Error monitoring dysfunction across the illness course of schizophrenia.
Ontology highlight
ABSTRACT:
SUBMITTER: Perez VB
PROVIDER: S-EPMC3358508 | biostudies-literature | 2012 May
REPOSITORIES: biostudies-literature
Publications
Error monitoring dysfunction across the illness course of schizophrenia.
Perez Veronica B VB Ford Judith M JM Roach Brian J BJ Woods Scott W SW McGlashan Thomas H TH Srihari Vinod H VH Loewy Rachel L RL Vinogradov Sophia S Mathalon Daniel H DH
Journal of abnormal psychology 20111107 2
Response monitoring abnormalities have been reported in chronic schizophrenia patients, but it is unknown whether they predate the onset of psychosis, are present in early stages of illness, or are late-developing abnormalities associated with illness progression. Response-synchronized event-related potentials (ERP) recorded during a picture-word matching task yielded error-related negativity (ERN), correct-response negativity (CRN), and error positivity (Pe) from 84 schizophrenia patients (SZ), ...[more]
Similar Datasets
Project description:Understanding whether and how the schizophrenia polygenic risk score (SZ PRS) predicts course of illness could improve diagnosis and prognostication in psychotic disorders. We tested whether the SZ PRS predicts symptoms, cognition, illness severity, and diagnostic changes over the 20 years following first admission. The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Patients were assessed six times over 20 years, and 249 provided DNA. Geographically- and demographically-matched never psychotic adults were recruited at year 20, and 205 provided DNA. Symptoms were rated using the Schedule for the Assessment of Positive Symptoms and Schedule for the Assessment of Negative Symptoms. Cognition was evaluated with a comprehensive neuropsychological battery. Illness severity and diagnosis were determined by consensus of study psychiatrists. SZ PRS was significantly higher in first-admission than never psychotic groups. Within the psychosis cohort, the SZ PRS predicted more severe negative symptoms (??=?0.21), greater illness severity (??=?0.28), and worse cognition (??=?-0.35), across the follow-up. The SZ PRS was the strongest predictor of diagnostic shifts from affective to non-affective psychosis over the 20 years (AUC?=?0.62). The SZ PRS predicts persistent differences in cognition and negative symptoms. The SZ PRS also predicts who among those who appear to have a mood disorder with psychosis at first admission will ultimately be diagnosed with a schizophrenia spectrum disorder. These findings show potential for the SZ PRS to become a tool for diagnosis and treatment planning.
| S-EPMC6856168 | biostudies-literature
Project description:Objective:Schizophrenia poses a tremendous health, social, and economic burden upon patients and society, indicating current treatment options remain inadequate. Recent findings from several lines of evidence have pointed to the importance of immune system involvement in not only premorbid neurodevelopmental but also subsequent symptom generation and aging processes of brain change in schizophrenia. In this meta-review, we use the summarized evidence from recent quantitative systematic reviews (SRs) and meta-analyses of several subspecialties to critically evaluate the hypothesis that immune-related processes shape the symptomatic presentation and illness course of schizophrenia, both directly and indirectly through altered neuroplasticity. Methods:We performed a data search in PubMed for English language SRs and meta-analyses from 2010 to 2017. The methodological quality of the SRs was assessed with the AMSTAR instrument. In addition, we review in this paper 11 original publications on translocator protein (TSPO) positron emission tomography (PET) imaging in schizophrenia. Results:We reviewed 26 SRs and meta-analyses. Evidence from clinical observational studies of inflammatory or immunological markers and randomized controlled drug trials of immunomodulatory compounds as add-on in the treatment of schizophrenia suggests psychotic exacerbations are accompanied by immunological changes different from those seen in non-acute states, and that the symptoms of schizophrenia can be modified by compounds such as non-steroidal anti-inflammatory drug and minocycline. Information derived from post-mortem brain tissue analysis and PET neuroimaging studies to evaluate microglial activation have added new perspectives to the available evidence, yet these results are very heterogeneous. Each research domain comes with unique opportunities as well as inherent limitations. A better understanding of the (patho-)physiology of microglial cells and their role in neuroplasticity is key to interpreting the immune-related findings in the context of schizophrenia illness exacerbations and progression. Conclusion:Evidence from clinical studies analyzing patients' blood and cerebrospinal fluid samples, neuroimaging and post-mortem brain tissue suggests that aberrant immune responses may define schizophrenia illness' course through altered neuroplasticity representing abnormal aging processes. Most findings are however prone to bias and confounding, and often non-specific to schizophrenia, and a multidisciplinary translational approach is needed to consolidate these findings and link them to other schizophrenia hypotheses.
| S-EPMC5696326 | biostudies-literature
Project description:Pro/antioxidant imbalance has been reported in schizophrenia (SZ). However, the results of studies are inconsistent and usually do not include other factors that are highly affected by oxidative stress (OS).This cross-sectional study aimed to determine the serum levels of OS markers and their potential connection with schizophrenia. The total sample comprised 147: 98 individuals with SZ -47 first-episode (FS) and 49 chronic patients (CS)-and 49 healthy individuals (HC) as a control group. The examination included clinical variables and serum levels of antioxidants and oxidative damage products. The significant changes were observed in concentrations of all examined markers, without any specific direction of the pro/antioxidant balance shift between SZ and HC. In the regression model adjusted for cofounders, catalase: OR = 0.81 (95%CI: 0.74-0.88); glutathione peroxidase: OR = 1.06 (95%CI: 1.02-1.10); total antioxidant capacity: OR = 0.85 (95%CI: 0.75-0.98); oxidative stress index: OR = 1.25 (95%CI: 1.03-1.52); ferric reducing ability of plasma: OR = 0.79 (95%CI: 0.69-0.89); advanced glycation end products: OR = 1.03 (95%CI: 1.01-1.04); and advanced oxidation protein products (AOPP): OR = 1.05 (95%CI: 1.03-1.07) turned out to be significant predictors of schizophrenia. In the multiple stepwise regression model, pro/antioxidant status and their interaction with the duration of illness-related factors affected schizophrenia symptoms: positive symptoms (FRAPxKYN), negative (DITYR, FRAP, CAT), general (KYN), and over-all psychopathology (KYNxNFK). The results confirm differences in serum levels of oxidative biomarkers between SZ patients and healthy individuals. The pro/antioxidant status could be considered a predictor of schizophrenia and the factor affects patients' symptom severity.
| S-EPMC8636114 | biostudies-literature
Project description:With advanced understanding of the intricate interplay between the immune and central nervous systems in neurological and neuropsychiatric illness, there is renewed interest in the potential contribution of immune dysregulation to the development and progression of schizophrenia. To inform this line of inquiry requires a more nuanced understanding of specific immune changes throughout the course of illness. Here, we utilized a genome-wide sequencing approach to transcriptionally profile circulating monocytes in participants with chronic schizophrenia. These myeloid cells, isolated from whole blood samples, are highly plastic with potentially important disease-modifying functions. Differential gene expression and gene set enrichment analyses, focusing on established monocyte phenotypic signatures, including those related to proinflammatory ("M1-like") and protective or tissue remodeling ("M2-like") functions, were carried out. We demonstrate an overall enrichment of both "M1-like" (interferon-alpha, interferon-gamma, lipopolysaccharide acute) and "M2-like" (endotoxin tolerance, glucocorticoid acute) monocyte signatures in the participants with schizophrenia compared to non-psychiatric controls. There was no enrichment of the "M1-like" chronic stress signature or the "M2-like" interleukin-4 signature. Using the Molecular Signatures Database Hallmark gene sets list, the "interferon response" was most strongly enriched in schizophrenia compared to controls. Additionally, an exploratory subgroup analysis based on illness duration suggests a shift in monocyte phenotype with illness progression. Specifically, the "M1-like" interferon-gamma signature shows decreased enrichment accompanied by increased enrichment of opposing "M2-like" signatures in participants with a medium illness duration shifting to a strong enrichment of interferon response signatures only in participants with a long illness duration. These findings related to circulating immune cell phenotype have potentially important implications for understanding the role of immune dysregulation in schizophrenia and are a critical consideration for future study design and immune-targeting treatment strategies.
| S-EPMC8160367 | biostudies-literature
Project description:Visual integration dysfunction characterizes schizophrenia, but prior studies have not yet established whether the problem arises by the first psychotic episode or worsens with illness duration. To investigate the issue, we compared chronic schizophrenia patients (SZs), first episode psychosis patients (FEs), and well-matched healthy controls on a brief but sensitive psychophysical task in which subjects attempted to locate an integrated shape embedded in noise. Task difficulty depended on the number of noise elements co-presented with the shape. For half of the experiment, the entire display was scaled down in size to produce a high spatial frequency (HSF) condition, which has been shown to worsen patient integration deficits. Catch trials-in which the circular target appeared without noise-were also added so as to confirm that subjects were paying adequate attention. We found that controls integrated contours under noisier conditions than FEs, who, in turn, integrated better than SZs. These differences, which were at times large in magnitude (d = 1.7), clearly emerged only for HSF displays. Catch trial accuracy was above 95% for each group and could not explain the foregoing differences. Prolonged illness duration predicted poorer HSF integration across patients, but age had little effect on controls, indicating that the former factor was driving the effect in patients. Taken together, a brief psychophysical task efficiently demonstrates large visual integration impairments in schizophrenia. The deficit arises by the first psychotic episode, worsens with illness duration, and may serve as a biomarker of illness progression. (PsycINFO Database Record
| S-EPMC4850085 | biostudies-literature
Project description:Current theories of cognitive dysfunction in schizophrenia emphasize an impairment in the ability of individuals suffering from this disorder to monitor their own performance, and adjust their behavior to changing demands. Detecting an error in performance is a critical component of evaluative functions that allow the flexible adjustment of behavior to optimize outcomes. The dorsal anterior cingulate cortex (dACC) has been repeatedly implicated in error-detection and implementation of error-based behavioral adjustments. However, accurate error-detection and subsequent behavioral adjustments are unlikely to rely on a single brain region. Recent research demonstrates that regions in the anterior insula, inferior parietal lobule, anterior prefrontal cortex, thalamus, and cerebellum also show robust error-related activity, and integrate into a functional network. Despite the relevance of examining brain activity related to the processing of error information and supporting behavioral adjustments in terms of a distributed network, the contribution of regions outside the dACC to error processing remains poorly understood. To address this question, we used functional magnetic resonance imaging to examine error-related responses in 37 individuals with schizophrenia and 32 healthy controls in regions identified in the basic science literature as being involved in error processing, and determined whether their activity was related to behavioral adjustments. Our imaging results support previous findings showing that regions outside the dACC are sensitive to error commission, and demonstrated that abnormalities in brain responses to errors among individuals with schizophrenia extend beyond the dACC to almost all of the regions involved in error-related processing in controls. However, error related responses in the dACC were most predictive of behavioral adjustments in both groups. Moreover, the integration of this network of regions differed between groups, with the cerebellar regions and the dACC less connected to the network in individuals with schizophrenia compared to controls. Our findings demonstrate a blunted response to error commission in the dACC that is associated with reduced error-related behavioral adjustments in individuals with schizophrenia. This result supports the hypothesis that a failure to respond appropriately to errors in individuals with schizophrenia is linked to alterations in dACC function leading to a compromise in the implementation of cognitive control. Our findings highlight the importance of examining brain activity related to the processing of error information and supporting error-related behavioral adjustments in terms of a distributed network.
| S-EPMC2997133 | biostudies-literature
Project description:Goal-directed human behavior is enabled by hierarchically-organized neural systems that process executive commands associated with higher brain areas in response to sensory and motor signals from lower brain areas. Psychiatric diseases and psychotic conditions are postulated to involve disturbances in these hierarchical network interactions, but the mechanism for how aberrant disease signals are generated in networks, and a systems-level framework linking disease signals to specific psychiatric symptoms remains undetermined. In this study, we show that neural networks containing schizophrenia-like deficits can spontaneously generate uncompensated error signals with properties that explain psychiatric disease symptoms, including fictive perception, altered sense of self, and unpredictable behavior. To distinguish dysfunction at the behavioral versus network level, we monitored the interactive behavior of a humanoid robot driven by the network. Mild perturbations in network connectivity resulted in the spontaneous appearance of uncompensated prediction errors and altered interactions within the network without external changes in behavior, correlating to the fictive sensations and agency experienced by episodic disease patients. In contrast, more severe deficits resulted in unstable network dynamics resulting in overt changes in behavior similar to those observed in chronic disease patients. These findings demonstrate that prediction error disequilibrium may represent an intrinsic property of schizophrenic brain networks reporting the severity and variability of disease symptoms. Moreover, these results support a systems-level model for psychiatric disease that features the spontaneous generation of maladaptive signals in hierarchical neural networks.
| S-EPMC3364276 | biostudies-literature
Project description:Critical care practitioners must frequently make decisions about their patients' ability to swallow food, liquids, and pills. These decisions can be particularly difficult given the incompletely defined epidemiology, diagnostic criteria, and prognostic features of swallowing disorders in critically ill patients. Furthermore, the consequences of improper decisions-namely, aspiration, malnutrition, hunger, and thirst-can be devastating to patients and their families. This review outlines the problem of swallowing dysfunction in critically ill patients and then addresses the most clinically relevant questions that critical care practitioners face today. First, we review the epidemiology of swallowing dysfunction in critically ill patients. Next, we describe the different diagnostic tests for swallowing dysfunction and describe a general approach to the initial assessment for swallowing disorders. Finally, we explore the existing treatments for swallowing dysfunction. Given the burden of swallowing dysfunction in patients recovering from critical illness, enabling critical care practitioners to manage these disorders, while stimulating new investigation into their pathophysiology, diagnosis, and management, will enhance our care of critically ill patients.
| S-EPMC4251623 | biostudies-other
Project description:Guaranteeing high-quality next-generation sequencing data in a rapidly changing environment is an ongoing challenge. The introduction of the Illumina NextSeq 500 and the depreciation of specific metrics from Illumina's Sequencing Analysis Viewer (SAV; Illumina, San Diego, CA, USA) have made it more difficult to determine directly the baseline error rate of sequencing runs. To improve our ability to measure base quality, we have created an open-source tool to construct the Percent Perfect Reads (PPR) plot, previously provided by the Illumina sequencers. The PPR program is compatible with HiSeq 2000/2500, MiSeq, and NextSeq 500 instruments and provides an alternative to Illumina's quality value (Q) scores for determining run quality. Whereas Q scores are representative of run quality, they are often overestimated and are sourced from different look-up tables for each platform. The PPR's unique capabilities as a cross-instrument comparison device, as a troubleshooting tool, and as a tool for monitoring instrument performance can provide an increase in clarity over SAV metrics that is often crucial for maintaining instrument health. These capabilities are highlighted.
| S-EPMC5026502 | biostudies-literature
Project description:The ability to read passages of information fluently and with comprehension is a basic component of socioeconomic success. Reading ability depends on the integrity of underlying visual and auditory (phonological) systems. This study investigated the integrity of reading ability in schizophrenia relative to the integrity of underlying visual and auditory function.The participants were 45 schizophrenia patients, 19 clinical high-risk patients, and 65 comparison subjects. Reading was assessed using tests sensitive to visual or phonological reading dysfunction. Sensory, neuropsychological, and functional outcome measures were also obtained.Schizophrenia patients displayed reading deficits that were far more severe (effect size >2.0) than would be predicted based on general neurocognitive impairments (effect size 1.0-1.4). The deficits correlated highly with both visual and auditory sensory measures, including impaired mismatch negativity generation (r=0.62, N=51, p=0.0002). Patients with established schizophrenia displayed both visual and phonological impairments, whereas high-risk patients showed isolated visual impairments. More than 70% of schizophrenia patients met criteria for acquired dyslexia, with 50% reading below eighth grade level despite intact premorbid reading ability. Reading deficits also correlated significantly (rp=0.4, N=30, p=0.03) with failure to match parental socioeconomic achievement, over and above contributions of more general cognitive impairment.Patients with schizophrenia display severe deficits in reading ability that represent a potentially remediable cause of impaired socioeconomic function. Such deficits are not presently captured during routine clinical assessment. Deficits most likely develop during the years immediately surrounding illness onset and may contribute to the reduced educational and occupational achievement associated with schizophrenia.
| S-EPMC4501394 | biostudies-literature