentially provide important insights into the neurobiological mechanisms that confer risk for psychosis as well as biomarkers for early diagnosis of severe mental health problems. Moreover, we expect novel data related to the contribution of affect regulation and attachment-processes in the development of mental health problems, leading to an integrative model of early stage psychosis and the factors underlying risk and resilience of emerging psychopathology.

Components of therapy as mechanisms of change in cognitive therapy for people at risk of psychosis: analysis of the EDIE-2 trial.

BACKGROUND: Research suggests that the way in which cognitive therapy is delivered is an important factor in determining outcomes. We test the hypotheses in which the development of a shared problem list, use of case formulation, homework tasks and active intervention strategies will act as process variables. METHOD: Presence of these components during therapy is taken from therapist notes. The direct and indirect effect of the intervention is estimated by an instrumental variable analysis. RESULTS: A significant decrease in the symptom score for case formulation (coefficient = -23, 95% CI -44 to -1.7, P = 0.036) and homework (coefficient = -0.26, 95% CI -0.51 to -0.001, P = 0.049) is found. Improvement with the inclusion of active change strategies is of borderline significance (coefficient = -0.23, 95% CI -0.47 to 0.005, P = 0.056). CONCLUSIONS: There is a greater treatment effect if formulation and homework are involved in therapy. However, high correlation between components means that these may be indicators of overall treatment fidelity.

Fear of recurrence: results of a randomized trial of relapse detection in schizophrenia.

OBJECTIVE: We aimed to develop and establish the reliability and validity of a measure of Fear of Recurrence, measuring cognitive appraisals of relapse rather than standard early signs of relapse. We also aimed to establish the sensitivity and specificity to relapse. METHOD: Participants diagnosed with schizophrenia or a related disorder were randomized to one of two early signs monitoring conditions, using either the Early Signs Scale or the Fear of Recurrence Scale (FoRSe). Participants were followed up for 6-months or until relapse. RESULTS: A total of 169 participants were randomized to Standard (n = 86) or FoRSe (n = 83) monitoring. We found good evidence supporting reliability and validity of the FoRSe. In addition, a cut-off point of ≥ 5 was associated with an optimal sensitivity in both Standard (n = 26:79%, 95% CI = 62-89) and FoRSe (n = 18:72%, 95% CI = 52-86) monitoring. However, this degree of sensitivity was associated with a lower specificity in Standard (n = 30:35%, 96% CI = 23-50) and FoRSe (n = 25:46%, 95% CI = 32-60). Finally, Fear of Relapse was a significant predictor of time to relapse [Exp(ß) = 1.20, 95% CI = 1.01-1.42, p < .05]. CONCLUSION: The study provides evidence that Fear of Recurrence may be an important clinical construct linked to increased risk of relapse and poorer emotional recovery in people diagnosed with schizophrenia. PRACTITIONER POINTS: Monitoring Fear of Recurrence is as sensitive to relapse detection as monitoring early signs alone. Greater Fear of Relapse was associated with shorter duration to actual relapse. Fear of recurrence may be an important clinical feature linked to poorer emotional recovery and increased risk of relapse. Fear of Recurrence may be an important focus of psychological therapy to promote emotional recovery and prevention of relapse.

Intact Mismatch Negativity Responses in Clinical High Risk for Psychosis and First-Episode Psychosis: Evidence From Source-Reconstructed Event-Related Fields and Time-Frequency Data.

BACKGROUND: This study examined whether mismatch negativity (MMN) responses are impaired in participants at clinical high risk for psychosis (CHR-P) and patients with first-episode psychosis (FEP) and whether MMN deficits predict clinical outcomes in CHR-Ps. METHODS: Magnetoencephalography data were collected during a duration-deviant MMN paradigm for a group of 116 CHR-P participants, 33 FEP patients (15 antipsychotic-naïve), clinical high risk negative group (n = 38) with substance abuse and affective disorder, and 49 healthy control participants. Analysis of group differences of source-reconstructed event-related fields as well as time-frequency and intertrial phase coherence focused on the bilateral Heschl's gyri and bilateral superior temporal gyri. RESULTS: Significant magnetic MMN responses were found across participants in the bilateral Heschl's gyri and bilateral superior temporal gyri. However, MMN amplitude as well as time-frequency and intertrial phase coherence responses were intact in CHR-P participants and FEP patients compared with healthy control participants. Furthermore, MMN deficits were not related to persistent attenuated psychotic symptoms or transitions to psychosis in CHR-P participants. CONCLUSIONS: Our data suggest that magnetic MMN responses in magnetoencephalography data are not impaired in early-stage psychosis and may not predict clinical outcomes in CHR-P participants.

Impact of cognitive therapy on internalised stigma in people with at-risk mental states.

BACKGROUND: Internalised stigma in young people meeting criteria for at-risk mental states (ARMS) has been highlighted as an important issue, and it has been suggested that provision of cognitive therapy may increase such stigma. AIMS: To investigate the effects of cognitive therapy on internalised stigma using a secondary analysis of data from the EDIE-2 trial. METHOD: Participants meeting criteria for ARMS were recruited as part of a multisite randomised controlled trial of cognitive therapy for prevention and amelioration of psychosis. Participants were assessed at baseline and at 6, 12, 18 and 24 months using measures of psychotic experiences, symptoms and internalised stigma. RESULTS: Negative appraisals of experiences were significantly reduced in the group assigned to cognitive therapy (estimated difference at 12 months was -1.36 (95% CI -2.69 to -0.02), P = 0.047). There was no difference in social acceptability of experiences (estimated difference at 12 months was 0.46, 95% CI -0.05 to 0.98, P = 0.079). CONCLUSIONS: These findings suggest that, rather than increasing internalised stigma, cognitive therapy decreases negative appraisals of unusual experiences in young people at risk of psychosis; as such, it is a non-stigmatising intervention for this population.

Depression and anxiety following psychosis: associations with mindfulness and psychological flexibility.

BACKGROUND: Individuals experiencing psychosis can present with elevated levels of depression and anxiety. Research suggests that aspects of depression and anxiety may serve an avoidant function by limiting the processing of more distressing material. Acceptance and Commitment Therapy suggests that avoidance of aversive mental experiences contributes to psychological inflexibility. Depression and anxiety occurring in the context of psychosis have a limiting effect on quality of life. No research to date has investigated how levels of psychological flexibility and mindfulness are associated with depression and anxiety occurring following psychosis. AIMS: This study investigated associations psychological flexibility and mindfulness had with depression and anxiety following psychosis. METHOD: Thirty participants with psychosis were recruited by consecutive referral on the basis that they were experiencing emotional dysfunction following psychosis. The Hospital Anxiety and Depression Scale (HADS), Positive and Negative Syndrome Scale (PANSS), Acceptance and Action Questionnaire (AAQ-II) and the Kentucky Inventory of Mindfulness Skills (KIMS) were used. A cross-sectional correlational design was used. RESULTS: The depression and anxiety subscales of the HADS both had significant correlations with psychological flexibility (as assessed by the AAQ-II) and aspects of mindfulness (as assessed by the KIMS). Hierarchical regression analyses indicated that psychological flexibility, but not mindfulness, contributed significantly to models predicting 46% of variance in both depression and anxiety scores. CONCLUSIONS: Although aspects of mindfulness are associated with depression and anxiety following an episode of psychosis, psychological flexibility appears to account for a larger proportion of variance in depression and anxiety scores in this population.

Investigating temporal and prosodic markers in clinical high-risk for psychosis participants using automated acoustic analysis.

AIM: Language disturbances are a candidate biomarker for the early detection of psychosis. Temporal and prosodic abnormalities have been observed in schizophrenia patients, while there is conflicting evidence whether such deficits are present in participants meeting clinical high-risk for psychosis (CHR-P) criteria. METHODS: Clinical interviews from CHR-P participants (n = 50) were examined for temporal and prosodic metrics and compared against a group of healthy controls (n = 17) and participants with affective disorders and substance abuse (n = 23). RESULTS: There were no deficits in acoustic variables in the CHR-P group, while participants with affective disorders/substance abuse were characterized by slower speech rate, longer pauses and higher unvoiced frames percentage. CONCLUSION: Our finding suggests that temporal and prosodic aspects of speech are not impaired in early-stage psychosis. Further studies are required to clarify whether such abnormalities are present in sub-groups of CHR-P participants with elevated psychosis-risk.

Thalamo-cortical circuits during sensory attenuation in emerging psychosis: a combined magnetoencephalography and dynamic causal modelling study.

Evidence suggests that schizophrenia (ScZ) involves impairments in sensory attenuation. It is currently unclear, however, whether such deficits are present during early-stage psychosis as well as the underlying network and the potential as a biomarker. To address these questions, Magnetoencephalography (MEG) was used in combination with computational modeling to examine M100 responses that involved a "passive" condition during which tones were binaurally presented, while in an "active" condition participants were asked to generate a tone via a button press. MEG data were obtained from 109 clinical high-risk for psychosis (CHR-P) participants, 23 people with a first-episode psychosis (FEP), and 48 healthy controls (HC). M100 responses at sensor and source level in the left and right thalamus (THA), Heschl's gyrus (HES), superior temporal gyrus (STG) and right inferior parietal cortex (IPL) were examined and dynamic causal modeling (DCM) was performed. Furthermore, the relationship between sensory attenuation and persistence of attenuated psychotic symptoms (APS) and transition to psychosis was investigated in CHR-P participants. Sensory attenuation was impaired in left HES, left STG and left THA in FEP patients, while in the CHR-P group deficits were observed only in right HES. DCM results revealed that CHR-P participants showed reduced top-down modulation from the right IPL to the right HES. Importantly, deficits in sensory attenuation did not predict clinical outcomes in the CHR-P group. Our results show that early-stage psychosis involves impaired sensory attenuation in auditory and thalamic regions but may not predict clinical outcomes in CHR-P participants.

Hippocampal structural alterations in early-stage psychosis: Specificity and relationship to clinical outcomes.

Hippocampal dysfunctions are a core feature of schizophrenia, but conflicting evidence exists whether volumetric and morphological changes are present in early-stage psychosis and to what extent these deficits are related to clinical trajectories. In this study, we recruited individuals at clinical high risk for psychosis (CHR-P) (n = 108), patients with a first episode of psychosis (FEP) (n = 37), healthy controls (HC) (n = 70) as well as a psychiatric control group with substance abuse and affective disorders (CHR-N: n = 38). MRI-data at baseline were obtained and volumetric as well as vertex analyses of the hippocampus were carried out. Moreover, volumetric changes were examined in the amygdala, caudate, nucleus accumbens, pallidum, putamen and thalamus. In addition, we obtained follow-up functional and symptomatic assessments in CHR-P individuals to examine the question whether anatomical deficits at baseline predicted clinical trajectories. Our results show that the hippocampus is the only structure showing significant volumetric decrease in early-stage psychosis, with FEPs showing significantly smaller hippocampal volumes bilaterally alongside widespread shape changes in the vertex analysis. For the CHR-P group, volumetric decreases were confined to the left hippocampus. However, hippocampal alterations in the CHR-P group were not robustly associated with clinical outcomes, including the persistence of attenuated psychotic symptoms and functional trajectories. Accordingly, our findings highlight that dysfunctions in hippocampal anatomy are an important feature of early-stage psychosis which may, however, not be related to clinical outcomes in CHR-P participants.

MR-Spectroscopy of GABA and Glutamate/Glutamine Concentrations in Auditory Cortex in Clinical High-Risk for Psychosis Individuals.

Psychosis involves changes in GABAergic and glutamatergic neurotransmission in auditory cortex that could be important for understanding sensory deficits and symptoms of psychosis. However, it is currently unclear whether such deficits are present in participants at clinical high-risk for psychosis (CHR-P) and whether they are associated with clinical outcomes. Magnetic Resonance Spectroscopy (MEGAPRESS, 1H-MRS at 3 Tesla) was used to estimate GABA, glutamate, and glutamate-plus-glutamine (Glx) levels in auditory cortex in a large sample of CHR-P (n = 99), CHR-N (clinical high-risk negative, n = 32), and 45 healthy controls. Examined were group differences in metabolite concentrations as well as relationships with clinical symptoms, general cognition, and 1-year follow-up clinical and general functioning in the CHR-P group. Results showed a marginal (p = 0.039) main group effect only for Glx, but not for GABA and glutamate concentrations, and only in left, not right, auditory cortex. This effect did not survive multiple comparison correction, however. Exploratory post-hoc tests revealed that there were significantly lower Glx levels (p = 0.029, uncorrected) in the CHR-P compared to the CHR-N group, but not relative to healthy controls (p = 0.058, uncorrected). Glx levels correlated with the severity of perceptual abnormalities and disorganized speech scores. However, in the CHR-P group, Glx levels did not predict clinical or functional outcomes. Accordingly, the findings from the present study suggest that MRS-measured GABA, glutamate and Glx levels in auditory cortex of CHR-P individuals are largely intact.

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

BACKGROUND: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. OBJECTIVE: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? DESIGN: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. SETTINGS: Glasgow, UK, and Melbourne, Australia. PARTICIPANTS: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. INTERVENTIONS: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. MAIN OUTCOME MEASURES: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. RESULTS: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. LIMITATIONS: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. CONCLUSIONS: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. FUTURE WORK: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). TRIAL REGISTRATION: This trial is registered as ISRCTN99559262. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

WHAT WAS THE PROBLEM?: Relapse is a considerable problem for people with a diagnosis of schizophrenia. Relapse can be predicted by early warning signs that are unique to the person. They include withdrawal, fear and paranoia. WHAT WAS THE QUESTION?: Is it possible to investigate the effectiveness of an intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? WHAT DID WE DO?: We spoke with 88 mental health staff, 40 carers and 21 service users before we designed a system that used a mobile phone to help people monitor early warning signs. We included peer support to help people using the system reflect on their experiences. We hoped the overall system, called EMPOWER, would help people to be more in charge of their mental health. After consenting 86 people to the study, we were able to randomly assign 73 people either to use the EMPOWER system (42 people) or to receive their normal treatment alone (31 people). We used research measures over 1 year to help us better understand people's experiences. We also involved carers (for example family or friends) and mental health service providers in the research. WHAT DID WE FIND?: We found that it was possible to recruit people to the study and to gather research data. We also found that people used the EMPOWER system and found it acceptable. We found that those who used EMPOWER had a lower rate of relapse over 12 months than people who did not. They were also less likely to be fearful of relapse. We found that EMPOWER was likely to be cost-effective. WHAT DOES THIS MEAN?: This means that a study to investigate the effectiveness of a system to recognise and respond to early warning signs of relapse in schizophrenia is possible.

The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia.

BACKGROUND: Early warning signs monitoring by service users with schizophrenia has shown promise in preventing relapse but the quality of evidence is low. We aimed to establish the feasibility of undertaking a definitive randomised controlled trial to determine the effectiveness of a blended digital intervention for relapse prevention in schizophrenia. METHODS: This multicentre, feasibility, cluster randomised controlled trial aimed to compare Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) with treatment as usual in community mental health services (CMHS) in Glasgow and Melbourne. CMHS were the unit of randomisation, selected on the basis of those that probably had five or more care coordinators willing to participate. Participants were eligible if they were older than 16 years, had a schizophrenia or related diagnosis confirmed via case records, were able to provide informed consent, had contact with CMHS, and had had a relapse within the previous 2 years. Participants were randomised within stratified clusters to EMPOWER or to continue their usual approach to care. EMPOWER blended a smartphone for active monitoring of early warning signs with peer support to promote self-management and clinical triage to promote access to relapse prevention. Main outcomes were feasibility, acceptability, usability, and safety, which was assessed through face-to-face interviews. App usage was assessed via the smartphone and self-report. Primary end point was 12 months. Participants, research assistants and other team members involved in delivering the intervention were not masked to treatment conditions. Assessment of relapse was done by an independent adjudication panel masked to randomisation group. The study is registered at ISRCTN (99559262). FINDINGS: We identified and randomised eight CMHS (six in Glasgow and two in Melbourne) comprising 47 care coordinators. We recruited 86 service users between Jan 19 and Aug 8, 2018; 73 were randomised (42 [58%] to EMPOWER and 31 [42%] to treatment as usual). There were 37 (51%) men and 36 (49%) women. At 12 months, main outcomes were collected for 32 (76%) of service users in the EMPOWER group and 30 (97%) of service users in the treatment as usual group. Of those randomised to EMPOWER, 30 (71%) met our a priori criterion of more than 33% adherence to daily monitoring that assumed feasibility. Median time to discontinuation of these participants was 31·5 weeks (SD 14·5). There were 29 adverse events in the EMPOWER group and 25 adverse events in the treatment as usual group. There were 13 app-related adverse events, affecting 11 people, one of which was serious. Fear of relapse was lower in the EMPOWER group than in the treatment as usual group at 12 months (mean difference -7·53 (95% CI -14·45 to 0·60; Cohen's d -0·53). INTERPRETATION: A trial of digital technology to monitor early warning signs blended with peer support and clinical triage to detect and prevent relapse appears to be feasible, safe, and acceptable. A further main trial is merited. FUNDING: UK National Institute for Health Research Health Technology Assessment programme and the Australian National Health and Medical Research Council.

Metacognition and persecutory delusions: tests of a metacognitive model in a clinical population and comparisons with non-patients.

BACKGROUND. A metacognitive approach to the conceptualization of paranoia as a strategy for managing interpersonal threat has gained some support in studies of non-clinical populations. This study reports a clinical validation of the Beliefs about Paranoia Scale (BaPS), a self-report measure to assess metacognitive beliefs about paranoia. We aimed to replicate the factor structure of a brief version of the measure and test the specific hypotheses that positive beliefs about paranoia would predict levels of suspiciousness, and that negative beliefs about paranoia would predict problematic persecutory delusions. METHOD. A total of 122 patients meeting criteria for a diagnosis of a schizophrenia spectrum disorder completed the questionnaire assessing beliefs about paranoia. In addition, 61 of the participants were administered the Structured Clinical Interview for DSM-IV, and 60 were administered the Positive and Negative Syndromes of Schizophrenia Scale. One hundred and seventy-eight non-patients were also recruited (an undergraduate sample). RESULTS. Principal components factor analysis showed that the three-factor solution was replicated (comprising negative beliefs about paranoia, paranoia as a survival strategy, and normalizing beliefs). This measure showed good internal consistency (alphas ranged from .85 to .91). Correlational analyses revealed that positive beliefs about paranoia were positively associated with levels of suspiciousness, and independent t tests showed that negative beliefs about paranoia were significantly higher in patients with a diagnosis of schizophrenia meeting criteria for persecutory delusions in comparison to those without. Analyses of covariance showed that patients scored higher than non-patients on both positive and negative beliefs, but logistic regression did not demonstrate that co-occurrence of these beliefs predicted patient status. CONCLUSIONS. Three of our four hypotheses were confirmed, suggesting that a metacognitive approach to the conceptualization of paranoia as a strategy for managing interpersonal threat may have some utility for understanding clinical paranoia. Such a model is described and the clinical implications of the findings are also discussed.

The development and validation of the Beliefs about Paranoia Scale (Short Form).

BACKGROUND: This study reports the development and revision of the Beliefs about Paranoia Scale (BaPS), a self-report measure to assess metacognitive beliefs about paranoia in non-patients. We aimed to confirm the factor structure of a revised 50-item version of the measure and test the specific hypotheses that positive beliefs about paranoia would predict frequency of paranoia, and that negative beliefs about paranoia would predict distress associated with paranoia. METHOD: 185 non-patient participants completed questionnaires assessing beliefs about paranoia, thought control, self-consciousness, anxiety, depression and paranoia. RESULTS: The results showed that the original four-factor solution could not be replicated. Instead a three-factor solution comprising Negative Beliefs about Paranoia, Paranoia as a Survival Strategy, and Normalizing Beliefs was developed. The revised 18-item measure showed good internal consistency. Stepwise regression analysis showed that, BaPS-negative beliefs accounted for 34% of the variance with R2 of 0.339, with a multiple R of 0.585 in relation to frequency of paranoia. In relation to distress arising from paranoia, stepwise regression analysis showed that BaPS-negative beliefs accounted for 34% of the variance with R2 of 0.339, with a multiple R of 0.585. In both analyses, BaPS-Survival strategy showed a small but significant incremental increase in the variance accounted for in the overall model. CONCLUSIONS: These findings suggest that a metacognitive approach to the conceptualization of paranoia as a strategy for managing interpersonal threat may have some utility. The clinical implications of the findings are also discussed.

Prevalence and predictors of suicidality and non-suicidal self-harm among individuals at clinical high-risk for psychosis: Results from a community-recruited sample.

AIM: Suicidal thoughts and behaviours are prevalent in individuals with schizophrenia. However, research examining the prevalence and predictors of suicidality and self-harm in participants at clinical high-risk for psychosis (CHR-P) is limited and mostly focuses on help-seeking participants recruited through clinical pathways. The current study sought to assess the prevalence of suicidality and self-harm and identify predictors of current suicidal ideation in community-recruited CHR-P participants. METHODS: Data were available for 130 CHR-P participants, 15 participants with first-episode psychosis (FEP), 47 participants not fulfilling CHR-P criteria (CHR-Ns) and 53 healthy controls. Current and lifetime suicidality and self-harm were assessed using the Mini-International Neuropsychiatric Interview and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Multivariable logistic regression analysis was used to determine predictors of current suicidal ideation in the CHR-P group. RESULTS: A considerable proportion of CHR-P participants disclosed current suicidal ideation (34.6%). Overall, FEP individuals were at greatest risk, with considerably high prevalence rates for current suicidal ideation (73.3%), lifetime self-harm behaviour (60.0%) and lifetime suicide attempt (60.0%). In the CHR-P sample, current suicidal ideation was predicted by lifetime suicide attempts, lower CAARMS severity, impaired social functioning and greater comorbidity. CONCLUSIONS: Our findings suggest that suicidality and self-harm are highly prevalent in community-recruited CHR-P and FEP individuals. Accordingly, these results highlight the importance of further research into the determinants of suicidality and self-harm during at-risk and early stages of psychosis, and the implementation of intervention strategies to reduce adverse outcomes in these populations.

The relationship between cognitive deficits and impaired short-term functional outcome in clinical high-risk for psychosis participants: A machine learning and modelling approach.

Poor functional outcomes are common in individuals at clinical high-risk for psychosis (CHR-P), but the contribution of cognitive deficits remains unclear. We examined the potential utility of cognitive variables in predictive models of functioning at baseline and follow-up with machine learning methods. Additional models fitted on baseline functioning variables were used as a benchmark to evaluate model performance. Data were available for 1) 146 CHR-P individuals of whom 118 completed a 6- and/or 12-month follow-up, 2) 47 participants not fulfilling CHR criteria (CHR-Ns) but displaying affective and substance use disorders and 3) 55 healthy controls (HCs). Predictors of baseline global assessment of functioning (GAF) scores were selected by L1-regularised least angle regression and then used to train classifiers to predict functional outcome in CHR-P individuals. In CHR-P participants, cognitive deficits together with clinical and functioning variables explained 41% of the variance in baseline GAF scores while cognitive variables alone explained 12%. These variables allowed classification of functional outcome with an average balanced accuracy (BAC) of 63% in both mixed- and cross-site models. However, higher accuracies (68%-70%) were achieved using classifiers fitted only on baseline functioning variables. Our findings suggest that cognitive deficits, alongside clinical and functioning variables, displayed robust relationships with impaired functioning in CHR-P participants at baseline and follow-up. Moreover, these variables allow for prediction of functional outcome. However, models based on baseline functioning variables showed a similar performance, highlighting the need to develop more accurate algorithms for predicting functional outcome in CHR-P participants.