RSS 1.0Psychosis and Schizophrenia
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Olanzapine-induced pedal oedema with delayed resolution: A case report and review of literatureOlanzapine can have a better impact on negative symptoms of schizophrenia with reduced motor side effects compared to other atypical antipsychotics, according to some literature. Here, the authors describe a case of a woman with a diagnosis of schizophrenia who developed the rare side effect of bilateral pedal oedema while on oral olanzapine. The possible mechanism behind the condition and the clinical management measures taken to resolve the oedema is discussed. Copyright © 2024 John Wiley & Sons, Ltd.
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Quantifying the core deficit in classical schizophreniaIn the classical descriptions of schizophrenia, Kraepelin and Bleuler recognized disorganization and impoverishment of mental activity as fundamental symptoms. Their classical descriptions also included a tendency to persisting disability. The psychopathological processes underlying persisting disability in schizophrenia remain poorly understood. The delineation of a core deficit underlying persisting disability would be of value in predicting outcome and enhancing treatment. We tested the hypothesis that mental disorganization and impoverishment are associated with persisting impairments of cognition and role function, and together reflect a latent core deficit that is discernible in cases diagnosed by modern criteria. We used Confirmatory Factor Analysis to determine whether measures of disorganization, mental impoverishment, impaired cognition, and role functioning in 40 patients with schizophrenia represent a single latent variable. Disorganization scores were computed from the variance shared between disorganization measures from 3 commonly used symptom scales. Mental impoverishment scores were computed similarly. A single factor model exhibited a good fit, supporting the hypothesis that these measures reflect a core deficit. Persisting brain disorders are associated with a reduction in post-movement beta rebound (PMBR), the characteristic increase in electrophysiological beta amplitude that follows a motor response. Patients had significantly reduced PMBR compared with healthy controls. PMBR was negatively correlated with core deficit score. While the symptoms constituting impoverished and disorganized mental activity are dissociable in schizophrenia, nonetheless, the variance that these 2 symptom domains share with impaired cognition and role function, appears to reflect a pathophysiological process that might be described as the core deficit of classical schizophrenia. Copyright © The Author(s) 2020. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.
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Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with psychosis experience (NEON Trial): A pragmatic randomised controlled trialBACKGROUND: The Narrative Experiences Online (NEON) Intervention provides self-managed web-based access to mental health recovery narratives (n = 659). We evaluated effectiveness and cost-effectiveness in improving quality of life for adults resident in England with mental health problems and recent psychosis experience. METHODS: Prospectively registered pragmatic parallel-group randomised trial controlling for usual care, recruiting from statutory mental health services and through community engagement activities, with a 52-week primary endpoint (ISRCTN11152837). All trial procedures and the NEON Intervention were delivered by an integrated web-application. Randomisation was through an independently generated list (no stratification). Allocation was masked for statistical staff and the Chief Investigator but not participants. Intervention arm participants received immediate NEON Intervention access. Control arm participants received access after completing primary endpoint questionnaires. The primary outcome was quality of life through the Manchester Short Assessment (MANSA). Serious Adverse Events (SAEs) were collected through web-based safety report forms and identified from health service usage data. The primary analysis was by a prospectively described Intention To Treat principle excluding participants who had registered multiple times, with multiple imputation for missing data. FINDINGS: Between 9 March 2020 and 1 March 2021, 739 participants were randomised (intervention:370; control: 369), providing more than 90% power to detect a baseline-adjusted difference of 0.25 in the MANSA score. Mean age was 34.8 years (standard deviation (SD) 12.0), 561 (75.9%) were white British, 443 (59.9%) were female, 609 (82.4%) had accessed specialist care mental health services, and 698 (94.5%) had accessed primary care mental health services. Mean baseline MANSA score was 3.7 for control and intervention arms (SD 0.9 and 1.0). 565 (76.5%) participants provided primary endpoint MANSA data with a mean score of 4.1 (SD 1.0) for both arms. We found no significant difference in Quality of Life between the two arms at the primary endpoint (baseline-adjusted difference 0.07, 95% CI -0.07 to 0.21, p = 0.35). The incremental cost-effectiveness ratio (£110,501 per quality-adjusted life-year (QALY)) exceeded the prospectively defined cost-effectiveness threshold (£30,000 per QALY). 158 (42.8%) control arm and 194 (52.4%) intervention arm participants accessed narratives outside of the NEON Intervention. There were no related serious adverse events (SAEs). 116 unrelated SAEs were reported by control arm participants, and 107 by intervention arm participants. INTERPRETATION: Our findings do not indicate NEON Intervention access for all people with psychosis experience. Future research should consider a) evaluation with current mental health services users; b) optimisation to enable users to find hope-promoting narratives. FUNDING: National Institute for Health and Care Research (NIHR).
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Peer-led recovery groups for people with psychosis in South Africa (PRIZE): Results of a randomized controlled feasibility trialAIMS: The aims of this feasibility trial were to assess the acceptability and feasibility of peer-led recovery groups for people with psychosis in a low-resource South African setting, to assess the feasibility of trial methods, and to determine key parameters in preparation for a definitive trial. METHODS: The design was an individually randomised feasibility trial comparing recovery groups in addition to treatment as usual (TAU) with TAU alone. Ninety-two isiXhosa-speaking people with psychosis and forty-seven linked caregivers were recruited from primary care clinics and randomly allocated to trial arms in a 1:1 allocation ratio. TAU comprised anti-psychotic medication delivered in primary care. The intervention arm comprised six recovery groups including service users and caregivers. Two-hour recovery group sessions were delivered weekly in a 2-month auxiliary social worker (ASW)-led phase, then a 3-month peer-led phase. To explore acceptability and feasibility, a mixed methods process evaluation included 25 in-depth interviews and 2 focus group discussions at 5 months with service users, caregivers and implementers, and quantitative data collection including attendance and facilitator competence. To explore potential effectiveness, quantitative outcome data (functioning, relapse, unmet needs, personal recovery, stigma, health service use, medication adherence and caregiver burden) were collected at baseline, 2 months and 5 months post randomisation. Trial registration: PACTR202202482587686. RESULTS: Qualitative interviews revealed that recovery groups were broadly acceptable with most participants finding groups to be an enjoyable opportunity for social interaction, and joint problem-solving. Peer facilitation was a positive experience; however a minority of participants did not value expertise by lived experience to the same degree as expertise of professional facilitators. Attendance was moderate in the ASW-led phase (participants attended 59% sessions on average) and decreased in the peer-led phase (41% on average). Participants desired a greater focus on productive activities and financial security. Recovery groups appeared to positively impact on relapse. Relapse occurred in 1 (2.2%) of 46 participants in the recovery group arm compared to 8 (17.4%) of 46 participants in the control arm (risk difference -0.15 [95% CI: -0.26; -0.05]). Recovery groups also impacted on the number of days in the last month totally unable to work (mean 1.4 days recovery groups vs 7.7 days control; adjusted mean difference -6.3 [95%CI: -12.2; -0.3]). There were no effects on other outcomes. CONCLUSION: Peer-led recovery groups for people with psychosis in South Africa are potentially acceptable, feasible and effective. A larger trial, incorporating amendments such as increased support for peer facilitators, is needed to demonstrate intervention effectiveness definitively.
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Defining the disturbance in cortical glutamate and GABA function in psychosis and its origins and consequences [In Press]It is widely thought that the onset of psychotic symptoms in schizophrenia may arise from an early neurotoxic phase, possibly related to oxidative stress or inflammation, and a late residual damage phase associated with persistent negative symptoms. We tested this hypothesis in a 3-centre study using magnetic resonance spectroscopy (MRS) to determine whether abnormalities in glutamate, glutamine and GABA content in anterior cingulate cortex (ACC) differed between people with minimally treated ‘Recent’ onset schizophrenia and an ‘Established’ group with > 10 years of treatment. We tested whether neurochemical abnormalities were i) mediated by raised circulating inflammatory cytokine concentrations, c-reactive protein (CRP) and interleukin-6 (IL-6), or depletion of glutathione and ii) associated with ratings of positive and negative symptoms. Relative to age-matched controls, the Established group showed significantly greater reduction in ACC glutamate than the Recent group, which did not differ from controls. This effect was not attributable to antipsychotic drug exposure. Patient ACC glutathione was negatively correlated with age. IL-6 was increased in both clinical groups, while increases in CRP were greater in the Established than Recent group. Elevated CRP was entirely accounted for by greater antipsychotic drug exposure and BMI, while residual elevation in IL-6 in the Established group did not account for their lower ACC glutamate. GABA was reduced relative to controls across ACC and occipital voxels. This reduction was not associated with drug treatment, BMI or cytokine levels. Only ACC GABA content correlated significantly with symptoms, lower content with greater positive and negative symptoms across both groups.
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A protocol to assess antipsychotics prescribing and physical health monitoring in children and young people: A cohort study using primary care data from QResearch [in press]Antipsychotic medicines are prescribed to children and young people (CYP) with mental health conditions such as schizophrenia, bipolar disorder, behavioural disorders, autism spectrum disorder and tics. The physical side effects of these medicines require monitoring, and this responsibility can be transferred to primary care. This study will describe the trends in antipsychotic prescribing in CYP, identify the mental health conditions, symptoms and comorbidities associated with the prescriptions, and determine the extent of physical health monitoring in primary care both for CYP prescribed antipsychotics and those with mental health conditions without antipsychotic prescriptions. The study will use data from QResearch, a large, anonymised, UK primary care electronic health record database. Records will be linked to secondary care data from hospital episode statistics and socioeconomic deprivation information. People aged 5 to 17 years, who are registered with GPs in England contributing to QResearch between 1 January 2006 and 31 July 2021 will be included. Incidence and prevalence rates will be calculated over the study period, and Poisson regression will be used to estimate incidence rate ratios. Results from this study will identify where improvements to clinical practice or to treatment guidelines may be needed.
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Probing the biological underpinnings of advanced brain ageing in schizophrenia [in press]Background: Recent evidence suggests that patients with schizophrenia may show advanced brain ageing, particularly evident after the first year of onset. However, it is unclear if accelerated ageing relents, persists or continues to increase over time. The underlying causal factors are also poorly understood. Disruptions in glutamate function, oxidative stress, and inflammation may all contribute to progressive brain changes in people with schizophrenia. We examine whether brain ageing differs between early and established stages of schizophrenia, correlates with symptom severity and varies with markers of brain function, oxidative status and inflammatory burden.
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Psychosis following phenibut-assisted withdrawalPhenibut is less frequently used in the UK compared with heroin, cocaine, crack, cannabis, ketamine or alcohol but is currently not covered by the UK drugs legislation. It is widely available on the internet, and its popularity is increasing, particularly among younger, internet-savvy patients. This case describes a patient who developed psychosis during medically assisted withdrawal from phenibut. Copyright © 2024 Wiley Interface Ltd.
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The mechanisms of persisting disability in schizophrenia: Imprecise predictive coding via cortico-striatal-thalamo-cortical loop dysfunctionPersisting symptoms and disability remain a problem for an appreciable proportion of people with schizophrenia despite treatment with antipsychotic medication. Improving outcomes requires an understanding of the nature and mechanisms of the pathological processes underlying persistence. Classical features of schizophrenia, which include disorganization and impoverishment of mental activity, are well recognised early clinical features that predict poor long-term outcome. Substantial evidence indicates that these features reflect imprecise predictive coding. Predictive coding provides an over-arching framework for understanding efficient function of the nervous system. Imprecise predictive coding also has the potential to precipitate acute psychosis characterised by reality distortion (delusions and hallucinations) at times of stress. On the other hand, substantial evidence indicates that persistent reality distortion itself gives rise to poor occupational and social function in the long term. Furthermore, abuse of psychotomimetic drugs, which exacerbate reality distortion, contributes to poor long-term outcome in schizophrenia. Neural circuits involved in modulating volitional acts are well understood to be implicated in addiction. Plastic changes in these circuits may account for the association between psychotomimetic drug abuse and poor outcomes in schizophrenia. We propose a mechanistic model according to which unbalanced inputs to the corpus striatum disturb the precision of sub-cortical modulation of cortical activity supporting volitional action. This model accounts for the evidence that early classical symptoms predict poor outcome, while in some circumstances, persistent reality distortion also predicts poor outcome. This model has implications for the development of novel treatments that address the risk of persisting symptoms and disabilities in schizophrenia.
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Healing Houses systematic review: Design, sustainability, opportunities and barriers facing Soteria and peer respite developmentBACKGROUND: Soteria houses and peer respites, collectively called Healing Houses, are alternatives to psychiatric hospitalisation. AIMS: The aim of this research is to review Healing Houses in relation to design characteristics (architectural and service), sustainability and development opportunities and barriers. METHODS: This systematic review followed a PROSPERO protocol (CRD42022378089). Articles were identified from journal database searches, hand searching websites, Google Scholar searches, expert consultation and backwards and forward citation searches. RESULTS: Eight hundred and forty-nine documents were screened in three languages (English, German and Hebrew) and 45 documents were included from seven countries. The review highlights 11 architectural design characteristics (atmosphere, size, soft room, history, location, outdoor space, cleanliness, interior design, facilities, staff only areas and accessibility), six service design characteristics (guiding principles, living and working together, consensual treatment, staff, supporting personal meaning making and power), five opportunities (outcomes, human rights, economics, hospitalization and underserved) and four types of barriers (clinical, economic and regulatory, societal and ideological). The primary sustainability issue was long-term funding. CONCLUSION: Future research should focus on operationalizing a "home-like" atmosphere and the impact of design features such as green spaces on wellbeing of staff and service users. Future research could also produce design guidelines for Healing Houses.
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Tardive dyskinesia with antipsychotic medication in children and adolescents: A systematic literature reviewBACKGROUND: Tardive dyskinesia (TD) is a persisting, and potentially irreversible, movement disorder associated with treatment with dopamine receptor antagonists. Few data are available on the risk of TD in children and adolescents treated with antipsychotic medication. OBJECTIVE: To review the literature on incidence, risk factors, and treatment options for antipsychotic-associated TD in children and adolescents (aged < 18 years). METHODS: Relevant articles were identified through a systematic search of Embase and Medline performed in January 2024. Methodological quality was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute Critical Appraisal tools. RESULTS: Thirteen studies were identified. The reported TD point prevalence was 5-20%, with higher rates in studies involving typical antipsychotics. Lower estimates (around 1%) emerged from analyses of clinical database data suggesting underdiagnosis in clinical practice. Risk factors included treatment with typical antipsychotics, higher doses, longer duration of exposure, older age, female gender, higher baseline Abnormal Involuntary Movements Scale (AIMS) scores, intellectual impairment, and perinatal complications. CONCLUSION: Although relatively few cases have been reported in children and adolescents, TD remains a risk in this population. Individuals receiving antipsychotics should be monitored carefully for the emergence of abnormal movements. Other than dose reduction, discontinuation, or switch to a lower-risk antipsychotic, few interventions have demonstrated efficacy. The strongest evidence for pharmacological treatment is for VMAT-2 inhibitors (valbenazine and deutetrabenazine), but these drugs are not licensed for use in children. To reduce risk, antipsychotics should be prescribed only if necessary, at the minimum effective dose and for the minimum necessary duration.
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Identification of youth at clinical high-risk for psychosis: A community-based study from IndiaAIM: A two-stage process, wherein self-report screening precedes the structured interview, is suggested for identifying individuals at clinical high-risk for psychosis (CHR-P) in community samples. Aim of this study was to screen a community youth sample from India for CHR-P using the two-stage method. Specific objectives were to assess concordant validity of the self-report measure and predictive validity of the two-stage method. METHODS: Based on probability sampling, 2025 youth aged 15-24 years were recruited from one rural and one urban area of Telangana, a Telugu-speaking state in India. Telugu version of the PRIME Screen-Revised (PS-R) and structured interview for psychosis-risk syndromes (SIPS) were used. CHR-P positive and negative cohorts were followed-up for transition to psychosis at 3-monthly intervals. RESULTS: One hundred ten individuals screened positive on PS-R. SIPS conducted on 67 out of 110 individuals confirmed 62 (92.54%) to be CHR-P positive. PS-R showed 98.41% sensitivity and 90.74% specificity. Among CHR-P positive, three participants transitioned to psychosis in 15 months. The hazard ratio for psychosis transition was 11.4. CONCLUSIONS: Screening accuracy of PS-R in the community youth sample in Telangana is optimum. The hazard ratio for psychosis transition in the community identified CHR-P indicates good predictive validity for the two-stage method.
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Patients with psychotic disorders are more likely to refuse vaccination: An audit of vaccine acceptability on acute adult psychiatric wardsAims. This audit is looking at COVID-19 vaccine uptake in an acute adult psychiatric setting as part of the national drive to minimize COVID-19 infection. The aims of this audit are to identify: the number of patients that have been offered vaccination in a ward setting; the acceptability of the vaccination and the reasons for non-acceptance of vaccine. Methods. A total of 339 patients were admitted to acute adult psychiatric wards (Male, Female, PICU) at Highbury Hospital, Nottingham between February to August 2021. Data on the following parameters: demographics (age, sex, ethnicity), section status, HoNOS cluster, admission length and vaccine data (offered, accepted, received) using the RIO system and Health Informatics. Results. Out of 339 patients, 31% (n = 105) had received or planned to receive the first dose of vaccine prior to admission. 43% (n = 100) of 234 patients who hadn't received vaccine were offered. Out of the patients who were offered vaccine, 59% (n = 59) accepted. 92% (n = 55) of patients who accepted vaccine, received vaccine. Those offered vaccination had an average length of stay of 117 days whilst those not offered had a shorter average length of stay of 81 days. For patients who were offered vaccine, those who were sectioned and in psychotic clusters refused vaccine compared to nonpsychotic and informal patients. Deprivation, gender, age, admission length had no statistical significance in vaccine uptake for patients who were offered. Patients listed the following reasons for refusing the vaccine: media distrust; vaccine not effective; already had COVID-19; doesn't want it; believes vaccine made by consultant; doesn't want bad reaction; Scientists and politicians are liars ; I am fine and don't need it'; Don't trust it and don't like needles ; Don't want to be part of the game ; Have had covid twice and, if I get it, I'd prefer my body to fight it . Conclusion. Our current vaccine acceptance rate of 59% is lower than those found nationally (80%) and in a medium secure psychiatric hospital (77%). The trust policy recommends all eligible patients should be offered the vaccine; our offer rate is lower than this standard. The low offer rate may be explained by vaccines being offered in rounds leading to patients possibly being missed. Our acceptance rate could be enhanced by improving our vaccination care plans for formally admitted psychotic patients.
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Using electronic health records to facilitate precision psychiatryThe use of clinical prediction models to produce individualised risk estimates can facilitate the implementation of precision psychiatry. As a source of data from large, clinically representative patient samples, electronic health records (EHRs) provide a platform to develop and validate clinical prediction models, as well as potentially implementing them in routine clinical care. The present review describes promising use cases for the application of precision psychiatry to EHR data and considers their performance in terms of discrimination (ability to separate individuals with and without the outcome) and calibration (extent to which predicted risk estimates correspond to observed outcomes), as well as their potential clinical utility (weighing benefits and costs associated with the model compared to different approaches across different assumptions of the number-needed-to-test). We review four externally validated clinical prediction models designed to predict, respectively: psychosis onset, psychotic relapse, cardiometabolic morbidity, and suicide risk. We then discuss the prospects for clinically implementing these models, and the potential added value of integrating data from evidence syntheses, standardised psychometric assessments, and biological data into EHRs. Clinical prediction models can utilise routinely collected EHR data in an innovative way, representing a unique opportunity to inform real-world clinical decision making. Combining data from other sources (e.g. meta-analyses) or enhancing EHR data with information from research studies (clinical and biomarker data) may enhance our abilities to improve performance of clinical prediction models.
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A good life with psychosis: Rate of positive outcomes in first-episode psychosis at 10-year follow-upBACKGROUND: More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. METHODS: FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). RESULTS: In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ(2)). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. CONCLUSIONS: In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment.
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Approaches and challenges to assessing risk of violence in first episode psychosis: A qualitative interview study of clinicians, patients and carersAIM: Clinical services for early psychosis seek to improve prognosis for a range of adverse outcomes. For some individuals, perpetration of violence is an important potential outcome to reduce. How these clinical services currently assess this risk however is uncertain. This study aimed to address this gap by using qualitative methods to examine in depth current approaches, attitudes and challenges to assessing violence risk in this clinical setting, from the perspectives of multidisciplinary clinicians, patients and carers. METHODS: Participants were recruited from two UK Early Intervention in Psychosis services. Semi-structured individual interviews were undertaken using a topic guide. In addition, clinical vignettes were presented to clinician participants as a probe to prompt discussion. Data were analysed using thematic analysis, informed by the constant comparative method. RESULTS: We conducted 30 qualitative interviews, of 18 clinicians and 12 patients and carers. Themes developed from clinician interviews included key difficulties of low confidence, limited training, accessing collateral information and variation in how risk is appraised and communicated. Potential stigma and sensitivity of the topic of violence were perceived as barriers to its discussion. Patient and carer perspectives provided insight into how to address barriers, and highlighted the importance of an open approach, including with families. CONCLUSIONS: We recommend developing contextually appropriate pathways to collaboratively assess violence risk and identify modifiable needs to reduce this risk, and for practical improvements in training and information-sharing.
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Violence in schizophrenia: Triangulating the evidence on perpetration riskNo abstract available
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Second-generation antipsychotics and metabolic syndrome: A role for mitochondriaPsychosis is a known risk factor for developing metabolic syndrome (MetS). The risk is even greater in patients who are taking second-generation antipsychotics (SGAs). SGAs exacerbate metabolic abnormalities and lead to a 3-fold increased risk of severe weight gain, type 2 diabetes, and cardiovascular disease in patients. Mitochondrial dysfunction is a hallmark of MetS. Mitochondria process glucose and fatty acids into ATP. If these processes are impaired, it can result in dyslipidaemia, hyperglycaemia and an imbalance between nutrient input and energy output. This leads to increased adiposity, insulin resistance and atherosclerosis. It is unclear how SGAs induce MetS and how mitochondria might be involved in this process. It has been found that SGAs impair cellular glucose uptake in liver, dysregulating glucose and fatty acid metabolism which leads to an accumulation of glucose and/or lipids and an increase reactive oxygen species (ROS) which target mitochondrial proteins. This affects complexes of the electron transport chain (ETC) to reduce mitochondrial respiration. While there is a suggestion that SGAs may interact with a variety of processes that disrupt mitochondrial function, some of the results are conflicting, and a clear picture of how SGAs interact with mitochondria in different cell types has not yet emerged. Here, we outline the current evidence showing how SGAs may trigger mitochondrial dysfunction and lead to the development of MetS.
