Schizophrenia (Heidelberg, Germany)最新文献

Limited negative symptoms treatment effectiveness may result from environmental resource deprivation that is a barrier for performing goal-directed, recreational, and social activities. This study showed that environmental resource deprivation in the home environment was greater for people with schizophrenia (n = 39) than 32 demographically-matched healthy controls (CN). Greater environmental resource reductions for performing goal-directed, recreational, and social activities were associated with greater negative symptoms, even after controlling for income and secondary negative symptom factors (depression, positive symptoms).

Clinical ascertainment and clinical outcome are key features of any large multisite study. In the ProNET and PRESCIENT research networks, the Accelerating Medicines Partnership^® Schizophrenia (AMP^®SCZ) Clinical Ascertainment and Outcome Measures Team aimed to establish a harmonized clinical assessment protocol across these two research networks and to define ascertainment criteria and primary and secondary endpoints. In addition to developing the assessment protocol, the goals of this aspect of the AMP SCZ project were: (1) to implement and monitor clinical training, ascertainment of participants, and clinical assessments; (2) to provide expert clinical input to the Psychosis Risk Evaluation, Data Integration and Computational Technologies: Data Processing, Analysis, and Coordination Center (PREDICT-DPACC) for data collection, quality control, and preparation of data for the analysis of the clinical measures; and (3) to provide ongoing support to the collection, analysis, and reporting of clinical data. This paper describes the (1) protocol clinical endpoints and outcomes, (2) rationale for the selection of the clinical measures, (3) extensive training of clinical staff, (4) preparation of clinical measures for a multisite study which includes several sites where English is not the native language; and (5) the assessment of measure stability over time in the AMP SCZ observational study comparing clinical ratings at baseline and at the 2-month follow up. Watch Dr. Jean Addington discuss her work and this article: https://vimeo.com/1040425281 .

Modern research management, particularly for publicly funded studies, assumes a data governance model in which grantees are considered stewards rather than owners of important data sets. Thus, there is an expectation that collected data are shared as widely as possible with the general research community. This presents problems in complex studies that involve sensitive health information. The latter requires balancing participant privacy with the needs of the research community. Here, we report on the data operation ecosystem crafted for the Accelerating Medicines Partnership® Schizophrenia project, an international observational study of young individuals at clinical high risk for developing a psychotic disorder. We review data capture systems, data dictionaries, organization principles, data flow, security, quality control protocols, data visualization, monitoring, and dissemination through the NIMH Data Archive platform. We focus on the interconnectedness of these steps, where our goal is to design a seamless data flow and an alignment with the FAIR (Findability, Accessibility, Interoperability, and Reusability) principles while balancing local regulatory and ethical considerations. This process-oriented approach leverages automated pipelines for data flow to enhance data quality, speed, and collaboration, underscoring the project's contribution to advancing research practices involving multisite studies of sensitive mental health conditions. An important feature is the data's close-to-real-time quality assessment (QA) and quality control (QC). The focus on close-to-real-time QA/QC makes it possible for a subject to redo a testing session, as well as facilitate course corrections to prevent repeating errors in future data acquisition. Watch Dr. Sylvain Bouix discuss his work and this article: https://vimeo.com/1025555648 .

The Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ) project assesses a large sample of individuals at clinical high-risk for developing psychosis (CHR) and community controls. Subjects are enrolled in 43 sites across 5 continents. The assessments include domains similar to those acquired in previous CHR studies along with novel domains that are collected longitudinally across a period of 2 years. In parallel with the data acquisition, multidisciplinary teams of experts have been working to formulate the data analysis strategy for the AMP SCZ project. Here, we describe the key principles for the data analysis. The primary AMP SCZ analysis aim is to use baseline clinical assessments and multimodal biomarkers to predict clinical endpoints of CHR individuals. These endpoints are defined for the AMP SCZ study as transition to psychosis (i.e., conversion), remission from CHR syndrome, and persistent CHR syndrome (non-conversion/non-remission) obtained at one year and two years after baseline assessment. The secondary aim is to use longitudinal clinical assessments and multimodal biomarkers from all time points to identify clinical trajectories that differentiate subgroups of CHR individuals. The design of the analysis plan is informed by reviewing legacy data and the analytic approaches from similar international CHR studies. In addition, we consider properties of the newly acquired data that are distinct from the available legacy data. Legacy data are used to assist analysis pipeline building, perform benchmark experiments, quantify clinical concepts and to make design decisions meant to overcome the challenges encountered in previous studies. We present the analytic design of the AMP SCZ project, mitigation strategies to address challenges related to the analysis plan, provide rationales for key decisions, and present examples of how the legacy data have been used to support design decisions for the analysis of the multimodal and longitudinal data. Watch Prof. Ofer Pasternak discuss his work and this article: https://vimeo.com/1023394132?share=copy#t=0 .

Neuroimaging with MRI has been a frequent component of studies of individuals at clinical high risk (CHR) for developing psychosis, with goals of understanding potential brain regions and systems impacted in the CHR state and identifying prognostic or predictive biomarkers that can enhance our ability to forecast clinical outcomes. To date, most studies involving MRI in CHR are likely not sufficiently powered to generate robust and generalizable neuroimaging results. Here, we describe the prospective, advanced, and modern neuroimaging protocol that was implemented in a complex multi-site, multi-vendor environment, as part of the large-scale Accelerating Medicines Partnership® Schizophrenia Program (AMP® SCZ), including the rationale for various choices. This protocol includes T1- and T2-weighted structural scans, resting-state fMRI, and diffusion-weighted imaging collected at two time points, approximately 2 months apart. We also present preliminary variance component analyses of several measures, such as signal- and contrast-to-noise ratio (SNR/CNR) and spatial smoothness, to provide quantitative data on the relative percentages of participant, site, and platform (i.e., scanner model) variance. Site-related variance is generally small (typically <10%). For the SNR/CNR measures from the structural and fMRI scans, participant variance is the largest component (as desired; 40-76%). However, for SNR/CNR in the diffusion scans, there is substantial platform-related variance (>55%) due to differences in the diffusion imaging hardware capabilities of the different scanners. Also, spatial smoothness generally has a large platform-related variance due to inherent, difficult to control, differences between vendors in their acquisitions and reconstructions. These results illustrate some of the factors that will need to be considered in analyses of the AMP SCZ neuroimaging data, which will be the largest CHR cohort to date.Watch Dr. Harms discuss this article at https://vimeo.com/1059777228?share=copy#t=0 .

The Positive and Negative Syndrome Scale (PANSS) is widely used to assess schizophrenia symptoms. Initially designed with three subscales, Marder et al.´s 5-factor-Model (M5M) first proposed in 1997 has been frequently used in treatment trials, but it has never been systematically reviewed for its measurement properties. We utilized the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline for systematic reviews and meta-analytical procedures to assess the psychometric properties of the M5M-PANSS. COSMIN comprises several steps: literature search, risk-of-bias assessments, assessing the updated criteria for good measurement properties, feasibility aspects and grading the quality of the evidence. We further assessed the goodness of fit of other PANSS factor models. We included 95 publications. The M5M-PANSS showed good construct validity, but "insufficient" structural validity. Evidence of other COSMIN domains is largely lacking. Among the multiple (73) factor solutions examined with confirmatory methods, several other 5-factor solutions had better model fit. According to COSMIN rules the M5M should not be recommended for use. Other five-factor models such as the one proposed by Wallwork et al.¹ warrant further evaluation. Nevertheless, the factor composition of the M5M and these other models was relatively similar, so previously published results should not be disregarded.

Although MK801-induced NMDA receptor (NMDAR) hypofunction mimics schizophrenia symptoms, the exact factors causing NMDAR inhibition are unknown. Unexpectedly, external stress elicits formaldehyde (FA) generation; FA can induce depression and cognitive impairments by blocking NMDARs. This study explores using FA injection to establish a schizophrenia-like model in mice. Here, we reported that external stress-derived FA induces schizophrenia-like behaviors. Four experimental methods were used to induce schizophrenia-like symptoms in wild-type mice: double electrode stimulation of the ventral tegmental area (VTA), microinjection of FA or tetrahydroisoquinoline (TIQ) into the VTA, and intraperitoneal injection of MK801. Then the metabolic levels of FA and dopamine (DA) in the prefrontal cortex (PFC) and VTA were quantified using ELISA kits. We found that external stress-electrical stimulation via VTA caused schizophrenia-like behaviors, including despairing behavior as measured by the tail suspension test, anhedonia as evaluated by the sucrose preference test, stereotypical behavior as assessed by the marble burying test (MBT), anxiety-like behavior as measured by the open-field test and memory deficit as detected by the Y-maze. These behaviors correlated with increased DA and TIQ levels in the VTA and decreased DA levels in the PFC. High-resolution mass spectrometry (HRMS) and high-performance liquid chromatography (HPLC) confirmed TIQ formation from FA and DA. Furthermore, injecting TIQ into the VTA induced schizophrenia-like symptoms in mice, marked by higher FA and lower DA levels in the PFC than control mice. Strikingly, injecting FA into the VTA as well as administering MK-801 induced schizophrenia-like behaviors associated with reduced DA levels and low activity of tyrosine hydroxylase (TH) and monoamine oxidase (MAO) in the PFC. Hence, microinfusion of FA into the VTA can be used to prepare schizophrenia-like changes mouse model, suggesting that stress-derived FA may act as an endogenous trigger of schizophrenia-like changes.

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating Medicines Partnership® program for Schizophrenia (AMP SCZ initiative). The aim of this paper is to describe the rationale, processes, considerations, and final harmonization of the cognitive battery used in AMP SCZ across the two data collection networks. This battery comprises tests of general intellect and specific cognitive domains. We estimate premorbid intelligence at baseline and measure current intelligence at baseline and 2 years. Eight tests from the Penn Computerized Neurocognitive Battery (PennCNB), which measure verbal learning and memory, sensorimotor ability, attention, emotion recognition, working memory, processing speed, verbal memory, visual memory, and motor speed are administered repeatedly at baseline, and four follow-up timepoints over 2 years.

The hypoactivity of parvalbumin-containing interneurons (PV-interneurons) is a pathogenetic mechanism of schizophrenia according to the glutamatergic theory, and PV-interneurons are necessary for the generation of EEG/MEG gamma-frequencies (30-100 Hz). The present study aims to a literature synthesis on resting-state gamma-frequency changes in patients with schizophrenia vs healthy controls, and to examine the relationship between these changes and severity of symptoms. A protocol was enregistered in PROSPERO and a systematic search was conducted in PubMed, PsycINFO and Cochrane Database of Systematic Reviews, following PRISMA guidelines. An exploratory metanalysis was realized. Out of 1391 records, 43 were included for a qualitative synthesis (N = 2133 [11-185], females 37.4%, age 33.9 ± 9.2). Results on power spectra were heterogeneous: in 12 studies gamma power was increased, involving the whole brain (N = 3), multiple regions (N = 6) or only frontal (N = 1), central (n = 1) and temporal (N = 1) areas; in 3 studies gamma power was reduced, involving multiple areas (N = 2) or the right temporal region (N = 1); one study revealed mixed results and 13 studies showed no differences. The meta-analysis on 4 studies (N = 211) showed non-significant differences between patients and controls and a large heterogeneity. The functional connectivity picture consists of sparse patterns of decreases and/or increases, widespread to multiple regions. Relationships emerged between gamma power and connectivity and severity of psychotic and cognitive symptoms. Theta-gamma coupling was increased in patients, with limited evidence for other changes in phase-amplitude coupling. Resting-state gamma-frequencies alterations in schizophrenia were inconsistent across studies; the heterogeneity of patients and methods could partially explain this outcome.