BACKGROUND: The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual\'s effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting.
METHODS: Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ9-THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ9-THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration.
RESULTS: CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (pcorr<0.05) but not 600 mg dosage. Declining AEA was observed with Δ9-THC at 10 mg (-1.3-fold) and 20 mg (-1.4-fold) but restored to baseline levels by 160 min. CBD+Δ9-THC yielded the highest increases in AEA (2.1-fold), OEA (1.9-fold) and PEA (1.8-fold) without reaching a maximal response.
CONCLUSIONS: CBD-administered effects towards AEA, OEA and PEA are consistent with phase II trials reporting clinical improvement for acute schizophrenia (CBD≥800 mg). Including Δ9-THC appears to enhance the CBD-induced response towards AEA and its congeners. Our results warrant further investigations into the potential of these lipid-derived mediators as metabolic measures for CBD dose prescription and co-cannabinoid administration.

OBJECTIVE: Negative symptoms in schizophrenia are associated with significant illness burden. We sought to investigate clinical outcomes for patients with schizophrenia who present with predominant negative symptoms (PNS) vs without PNS.
METHODS: Retrospective analysis of electronic health record (EHR) data.
METHODS: 25 US providers of mental healthcare.
METHODS: 4444 adults with schizophrenia receiving care between 1999 and 2020.
METHODS: PNS defined as ≥3 negative symptoms and ≤3 positive symptoms recorded in EHR data at the time of the first recorded schizophrenia diagnosis (index date). Symptom data were ascertained using natural language processing applied to semistructured free text records documenting the mental state examination. A matched sample (1:1) of patients without PNS was used to compare outcomes. Follow-up data were obtained up to 12 months following the index date.
METHODS: Mean number of psychiatric hospital admissions.
METHODS: Mean number of outpatient visits, estimated treatment costs, Clinical Global Impression - Severity score and antipsychotic treatments (12 months before and after index date).
RESULTS: 360 (8%) patients had PNS and 4084 (92%) did not have PNS. Patients with PNS were younger (36.4 vs 39.7 years, p<0.001) with a greater prevalence of psychiatric comorbidities (schizoaffective disorders: 25.0 vs 18.4%, p=0.003; major depressive disorder: 17.8 vs 9.8%, p<0.001). During follow-up, patients with PNS had fewer days with an antipsychotic prescription (mean=111.8 vs 140.9 days, p<0.001). Compared with matched patients without PNS, patients with PNS were more likely to have a psychiatric inpatient hospitalisation (76.1% vs 59.7%, p<0.001) and had greater estimated inpatient costs ($16 893 vs $13 732, p=0.04).
CONCLUSIONS: Patients with PNS were younger and presented with greater illness severity and more psychiatric comorbidities compared with patients without PNS. Our findings highlight an unmet need for novel therapeutic approaches to address negative symptoms to improve clinical outcomes.

OBJECTIVE: To examine the relationship between schizophrenia, antipsychotic medication adherence and driver responsibility for motor vehicle crash.
METHODS: Retrospective observational cohort study using 20 years of population-based administrative health and driving data.
METHODS: British Columbia, Canada.
METHODS: Licensed drivers who were involved in a police-attended motor vehicle crash in British Columbia over a 17-year study interval (2000-16).
METHODS: Incident schizophrenia was identified using hospitalisation and physician services data. Antipsychotic adherence was estimated using prescription fill data to calculate the \'medication possession ratio\' (MPR) in the 30 days prior to crash.
METHODS: We deemed drivers \'responsible\' or \'non-responsible\' for their crash by applying a validated scoring tool to police-reported crash data. We used logistic regression to evaluate the association between crash responsibility and exposures of interest.
RESULTS: Our cohort included 808 432 drivers involved in a police-attended crash and for whom crash responsibility could be established. In total, 1689 of the 2551 drivers with schizophrenia and 432 430 of the 805 881 drivers without schizophrenia were deemed responsible for their crash, corresponding to a significant association between schizophrenia and crash responsibility (66.2% vs 53.7%; adjusted OR (aOR), 1.67; 95% CI, 1.53 to 1.82; p<0.001). The magnitude of this association was modest relative to established crash risk factors (eg, learner license, age ≥65 years, impairment at time of crash). Among the 1833 drivers with schizophrenia, near-optimal antipsychotic adherence (MPR ≥0.8) in the 30 days prior to crash was not associated with lower crash responsibility (aOR, 1.04; 95% CI, 0.83 to 1.30; p=0.55).
CONCLUSIONS: Crash-involved drivers with schizophrenia are more likely to be responsible for their crash, but the magnitude of risk is similar to socially acceptable risk factors such as older age or possession of a learner license. Contemporary driving restrictions for individuals with schizophrenia appear to adequately mitigate road risks, suggesting more stringent driving restrictions are not warranted.

暂无摘要。

BACKGROUND: Individuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor population representation, while there is only limited evidence from longitudinal studies on the role of anxiety, bipolar and psychotic disorders. Electronic health records (EHRs) permit large cohorts to be followed across the lifespan and include a wide range of diagnostic information.
OBJECTIVE: To assess the association between four groups of psychiatric disorders (schizophrenia, bipolar disorder/mania, depression and anxiety) with dementia in two large population-based samples with EHR.
METHODS: Using EHR on nearly 1 million adult individuals in Wales, and from 228 937 UK Biobank participants, we studied the relationships between schizophrenia, mania/bipolar disorder, depression, anxiety and subsequent risk of dementia.
RESULTS: In Secure Anonymised Information Linkage, there was a steep increase in the incidence of a first diagnosis of psychiatric disorder in the years prior to the diagnosis of dementia, reaching a peak in the year prior to dementia diagnosis for all psychiatric diagnoses. Psychiatric disorders, except anxiety, were highly significantly associated with a subsequent diagnosis of dementia: HRs=2.87, 2.80, 1.63 for schizophrenia, mania/bipolar disorder and depression, respectively. A similar pattern was found in the UK Biobank (HRs=4.46, 3.65, 2.39, respectively) and anxiety was also associated with dementia (HR=1.34). Increased risk of dementia was observed for all ages at onset of psychiatric diagnoses when these were divided into 10-year bins.
CONCLUSIONS: Psychiatric disorders are associated with an increased risk of subsequent dementia, with a greater risk of more severe disorders.
CONCLUSIONS: A late onset of psychiatric disorders should alert clinicians of possible incipient dementia.

BACKGROUND: Insomnia is a common symptom among patients with schizophrenia and schizoaffective disorder, negatively impacting symptom severity, functioning and well-being; however, it is rarely the direct focus of treatment. The main recommended treatment for insomnia is cognitive behavioural therapy (CBT-I). There is some evidence that CBT-I can also be used to treat insomnia in patients with schizophrenia, but only a few randomised controlled trials (RCTs) have been published. The aim of this ongoing RCT is to determine whether we can alleviate symptoms of insomnia and improve the quality of life in patients with schizophrenia and schizoaffective disorder through CBT-I delivered via the internet or in a group mode.
METHODS: The aim of this study is to recruit 84-120 outpatients from the Psychosis Clinics of Helsinki University Hospital and the City of Helsinki Health Services. The main inclusion criteria are a diagnosis of schizophrenia or schizoaffective disorder and self-reported sleep problems. The study will be performed on a cyclic basis, with a target of 12-24 patients per cycle. Participants are randomly assigned into three groups: (1) a group receiving only treatment as usual (TAU), (2) internet-based individual therapy for insomnia (iCBT-I)+TAU or (3) group therapy for insomnia (GCBT-I) conducted via a virtual platform+TAU. The primary outcome measures are quantitative changes in the Insomnia Severity Index score and/or changes in health-related quality of life using the 15D quality of life measure. Secondary outcomes include self-reported variables for sleep, health, stress and the severity of psychotic and depressive symptoms; objective outcomes include actigraphy and bed sensor data to evaluate circadian rhythms and motor activity. Outcome measures are assessed at baseline and after the treatment period at weeks 12, 24 and 36.
BACKGROUND: The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa, Finland, approved the study protocol. The results will be published in peer-reviewed journals.
BACKGROUND: NCT04144231.

BACKGROUND: Schizophrenia, a chronic mental problem, significantly impacts cognition, emotion and social functioning. Conventional pharmacotherapy faces challenges including numerous side effects, low adherence to medication and substantial costs. In this context, group arts therapies (GATs) emerge as a promising complementary approach for symptom alleviation in schizophrenia patients. Nonetheless, the effectiveness and safety of GATs are yet to be firmly established. This study aims to systematically assess the therapeutic impact of all group-based artistic interventions as complementary treatments for schizophrenia, focusing on their potential benefits.
METHODS: This study will search four English-language databases (PubMed, Web of Science, Cochrane Library and Embase), two Chinese databases (Wanfang Data and China National Knowledge Infrastructure) and three Korean databases (RISS, Korean Citation Index and DBpia) from their inception until October 2023. It will include all randomised controlled trials that compare GATs for schizophrenia with standard rehabilitation methods. The primary outcome is the improvement in patients\' positive and negative symptoms. Methodologies such as bias risk assessment, data synthesis, sensitivity analysis and subgroup analysis will be implemented using Review Manager V.5.4. Study results with high heterogeneity will be merged using a random-effects model (I 2>50% or p<0.1). In cases where meta-analysis is not viable due to significant clinical and methodological heterogeneity, a qualitative summary of the findings will be provided.
BACKGROUND: The data used in this systematic review are anonymised, devoid of any private information, eliminating the requirement for ethical approval. Dissemination of the research findings will be conducted via peer-reviewed publications.
UNASSIGNED: CRD42023471583.

BACKGROUND: Depressed mood is a psychological state characterised by sadness or loss of interest in activities. Depressed mood is a highly prevalent symptom across major mental disorders. However, there is limited understanding of the burden and management of comorbid depressed mood across major mental disorders. Therefore, this scoping review aims to summarise knowledge on depressed mood among persons with anxiety and/or psychosis. The specific aims are to describe the epidemiology and risk factors of depressed mood as a transdiagnostic target among persons with anxiety and/or psychosis, to identify commonly used outcome measures for depressed mood and to outline initial evidence of psychometric robustness and to identify and summarise the effectiveness of commonly applied depressed mood modification interventions. Our hope is that the proposed review will provide insights into the burden of depressed mood in persons with anxiety and psychosis and help to identify evidence gaps and recommendations for future research.
METHODS: This scoping review will be conducted per Arksey and O\'Malley\'s framework. We will first search for peer-reviewed articles and grey literature published from 2004 to 2023 in PubMed, Scopus, Web of Science, Africa-Wide Information, CINAHL, PsycINFO, Academic Search Premier, Humanities International Complete, Sabinet, SocINDEX, Open Grey and Google Scholar. We will include articles reporting depressed mood (subthreshold depression) among persons with anxiety and/or psychosis. Studies recruiting participants meeting depression diagnostic criteria and those published in non-English languages will be excluded. Two independent researchers will extract the data. We will analyse and chart data collaboratively with researchers with lived experiences of depressed mood.
BACKGROUND: This study does not require ethical approval as it is a literature review. The results will be submitted for publication in a peer-reviewed journal.

OBJECTIVE: Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer\'s disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.
METHODS: We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-β plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group.
RESULTS: No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aβ42 between patients with schizophrenia and controls found significantly decreased CSF Aβ42 in schizophrenia compared with controls. Hippocampal volume findings were mixed.
CONCLUSIONS: Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.

BACKGROUND: Most people with schizophrenia in China are supported by their family members in community. The patient\'s family is confronted with severe care burden and pressure, which directly affects the caregiver\'s own health and social life, and indirectly affects the patient\'s rehabilitation. Adequate family resources can reduce the burden and pressure on families. But there is an absence of systematic family resource indicators for people with schizophrenic disorder in China.
OBJECTIVE: This study aimed to develop a set of family resource indicators for people with schizophrenic disorder in China.
METHODS: Preliminary family resource indicators were generated and refined by literature review and an expert consultation meeting. Two rounds of email-based Delphi survey were carried out to identify family resource indicators.
METHODS: Two rounds of email-based Delphi survey were performed from July to September 2021 in Beijing, China.
METHODS: There were 15 mental health doctors from community health service centres and four psychiatrists from tertiary hospitals, and two primary care researchers from universities in the first and second rounds Delphi survey.
RESULTS: All the 21 experts participated in both rounds of Delphi survey. A total of 46 indicators achieved consensus for inclusion in the final set of indicators after two rounds of Delphi survey. The final set of indicators was grouped into 10 domains: financial support (three indicators), psychological and spiritual support (eight indicators), medical treatment (three indicators), information and education (three indicators), structural support (two indicators), external family resources included social resources (five indicators), cultural resources (two indicators), economic resources (seven indicators), environmental resources (four indicators) and medical resources (nine indicators).
CONCLUSIONS: A set of 46 family resource indicators for people with schizophrenic disorder in community was identified by an iterative Delphi process in Beijing, China. However, the indicators still need to be validated by testing in further studies.