RSS 1.0Psychosis and Schizophrenia
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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.
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Neurobiology of psychosis and schizophrenia 2022: Nottingham meetingNo abstract available
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Antidepressants for the prevention of depression following first-episode psychosis (ADEPP): Study protocol for a multi-centre, double-blind, randomised controlled trialBACKGROUND: Depressive episodes are common after first-episode psychosis (FEP), affecting more than 40% of people, adding to individual burden, poor outcomes, and healthcare costs. If the risks of developing depression were lower, this could have a beneficial effect on morbidity and mortality, as well as improving outcomes. Sertraline is a selective serotonin reuptake inhibitor and a common first-line medication for the treatment of depression in adults. It has been shown to be safe when co-prescribed with antipsychotic medication, and there is evidence that it is an effective treatment for depression in established schizophrenia. We present a protocol for a multi-centre, double-blind, randomised, placebo-controlled clinical trial called ADEPP that aims to investigate the efficacy and cost-effectiveness of sertraline in preventing depression after FEP. METHODS: The recruitment target is 452 participants between the ages of 18 and 65 years who are within 12 months of treatment initiation for FEP. Having provided informed consent, participants will be randomised to receive either 50 mg of sertraline daily or matched placebo for 6 months, in addition to treatment as usual. The primary outcome measure will be a comparison of the number of new cases of depression between the treatment and placebo arms over the 6-month intervention phase. Secondary outcomes include suicidal behaviour, anxiety, rates of relapse, functional outcome, quality of life, and resource use. DISCUSSION: The ADEPP trial will test whether the addition of sertraline following FEP is a clinically useful, acceptable, and cost-effective way of improving outcomes following FEP. TRIAL REGISTRATION: ISRCTN12682719 registration date 24/11/2020.
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Structural and functional brain patterns predict formal thought disorder's severity and its persistence in recent-onset psychosis: Results from the PRONIA StudyBACKGROUND: Formal thought disorder (FThD) is a core feature of psychosis, and its severity and long-term persistence relates to poor clinical outcomes. However, advances in developing early recognition and management tools for FThD are hindered by a lack of insight into the brain-level predictors of FThD states and progression at the individual level. METHODS: 233 individuals with recent-onset psychosis were drawn from the multi-site European Prognostic Tools for Early Psychosis Management study. Support vector machine classifiers were trained within a cross-validation framework to separate two FThD symptom-based subgroups (high vs. low FThD severity), using cross-sectional whole-brain multi-band fractional amplitude of low frequency fluctuations (fALFF), gray-matter volume (GMV) and white-matter volume (WMV) data. Moreover, we trained machine learning models on these neuroimaging readouts to predict the persistence of high FThD subgroup membership from baseline to 1-year follow-up. RESULTS: Cross-sectionally, multivariate patterns of GMV within the salience, dorsal attention, visual and ventral attention networks separated the FThD severity subgroups (BAC=60.8%). Longitudinally, distributed activations/deactivations within all fALFF sub-bands (BAC(slow-5)=73.2%, BAC(slow-4)=72.9%, BAC(slow-3)=68.0), GMV patterns overlapping with the cross-sectional ones (BAC=62.7%) and smaller frontal WMV (BAC=73.1%) predicted the persistence of high FThD severity from baseline to follow-up, with a combined multi-modal balanced accuracy of BAC=77%. CONCLUSIONS: We report first evidence of brain structural and functional patterns predictive of FThD severity and persistence in early psychosis. These findings open the avenue for the development of neuroimaging-based diagnostic, prognostic and treatment options for the early recognition and management of FThD and associated poor outcomes.
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An umbrella review of adverse effects associated with antipsychotic medications: The need for complementary study designsAntipsychotic medications are widely prescribed in psychotic illnesses and other mental disorders. Effectiveness is well-established, particularly for reducing symptoms such as delusions and hallucinations, but can be impacted by tolerability. Adverse effects are wide-ranging, and vary between antipsychotics, which is clinically important. This umbrella review aimed to comprehensively summarise the extent and quality of evidence for adverse effects associated with antipsychotic use in people with mental disorders. We included 32 meta-analyses of randomised trials and observational studies. The overall robustness of reported associations was considered in terms of review quality, heterogeneity, excess significance bias, and prediction intervals. Using this approach, endocrine and metabolic, movement-related, sedation and sleep problems were the clinical domains with strongest evidence. The overall quality of included meta-analyses was low, and individual adverse effects were not typically examined in meta-analyses of both randomised and observational study designs. Future reviews should focus on adhering to methodological guidelines, consider the complementary strengths of different study designs, and integrate clinically relevant information on absolute rates and severity of adverse effects.
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The relationship between sleep and suicidality in schizophrenia spectrum and other psychotic disorders: A systematic reviewIndividuals with Schizophrenia Spectrum Disorders (SSDs) have significantly higher rates of suicidal thoughts, attempts, and death by suicide in comparison to the general population. Sleep disturbances (reduced duration, timing and quality of sleep) are risk factors for suicidality in the general population, with research indicating the relationship is both immediate and accumulative. Sleep disturbances are also considered to be implicated in the onset and exacerbation of psychotic symptoms in SSDs. Reducing the risk of suicidality in SSDs remains an important public health priority, thus exploration of contributing risk factors is warranted. Sleep monitoring may also offer an adjunct risk monitoring method to suicidality assessments in SSDs, and a potential treatment target for psychotic symptoms. This review aimed to explore proximal and longitudinal relationships between self-reported and objectively measured sleep and suicidality in SSDs and other psychotic disorders. A comprehensive search of four databases was conducted. Eleven studies met the inclusion criteria (10 cross sectional and 1 longitudinal). Narrative synthesis indicated that self-reported sleep disturbances and sleep disorders (e.g. insomnia) were associated with increased risk of suicidal ideation and attempt. However, one study employing polysomnography did not find sleep to be associated with suicidality. Methodological limitations of the evidence base include: i) little experimental or longitudinal evidence, (ii) self-report and/or single item assessment of sleep disturbance, (iii) limited use of validated measures of suicidality, (iv) considerable research in long-term schizophrenia but sparse evidence in early psychosis. Future research should explore (i) cross-sectional and longitudinal relationships between specific aspects of suicidality and objective sleep parameters, (ii) use qualitative or mixed-methods designs to disentangle the nuances and bidirectionality in the sleep-suicide relationship, (iii) explore the psychological processes underpinning or mediating the sleep-suicide relationship in SSDs.
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Measurement of brain glutathione with magnetic resonance spectroscopy in schizophrenia-spectrum disorders - A systematic review and meta-analysisOxidative stress may contribute to declining course and poor outcomes in psychosis. However, in vivo Magnetic Resonance Spectroscopy studies yield disparate results due to clinical stage, sample demographics, neuroanatomical focus, sample size, and acquisition method variations. We investigated glutathione in brain regions from participants with psychosis, and the relation of glutathione to clinical features and spectroscopy protocols. Meta-analysis comprised 21 studies. Glutathione levels did not differ between total psychosis patients (N = 639) and controls (N = 704) in the Medial Prefrontal region (k = 21, d = -0.09, CI = -0.28 to 0.10, p = 0.37). Patients with stable schizophrenia exhibited a small but significant glutathione reduction compared to controls (k = 14, d = -0.20, CI = -0.40 to -0.00, p = 0.05). Meta-regression showed older studies had greater glutathione reductions, possibly reflecting greater accuracy related to spectroscopy advancements in more recent studies. No significant effects of methodological variables, such as voxel size or echo time were found. Reduced glutathione in patients with stable established schizophrenia may provide novel targets for precision medicine. Standardizing MRS acquisition methods in future studies may help address discrepancies in glutathione levels.
