Aim
We previously reported abnormal P300 and N200 in a visual oddball task, and progressive P300 amplitude reduction at 1‐year follow‐up in patients with first‐episode schizophrenia. P300 reduction ...as well as intact P1/N1 were also observed in clinical high‐risk subjects (CHR), but whether or not these components change over time is unknown. This study evaluates, longitudinally, the visual P300, as well as P1, N1, and N200, in CHR.
Methods
Visual event‐related potentials (ERP) were recorded twice, once at baseline and once at 1‐year follow‐up in CHR (n = 19) and healthy comparison subjects (HC; n = 28). Participants silently counted infrequent target stimuli (‘x’) among standard stimuli (‘y’) presented on the screen while the 64‐channel electroencephalogram was recorded.
Results
No CHR converted to psychosis from baseline to 1‐year follow‐up in this study. Visual P300 amplitude was reduced and the latency was delayed significantly in CHR at both time points compared with HC. Furthermore, CHR subjects who had more positive symptoms showed more amplitude reduction at both time points. P1, N1, and N200 did not differ between groups.
Conclusion
Visual P300 amplitude was found to be reduced in CHR individuals compared with HC. We note that this finding is in subjects who did not convert to psychosis at 1‐year follow‐up. The association between visual P300 amplitude and symptoms suggests that for CHR who often experience clinical symptoms and seek medical care, visual P300 may be an important index that reflects the pathophysiological impairment underlying such clinical states.
Cognitive dysfunction is a hallmark feature of schizophrenia and is evident across all phases of the illness. While prior meta-analyses have elucidated the level and pattern of cognitive deficits in ...the premorbid and post-onset periods of psychosis, no meta-analyses of studies of the putative prodromal period have been published. Our primary aim is to provide a meta-analysis of neurocognitive findings from 14 studies of psychosis risk syndrome (PRS) individuals published through February 2011, and compare the resulting profile with that synthesized by meta-analyses from other periods of the disorder. Meta-analysis of 1215 PRS individuals with a mean age of 19.2 (± 3.3) and 851 healthy control subjects yielded small-to-medium impairments across nine of 10 neurocognitive domains (Cohen's d = -0.26 to -0.67). Seven studies reported on PRS individuals who later developed psychosis (n = 175) and their baseline performance level generally yielded moderate-to-large ESs (d = -0.35 to -0.84). Mild cognitive deficits are reliably and broadly present in PRS individuals, falling at a level that is intermediate between healthy individuals and those diagnosed with schizophrenia, and at a level that is comparable to those at familial ("genetic") risk and with premorbid data. Moreover, baseline neurocognition in PRS individuals who converted to psychosis showed more severe deficits than non-converters in nearly all domains. However, considerable heterogeneity of ESs across studies in many domains underscores variability in phenotypic expression and/or measurement sensitivity, and a critical need for improved reporting of sample characteristics to support moderator variable analyses.
Neurocognition in First-Episode Schizophrenia Mesholam-Gately, Raquelle I; Giuliano, Anthony J; Goff, Kirsten P ...
Neuropsychology,
05/2009, Letnik:
23, Številka:
3
Journal Article
Recenzirano
Compromised neurocognition is a core feature of schizophrenia. Following
Heinrichs and Zakzanis's (1998)
seminal meta-analysis of middle-aged and predominantly chronic schizophrenia samples, the aim ...of this study is to provide a meta-analysis of neurocognitive findings from 47 studies of first-episode (FE) schizophrenia published through October 2007. The meta-analysis uses 43 separate samples of 2,204 FE patients with a mean age of 25.5 and 2,775 largely age- and gender-matched control participants. FE samples demonstrated medium-to-large impairments across 10 neurocognitive domains (mean effect sizes from −0.64 to −1.20). Findings indicate that impairments are reliably and broadly present by the FE, approach or match the degree of deficit shown in well-established illness, and are maximal in immediate verbal memory and processing speed. Larger IQ impairments in the FE compared to the premorbid period, but comparable to later phases of illness suggests deterioration between premorbid and FE phases followed by deficit stability at the group level. Considerable heterogeneity of effect sizes across studies, however, underscores variability in manifestations of the illness and a need for improved reporting of sample characteristics to support moderator variable analyses.
Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical ...thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = -0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = -0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.
Diffusion MRI has been successful in identifying the existence of white matter abnormalities in schizophrenia in vivo. However, the role of these abnormalities in the etiology of schizophrenia is not ...well understood. Accumulating evidence from imaging, histological, genetic, and immunochemical studies support the involvement of axonal degeneration and neuroinflammation--ubiquitous components of neurodegenerative disorders--as the underlying pathologies of these abnormalities. Nevertheless, the current imaging modalities cannot distinguish neuroinflammation from axonal degeneration, and therefore provide little specificity with respect to the pathophysiology progression and whether it is related to a neurodegenerative process. Free-water imaging is a new methodology that is sensitive to water molecules diffusing in the extracellular space. Excessive extracellular volume is a surrogate biomarker for neuroinflammation and can be separated out to reveal abnormalities such as axonal degeneration that affect diffusion characteristics in the tissue. We applied free-water imaging on diffusion MRI data acquired from schizophrenia-diagnosed human subjects with a first psychotic episode. We found a significant increase in the extracellular volume in both white and gray matter. In contrast, significant signs of axonal degeneration were limited to focal areas in the frontal lobe white matter. Our findings demonstrate that neuroinflammation is more prominent than axonal degeneration in the early stage of schizophrenia, revealing a pattern shared by many neurodegenerative disorders, in which prolonged inflammation leads to axonal degeneration. These findings promote anti-inflammatory treatment for early diagnosed schizophrenia patients.
About one in 100 people worldwide are diagnosed with schizophrenia. Many people advocate for a name change for the condition, pointing to the stigma and discrimination associated with the term ...“schizophrenia”, as well as to how the name poorly characterizes features of the illness. The purpose of this project was to collect opinions from a broad, diverse sample of stakeholders about possible name changes for schizophrenia. The project represented a partnership between researchers, clinicians, and those with lived experience with psychosis. The group developed a survey to assess opinions about the need for change in the name schizophrenia as well as potential alternate names. We accumulated 1190 responses from a broad array of community stakeholders, including those with lived experience of mental illness, family members, clinicians, researchers, government officials, and the general public. Findings indicated that the majority of respondents (74.1%) favored a name change for schizophrenia. Most (71.4%) found the name stigmatizing. Of the proposed alternate names, those with the most support included “Altered Perception Syndrome”, “Psychosis Spectrum Syndrome”, and “Neuro-Emotional Integration Disorder”. Survey findings provide strong support for renaming schizophrenia. Most expressed hope that a name change will reduce stigma and discrimination.
Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help ...elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population.
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