Dietary intake, physical activity and sedentary behaviour patterns in a sample with established psychosis and associations with mental health symptomatology.

BACKGROUND: People with psychosis experience cardiometabolic comorbidities, including metabolic syndrome, coronary heart disease and diabetes. These physical comorbidities have been linked to diet, inactivity and the effects of the illness itself, including disorganisation, impairments in global function and amotivation associated with negative symptoms of schizophrenia or co-morbid depression. METHODS: We aimed to describe the dietary intake, physical activity (PA) and sedentary behaviour patterns of a sample of patients with established psychosis participating in the Improving Physical Health and Reducing Substance Use in Severe Mental Illness (IMPaCT) randomised controlled trial, and to explore the relationship between these lifestyle factors and mental health symptomatology. RESULTS: A majority of participants had poor dietary quality, low in fruit and vegetables and high in discretionary foods. Only 29.3% completed ⩾150 min of moderate and/or vigorous activity per week and 72.2% spent ⩾6 h per day sitting. Cross-sectional associations between negative symptoms, global function, and PA and sedentary behaviour were observed. Additionally, those with more negative symptoms receiving IMPaCT therapy had fewer positive changes in PA from baseline to 12-month follow-up than those with fewer negative symptoms at baseline. CONCLUSION: These results highlight the need for the development of multidisciplinary lifestyle and exercise interventions to target eating habits, PA and sedentary behaviour, and the need for further research on how to adapt lifestyle interventions to baseline mental status. Negative symptoms in particular may reduce patient's responses to lifestyle interventions.

Applying the cultural adaption framework to the Early Youth Engagement (EYE-2) approach to early intervention in psychosis.

OBJECTIVES: Disengagement from Early Intervention in Psychosis (EIP) services is pronounced in individuals from racially minoritized or diverse ethnic backgrounds, lesbian, gay, bisexual, transgender, and queer or questioning individuals, and individuals from some religious or spiritual backgrounds. The Early Youth Engagement in first episode psychosis study (EYE-2) is a cluster randomized controlled trial that tests a new engagement intervention. The current study aimed to (i) explore perspectives of service users from diverse backgrounds in relation to spirituality, ethnicity, culture and sexuality on engagement and the EYE-2 approach and (ii) use an evidence-based adaptation framework to incorporate their needs and perspectives into the EYE-2 resources and training. METHODS: This qualitative study used semi-structured interviews to explore service users' experiences and perspectives on EYE-2 approaches and resources. The study was conducted within EIP teams across three inner-city sites in England chosen to reflect diverse urban populations. Topic guides covered participant's identity, perceptions of EYE-2 resources, and experience of using mental health services. Transcribed interviews underwent thematic analysis. RESULTS: In this study, 21 service users aged 18 to 35 (M = 25.4; SD = 5.5) participated in semi-structured interviews. Seven key themes were identified across the four domains of the cultural adaptation framework: Differing cognitions and beliefs; multiple facets of culture; language as a barrier to engagement; stigma and discrimination; adaptations to EYE-2 resources; trust in therapeutic alliance; and individual differences in therapeutic preferences. CONCLUSIONS: The emergent themes highlighted a need to cater to various aspects of cultural diversity when developing EIP materials and services.

A systematic review and meta-analysis of digital interventions targeted at individuals with borderline personality disorder (BPD), emotionally unstable personality disorder (EUPD), and related symptoms.

OBJECTIVES: The present review investigates the impact of digital interventions for individuals with features of borderline personality disorder (BPD)/emotional unstable personality disorder (EUPD) as digital interventions show promise as therapeutic tools in underserved groups. BPD/EUPD features are identified as clinically relevant, yet previous reviews on the use of digital interventions fail to include subthreshold symptomatology. METHODS: Five online databases were searched for terminology in three categories: BPD/EUPD and related symptoms, mental-health interventions, and digital technology. Additionally, four relevant journals and two trial registers were searched for additional papers meeting the inclusion criteria. RESULTS: Twelve articles met all inclusion criteria. Meta-analyses revealed statistically significant differences in symptom measures between intervention and control groups at postintervention and decreases in BPD/EUPD symptomatology and well-being from pre- to postintervention. Service users' engagement, satisfaction, and acceptability of interventions were high. Results support the previous literature on the value of using digital interventions in populations with BPD/EUPD. CONCLUSION: Overall, it was identified that digital interventions show promise for successful implementation with this population.

A qualitative process evaluation of social recovery therapy for enhancement of social recovery in first-episode psychosis (SUPEREDEN3).

BACKGROUND: Many individuals with first-episode psychosis experience severe and persistent social disability despite receiving specialist early intervention. The SUPEREDEN3 trial assessed whether augmenting early intervention in psychosis services with Social Recovery Therapy (SRT) would lead to better social recovery. AIMS: A qualitative process evaluation was conducted to explore implementation and mechanisms of SRT impact from the perspective of SUPEREDEN3 participants. METHOD: A subsample of SUPEREDEN3 trial participants (n = 19) took part in semi-structured interviews, which were transcribed verbatim and analysed thematically. Trial participants were early intervention service users aged 16-35 years with severe and persistent social disability. Both SRT plus early intervention and early intervention alone arm participants were interviewed to facilitate better understanding of the context in which SRT was delivered and to aid identification of mechanisms specific to SRT. RESULTS: The six themes identified were used to generate an explanatory model of SRT's enhancement of social recovery. Participant experiences highlight the importance of the therapist cultivating increased self-understanding and assertively encouraging clients to face feared situations in a way that is perceived as supportive, while managing ongoing symptoms. The sense of achievement generated by reaching targets linked to personally meaningful goals promotes increased self-agency, and generates hope and optimism. CONCLUSIONS: The findings suggest potentially important processes through which social recovery was enhanced in this trial, which will be valuable in ensuring the benefits observed can be replicated. Participant accounts provide hope that, with the right support, even clients who have persistent symptoms and the most severe disability can make a good social recovery.

Clinical insight in first episode psychosis: the role of metacognition.

BACKGROUND: Poor clinical insight has been commonly reported in those with First Episode Psychosis (FEP) and thought to be influenced by a range of factors, including neurocognition and symptoms. Clinical insight may be compromised as a result of alterations in higher-level reflective processes, such as metacognitive ability and cognitive insight. AIMS: To explore whether metacognitive ability and cognitive insight are associated with clinical insight while controlling for IQ, depression, and symptoms in FEP. METHODS: 60 individuals with FEP completed measures for clinical insight, metacognitive ability, cognitive insight, positive and negative symptoms, depression, and IQ. RESULTS: Higher levels of metacognitive ability were associated with better clinical insight, even when controlling for IQ, depression, positive and negative symptoms, and medication. Integration subscale of metacognitive ability was most strongly associated with clinical insight. Cognitive insight was associated with clinical insight when controlling for covariates. However, when including metacognitive ability and cognitive insight in the predictive model, only metacognitive ability was significantly related to clinical insight. DISCUSSION: Metacognitive ability, specifically the ability to describe one's evolving mental state to provide a coherent narrative, was significantly related to clinical insight, independent of covariates, and may be a potentially important target for intervention in FEP.

Clinical and cost-effectiveness of social recovery therapy for the prevention and treatment of long-term social disability among young people with emerging severe mental illness (PRODIGY): randomised controlled trial.

BACKGROUND: Young people with social disability and severe and complex mental health problems have poor outcomes, frequently struggling with treatment access and engagement. Outcomes may be improved by enhancing care and providing targeted psychological or psychosocial intervention. AIMS: We aimed to test the hypothesis that adding social recovery therapy (SRT) to enhanced standard care (ESC) would improve social recovery compared with ESC alone. METHOD: A pragmatic, assessor-masked, randomised controlled trial (PRODIGY: ISRCTN47998710) was conducted in three UK centres. Participants (n = 270) were aged 16-25 years, with persistent social disability, defined as under 30 hours of structured activity per week, social impairment for at least 6 months and severe and complex mental health problems. Participants were randomised to ESC alone or SRT plus ESC. SRT was an individual psychosocial therapy delivered over 9 months. The primary outcome was time spent in structured activity 15 months post-randomisation. RESULTS: We randomised 132 participants to SRT plus ESC and 138 to ESC alone. Mean weekly hours in structured activity at 15 months increased by 11.1 h for SRT plus ESC (mean 22.4, s.d. = 21.4) and 16.6 h for ESC alone (mean 27.7, s.d. = 26.5). There was no significant difference between arms; treatment effect was -4.44 (95% CI -10.19 to 1.31, P = 0.13). Missingness was consistently greater in the ESC alone arm. CONCLUSIONS: We found no evidence for the superiority of SRT as an adjunct to ESC. Participants in both arms made large, clinically significant improvements on all outcomes. When providing comprehensive evidence-based standard care, there are no additional gains by providing specialised SRT. Optimising standard care to ensure targeted delivery of existing interventions may further improve outcomes.

Associations between responses to voices, distress and appraisals during daily life: an ecological validation of the cognitive behavioural model.

BACKGROUND: Cognitive models propose that behavioural responses to voices maintain distress by preventing disconfirmation of negative beliefs about voices. We used Experience Sampling Methodology (ESM) to examine the hypothesized maintenance role of behavioural responses during daily life. METHOD: Thirty-one outpatients with frequent voices completed a smartphone-based ESM questionnaire 10 times a day over 9 days, assessing voice-related distress; resistance and compliance responses to voices; voice characteristics (intensity and negative content); appraisals of voice dominance, uncontrollability and intrusiveness. RESULTS: In line with predictions, behavioural responses were associated with voice appraisals (dominance and uncontrollability), but not voice characteristics. Greater resistance and compliance were reported in moments of increased voice distress, but these associations did not persist after controlling for concurrent voice appraisals and characteristics. Voice distress was predicted by appraisals, and, unexpectedly, also by voice characteristics. As predicted, compliance and resistance were related to increases in distress at subsequent timepoints, whilst antecedent voice appraisals and characteristics had no such effect. Compliance, but not resistance, additionally predicted subsequent increases in voice uncontrollability. In both cases, the reverse models showed no association, indicating directional effects of responses on subsequent distress, and of compliance on uncontrollability appraisals. CONCLUSIONS: These results provide support for the cognitive model by suggesting that momentary behavioural and emotional responses to voices are associated with concurrent negative voice appraisals. Findings suggest that behavioural responses may be driven by voice appraisals, rather than directly by distress, and may in turn maintain voice appraisals and associated distress during the course of daily life.

The impact of Patient and Public Involvement in the SlowMo study: Reflections on peer innovation.

BACKGROUND: The SlowMo study demonstrated the effects of SlowMo, an eight-session digitally supported reasoning intervention, on paranoia in a large-scale randomized-controlled trial with 362 participants with schizophrenia-spectrum psychosis. AIM: The current evaluation aimed to investigate the impact of Patient and Public Involvement (PPI) in the SlowMo study. METHOD: PPI members were six women and three men from Sussex, Oxford and London with experience of using mental health services for psychosis. They received training and met at least 3-monthly throughout the project. The impact of PPI was captured quantitatively and qualitatively through (i) a PPI log of recommendations and implementation; (ii) written subjective experiences of PPI members; (iii) meeting minutes; and (iv) outputs produced. RESULTS: The PPI log revealed 107 recommendations arising from PPI meetings, of which 87 (81%) were implemented. Implementation was greater for recruitment-, data collection- and organization-related actions than for dissemination and emergent innovations. Qualitative feedback revealed impacts on study recruitment, data collection, PPI participants' confidence, knowledge, career aspirations and society more widely. Outputs produced included a film about psychosis that aired on BBC primetime television, novel webpages and journal articles. Barriers to PPI impact included geography, travel, funding, co-ordination and well-being. DISCUSSION: A future challenge for PPI impact will be the extent to which peer innovation (innovative PPI-led ideas) can be supported within research study delivery. PATIENT AND PUBLIC CONTRIBUTION: Planned Patient and Public Contribution in SlowMo comprised consultation and collaboration in (i) design, (ii) recruitment, (iii) qualitative interviews and analysis of service users' experiences of SlowMo therapy and (iv) dissemination.

Perceptual biases and metacognition and their association with anomalous self experiences in first episode psychosis.

Anomalous self-experiences have been described as a prerequisite for anomalous perceptual experiences. Later, these anomalous perceptual experiences may then be metacognitively appraised as distressing, maintaining these experiences and later leading to anomalous (delusional) beliefs. This model of anomalous events may potentially be driven by perceptual biases and metacognitive deficits. This cross-sectional study explored the association between perceptual biases, metacognition and anomalous self- and perceptual experiences and delusional beliefs in First Episode Psychosis (FEP) and a matched healthy control sample. Fifty-eight individuals with FEP and seventy-two healthy controls were included in the main analysis. Increased auditory perceptual biases were significantly associated with increased state and trait anomalous self-experiences, in particular alienation from surroundings and emotional numbing. No significant associations were found between metacognitive efficiency and anomalous experiences. These findings may be consistent with the minimal self-disturbance model of schizophrenia spectrum vulnerability, particularly with the hyperreflexivity concept.

A meta-analytic review of the relationship between neurocognition, metacognition and functional outcome in schizophrenia.

Previous research has identified that neurocognition predicts functional outcome in schizophrenia to a greater extent than psychopathology. More contemporary authors have begun to explore the role of metacognition as a mediating variable between neurocognition and functional outcome. The present review sought to extend the known work by synthesising the results reported in individual studies to see if these results are consistently found across samples. Relevant search strategies were entered into Medline (PubMed), PsychINFO and Embase. The present meta-analysis encompassed 17 studies (N = 1060) investigating the relationship between neurocognition and metacognition and seven studies investigating the relationship between metacognition and functional outcome (N = 645). A small-to-moderate mean effect size was found between neurocognition and metacognition (effect size range: 0.13-0.58) and a small-to-moderate effect size was found between metacognition and functional outcome (range: 0.17-0.57). Study findings suggest that relationships between variables are consistently found across samples and that future research should focus on investigating this relationship at earlier stages of illness, in female cohorts and across cognitive domains. Greater investigation is required in functional outcome, differentiating the impact of metacognition on functional capacity and other domains of functional outcome.

Effect of lifestyle, medication and ethnicity on cardiometabolic risk in the year following the first episode of psychosis: prospective cohort study.

BACKGROUND: The first episode of psychosis is a critical period in the emergence of cardiometabolic risk. AIMS: We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis. METHOD: This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months. RESULTS: Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol). CONCLUSIONS: Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis (STEPWISE): randomised controlled trial.

BACKGROUND: Obesity is a major challenge for people with schizophrenia.AimsWe assessed whether STEPWISE, a theory-based, group structured lifestyle education programme could support weight reduction in people with schizophrenia. METHOD: In this randomised controlled trial (study registration: ISRCTN19447796), we recruited adults with schizophrenia, schizoaffective disorder or first-episode psychosis from ten mental health organisations in England. Participants were randomly allocated to the STEPWISE intervention or treatment as usual. The 12-month intervention comprised four 2.5 h weekly group sessions, followed by 2-weekly maintenance contact and group sessions at 4, 7 and 10 months. The primary outcome was weight change after 12 months. Key secondary outcomes included diet, physical activity, biomedical measures and patient-related outcome measures. Cost-effectiveness was assessed and a mixed-methods process evaluation was included. RESULTS: Between 10 March 2015 and 31 March 2016, we recruited 414 people (intervention 208, usual care 206) with 341 (84.4%) participants completing the trial. At 12 months, weight reduction did not differ between groups (mean difference 0.0 kg, 95% CI -1.6 to 1.7, P = 0.963); physical activity, dietary intake and biochemical measures were unchanged. STEPWISE was well-received by participants and facilitators. The healthcare perspective incremental cost-effectiveness ratio was £246 921 per quality-adjusted life-year gained. CONCLUSIONS: Participants were successfully recruited and retained, indicating a strong interest in weight interventions; however, the STEPWISE intervention was neither clinically nor cost-effective. Further research is needed to determine how to manage overweight and obesity in people with schizophrenia.Declaration of interestR.I.G.H. received fees for lecturing, consultancy work and attendance at conferences from the following: Boehringer Ingelheim, Eli Lilly, Janssen, Lundbeck, Novo Nordisk, Novartis, Otsuka, Sanofi, Sunovion, Takeda, MSD. M.J.D. reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceuticals International Inc.; and, grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Janssen. K.K. has received fees for consultancy and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Servier and Merck Sharp & Dohme. He has received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Pfizer, Boehringer Ingelheim and Merck Sharp & Dohme. K.K. has received funds for research, honoraria for speaking at meetings and has served on advisory boards for Lilly, Sanofi-Aventis, Merck Sharp & Dohme and Novo Nordisk. D.Sh. is expert advisor to the NICE Centre for guidelines; board member of the National Collaborating Centre for Mental Health (NCCMH); clinical advisor (paid consultancy basis) to National Clinical Audit of Psychosis (NCAP); views are personal and not those of NICE, NCCMH or NCAP. J.P. received personal fees for involvement in the study from a National Institute for Health Research (NIHR) grant. M.E.C. and Y.D. report grants from NIHR Health Technology Assessment, during the conduct of the study; and The Leicester Diabetes Centre, an organisation (employer) jointly hosted by an NHS Hospital Trust and the University of Leicester and who is holder (through the University of Leicester) of the copyright of the STEPWISE programme and of the DESMOND suite of programmes, training and intervention fidelity framework that were used in this study. S.R. has received honorarium from Lundbeck for lecturing. F.G. reports personal fees from Otsuka and Lundbeck, personal fees and non-financial support from Sunovion, outside the submitted work; and has a family member with professional links to Lilly and GSK, including shares. F.G. is in part funded by the National Institute for Health Research Collaboration for Leadership in Applied Health Research & Care Funding scheme, by the Maudsley Charity and by the Stanley Medical Research Institute and is supported by the by the Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London.

Beliefs in social inclusion: Invariance in associations among hope, dysfunctional attitudes, and social inclusion across adolescence and young adulthood.

Social disability in youth is an important precursor of long-term social and mental health problems. Social inclusion is a key policy driver and fits well within a new paradigm of health and well-being rather than illness-oriented services, yet little is known about social inclusion and its facilitators for "healthy" young people. We present a novel exploratory structural analysis of social inclusion using measures from 387 14- to 36-year-olds. Our model represents social inclusion as comprising social activity and community belonging, with both domains predicted by hopeful and dysfunctional self-beliefs but hopefulness more uniquely predicting social inclusion in adolescence. We conclude that social inclusion can be modeled for meaningful comparison across spectra of development, mental health, and functioning.

Impairment of perceptual metacognitive accuracy and reduced prefrontal grey matter volume in first-episode psychosis.

INTRODUCTION: Metacognition, or "thinking about thinking", is a higher-order thought process that allows for the evaluation of perceptual processes for accuracy. Metacognitive accuracy is associated with the grey matter volume (GMV) in the prefrontal cortex (PFC), an area also impacted in schizophrenia. The present study set out to investigate whether deficits in metacognitive accuracy are present in the early stages of psychosis. METHODS: Metacognitive accuracy in first-episode psychosis (FEP) was assessed on a perceptual decision-making task and their performance compared to matched healthy control participants (N = 18). A novel signal detection theory approach was used to model metacognitive sensitivity independently from objective perceptual performance. A voxel-based morphometry investigation was also conducted on GMV. RESULTS: We found that the FEP group demonstrated significantly worse metacognitive accuracy compared to controls (p = .039). Importantly, GMV deficits were also observed in the superior frontal gyrus. The findings suggest a specific deficit in this processing domain to exist at first episode; however, no relationship was found between GMV and metacognitive accuracy. CONCLUSIONS: Our findings support the notion that an inability to accurately scrutinise perception may underpin functional deficits observed in later schizophrenia; however, the exact neural basis of metacognitive deficits in FEP remains elusive.

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT).

BACKGROUND: People with psychosis have a reduced life expectancy of 10-20 years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. METHODS: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. RESULTS: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15 months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p = 0.034). The 22% of patients who received >180 min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. CONCLUSION: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. TRIAL REGISTRATION: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926 .

Randomised controlled trial to improve health and reduce substance use in established psychosis (IMPaCT): cost-effectiveness of integrated psychosocial health promotion.

BACKGROUND: There is mounting evidence that people with severe mental illness have unhealthy lifestyles, high rates of cardiovascular and metabolic diseases, and greater risk of early mortality. This study aimed to assess the cost-effectiveness of a health promotion intervention seeking to improve physical health and reduce substance use in people with psychosis. METHODS: Participants with a psychotic disorder, aged 18-65 years old and registered on an enhanced care approach programme or equivalent were recruited from community mental health teams in six mental health trusts in England. Participants were randomisation to either standard community mental health team care (treatment as usual) or treatment as usual with an integrated health promotion intervention (IMPaCT). Cost-effectiveness and cost-utility analyses from health and social care and societal perspectives were conducted alongside a cluster randomised controlled trial. Total health and social care costs and total societal costs at 12 and 15 months were calculated as well as cost-effectiveness (incremental cost-effectiveness ratios and cost-effectiveness acceptability curves) at 15 months based on quality of life (SF-36 mental and physical health components, primary outcome measures) and quality adjusted life years (QALYs) using two measures, EQ-5D-3 L and SF-36. Data were analysed using bootstrapped regressions with covariates for relevant baseline variables. RESULTS: At 12-15 months 301 participants had full data needed to be included in the economic evaluation. There were no differences in adjusted health and social care costs (£95, 95% CI -£1410 to £1599) or societal costs (£675, 95% CI -£1039 to £2388) between the intervention and control arms. Similarly, there were no differences between the groups in the SF-36 mental component (-0.80, 95% CI -3.66 to 2.06), SF-36 physical component (-0.68, 95% CI -3.01 to 1.65), QALYs estimated from the SF-36 (-0.00, -0.01 to 0.00) or QALYs estimated from the EQ-5D-3 L (0.00, 95% CI -0.01 to 0.02). Cost-effectiveness acceptability curves for all four outcomes and from both cost perspectives indicate that the probability of the health promotion intervention being cost-effective does not exceed 0.4 for willingness to pay thresholds ranging from £0-£50,000. CONCLUSIONS: Alongside no evidence of additional quality of life/clinical benefit, there is also no evidence of cost-effectiveness. TRIAL REGISTRATION: ISRCTN58667926 . Date retrospectively registered: 23/04/2010. Recruitment start date: 01/03/2010.

Self-reflection and set-shifting mediate awareness in cognitively preserved schizophrenia patients.

BACKGROUND: Poor insight in schizophrenia has been linked to poor cognitive functioning, psychological processes such as denial, or more recently with impaired metacognitive capacity. Few studies, however, have investigated the potential co-dependency of multiple factors in determining level of insight, but such a model is necessary in order to account for patients with good cognitive functioning who have very poor awareness. As evidence suggests that set-shifting and cognitive insight (self-reflection (SR) and self-certainty) are strong predictors of awareness we proposed that these factors are key mediators in the relationship between cognition and awareness. We hypothesised that deficits specifically in SR and set-shifting determine level of awareness in the context of good cognition. METHODS: Thirty schizophrenia patients were stratified by high and low awareness of illness and executive functioning scores. Cognitive insight, cognition, mood and symptom measures were compared between sub-groups. RESULTS: A low insight/high executive functioning (LI-HE) group, a high insight/high executive functioning (HI-HE) group and a low insight/low executive functioning (LI-LE) group were revealed. As anticipated, the LI-HE patients showed significantly lower capacity for SR and set-shifting than the HI-HE patients. CONCLUSIONS: This study indicates that good cognitive functioning is necessary but not sufficient for good awareness; good awareness specifically demands preserved capacity to self-reflect and shift-set. Results support Nelson and Narens' [1990. Metamemory: A theoretical framework and new findings. The Psychology of Learning and Motivation, 26, 125-173] model of metacognition by which awareness is founded on control (set-shifting) and monitoring (SR) processes. These specific factors could be targeted to improve insight in patients with otherwise unimpaired cognitive function.

Communications to children about mental illness and their role in stigma development: an integrative review.

BACKGROUND: Limited literature on the stigma of mental illness has examined the socio-cultural processes involved in the development of stigma around mental health in children, which emerges in mid-childhood (7-11 years). Greater understanding might inform preventative interventions. AIMS: This review aims to integrate disparate theoretical and empirical research to provide an overview of social communications to children aged 7--11 years about mental illness and their role in the development of stigmatised views. Four key socio-cultural contexts (the media, school, peers, parents) of relevance to children's development will be considered. METHOD: Systematic literature searches were conducted within electronic databases and abstracts were scanned to identify relevant studies. Fifteen papers were selected for the review. RESULTS: The review found few studies have directly examined communications about mental illness to children. Available evidence suggests messages across children's socio-cultural contexts are characterised by silence and stigma, which may shape children's developing views. Specific theoretical frameworks are lacking; possible mechanisms of transmission are discussed. CONCLUSIONS: This review suggests overcoming stigma will require efforts targeting young children, explicitly tackling mental illness, and spanning multiple social spheres: further research is warranted.

Structural insights into the role of the cyclic backbone in a squash trypsin inhibitor.

MCoTI-II is a head-to-tail cyclic peptide with potent trypsin inhibitory activity and, on the basis of its exceptional proteolytic stability, is a valuable template for the design of novel drug leads. Insights into inhibitor dynamics and interactions with biological targets are critical for drug design studies, particularly for protease targets. Here, we show that the cyclization and active site loops of MCoTI-II are flexible in solution, but when bound to trypsin, the active site loop converges to a single well defined conformation. This finding of reduced flexibility on binding is in contrast to a recent study on the homologous peptide MCoTI-I, which suggested that regions of the peptide are more flexible upon binding to trypsin. We provide a possible explanation for this discrepancy based on degradation of the complex over time. Our study also unexpectedly shows that the cyclization loop, not present in acyclic homologues, facilitates potent trypsin inhibitory activity by engaging in direct binding interactions with trypsin.

Understanding the Mechanisms of Cognitive Remediation on Recovery in People With Early Psychosis: A Mediation and Moderation Analysis.

BACKGROUND: To provide precision cognitive remediation therapy (CR) for schizophrenia, we need to understand whether the mechanism for improved functioning is via cognition improvements. This mechanism has not been rigorously tested for potential moderator effects. STUDY DESIGN: We used data (n = 377) from a randomized controlled trial using CIRCuiTS, a therapist-supported CR, with participants from first-episode psychosis services. We applied structured equation modeling to test whether: (1) CR hours explain the goal attainment functional outcome (GAS) at posttreatment, (2) global cognitive improvement mediates GAS, and if (3) total symptoms moderate the CR hours to cognitive improvement pathway, and/or negative symptoms moderate the cognition to functioning pathway, testing moderator effects via the mediator or directly on CR hours to functioning path. STUDY RESULTS: CR produced significant functioning benefit for each therapy hour (Coeff = 0.203, 95% CI 0.101-0.304, P < .001). The mediated path from CR hours to cognition and cognition to functioning was small and nonsignificant (Coeff = 0.014, 95% CI = -0.010, 0.037, P = .256). Total symptoms did not moderate the path to cognition (P = .211) or the direct path to outcome (P = .896). However, negative symptoms significantly moderated the effect of cognitive improvements on functioning (P = .015) with high negative symptoms reducing the functional gains of improved cognition. CONCLUSIONS: Although cognitive improvements were correlated with functioning benefit, they did not fully explain the positive effect of increased therapy hours on functioning, suggesting additional CR factors also contribute to therapy benefit. Negative symptoms interfere with the translation of cognitive improvements into functional gains so need consideration.