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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current study provides a complete magnetic resonance imaging (MRI) analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical MRI data sets, obtained at 3 T, from 3 different subject groups: 25 SZ patients, 29 first-degree relatives, and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition toward hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.
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PMID:Association between psychotic symptoms and cortical thickness reduction across the schizophrenia spectrum. 2229 Oct 30

ZIC2 is a causal gene for holoprosencephaly and encodes a zinc-finger-type transcriptional regulator. We characterized Zic2(kd/+) mice with a moderate (40%) reduction in Zic2 expression. Zic2(kd/+) mice showed increased locomotor activity in novel environments, cognitive and sensorimotor gating dysfunctions, and social behavioral abnormalities. Zic2(kd/+) brain involved enlargement of the lateral ventricle, thinning of the cerebral cortex and corpus callosum, and decreased number of cholinergic neurons in the basal forebrain. Because these features are reminiscent of schizophrenia, we examined ZIC2 variant-carrying allele frequencies in schizophrenia patients and in controls in the Japanese population. Among three novel missense mutations in ZIC2, R409P was only found in schizophrenia patients, and was located in a strongly conserved position of the zinc finger domain. Mouse Zic2 with the corresponding mutation showed lowered transcription-activating capacity and had impaired target DNA-binding and co-factor-binding capacities. These results warrant further study of ZIC2 in the pathogenesis of schizophrenia.
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PMID:Zic2 hypomorphic mutant mice as a schizophrenia model and ZIC2 mutations identified in schizophrenia patients. 2235 35

Inferior parietal lobule (IPL) forms an integral part of a critical frontoparietal network, which has been implicated in various clinical symptoms and cognitive deficits seen in schizophrenia. Despite its functional relevance, the relatively few studies that have investigated the structural changes in the IPL report inconsistent findings concerning the nature and localization of these changes. We employed a blinded, automated labelling procedure to measure cortical thickness, surface area and the degree of cortical folding of the two distinct subregions of the IPL (Angular Gyrus and Supramarginal Gyrus) in 57 patients with schizophrenia and 41 controls using high-resolution magnetic resonance imaging. Within the IPL, we observed more pronounced morphological changes in supramarginal gyrus compared to angular gyrus in schizophrenia. While supramarginal gyrus in patients showed reduced gyrification, contracted surface area and thinning, the morphometric changes in angular gyrus were largely confined to a reduction in surface area. Significant hemispheric asymmetry was observed in the gyrification of the supramarginal gyrus. Our findings suggest that in addition to abnormalities in the neurodevelopmental processes that contribute to regional surface area and cortical thickness, a specific defect in cortical folding, especially affecting the left hemisphere, is likely to occur in schizophrenia.
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PMID:Dissociable morphometric differences of the inferior parietal lobule in schizophrenia. 2245 43

Medial temporal lobe (MTL) structures play a central role in episodic memory. Prior studies suggest that individuals with schizophrenia have deficits in episodic memory as well as structural abnormalities of the medial temporal lobe (MTL). While correlations have been reported between MTL volume loss and episodic memory deficits in such individuals, it is not clear whether such correlations reflect the influence of the disease state or of underlying genetic influences that might contribute to risk. We used high resolution magnetic resonance imaging and probabilistic algorithms for image analysis to determine whether MTL structure, episodic memory performance and the relationship between the two differed among groups of 47 healthy control subjects, 50 control siblings, 39 schizophrenia subjects, and 33 siblings of schizophrenia subjects. High-dimensional large deformation brain mapping was used to obtain volume measures of the hippocampus. Cortical distance mapping was used to obtain volume and thickness measures of the parahippocampal gyrus (PHG) and its substructures: the entorhinal cortex (ERC), the perirhinal cortex (PRC), and the parahippocampal cortex (PHC). Neuropsychological data was used to establish an episodic memory domain score for each subject. Both schizophrenia subjects and their siblings displayed abnormalities in episodic memory performance. Siblings of individuals with schizophrenia, and to a lesser extent, individuals with schizophrenia themselves, displayed abnormalities in measures of MTL structure (volume loss or cortical thinning) as compared to control groups. Further, we observed correlations between structural measures and memory performance in both schizophrenia subjects and their siblings, but not in their respective control groups. These findings suggest that disease-specific genetic factors present in both patients and their relatives may be responsible for correlated abnormalities of MTL structure and memory impairment. The observed attenuated effect of such factors on MTL structure in individuals with schizophrenia may be due to non-genetic influences related to the development and progression of the disease on global brain structure and cognitive processing.
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PMID:Medial temporal lobe structure and cognition in individuals with schizophrenia and in their non-psychotic siblings. 2254 43

Decreased cortical thickness and reduced activity as measured by fMRI in the grey matter of the subgenual cingulate cortex have been reported in schizophrenia and bipolar disorder, and cortical grey matter loss has been reliably reported in the frontal and temporal lobes in schizophrenia. The aim of this study was to examine the thickness of each of the six cortical layers in the subgenual cingulate cortex, five frontal lobe and four temporal lobe gyri. We examined two separate cohorts. Cohort 1 examines the subgenual cingulate cortex (SCC) in schizophrenia (n = 10), bipolar disorder (n = 15) and major depressive disorder (n = 20) against control subjects (n = 19). Cohort two examines frontal and temporal gyri in schizophrenia (n = 16), major depressive disorder (n = 6) against matched controls (n = 32). The cohorts were selected with identical clinical criteria, but underwent different tissue processing to contrast the effect of chemical treatment on tissue shrinkage. Measurements of layer I-VI thickness were taken from cresyl-violet- and haematoxylin-stained sections in cohort one and from cresyl-violet- and H&E-stained sections in cohort two. SCC cortical thickness decreased in male subjects with bipolar disorder (p = 0.048), and male schizophrenia cases showed a specific decrease in the absolute thickness of layer V (p = 0.003). Compared to controls, the relative thickness of layer V in the crown of the SCC decreased in schizophrenia (p < 0.001). A significant decrease in total cortical thickness was observed across the frontal lobe in schizophrenia (p < 0.0001), with specific pyramidal layer thinning in layers III (p = 0.0001) and V (p = 0.005). There was no effect of lateralization. No changes were noted in temporal lobe cortical thickness. This study demonstrates diminished pyramidal layer thickness resulting in decreased frontal lobe thickness in schizophrenia.
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PMID:Changes in cortical thickness in the frontal lobes in schizophrenia are a result of thinning of pyramidal cell layers. 2261 45

Cortical abnormalities are considered a neurobiological characteristic of schizophrenia. However, the pattern of such deficits as they progress over the illness remains poorly understood. The goal of this project was to assess the progression of cortical thinning in frontal and temporal cortical regions in schizophrenia, and determine whether relationships exist between them and neuropsychological and clinical symptom profiles. As part of a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy participants (n=20) group-matched for age, gender, and recent-alcohol use, were selected. Using MRI, estimates of gray matter thickness were derived from primary anatomical gyri of the frontal and temporal lobes using surface-based algorithms. These values were entered into repeated-measures analysis of variance models to determine group status and time effects. Change values in cortical regions were correlated with changes in neuropsychological functioning and clinical symptomatology. Results revealed exaggerated cortical thinning of the middle frontal, superior temporal, and middle temporal gyri in schizophrenia participants. These thickness changes strongly influenced volumetric reductions, but were not related to shrinking surface area. Neuropsychological and clinical symptom profiles were stable in the schizophrenia participants despite these neuroanatomic changes. Overall it appears that ongoing abnormalities in the cerebral cortex continue after initial onset of schizophrenia, particularly the lateral aspects of frontal and temporal regions, and do not relate to neuropsychological or clinical measures over time. Maintenance of neuropsychological performance and clinical stability in the face of changing neuroanatomical structure suggests the involvement of alternative compensatory mechanisms.
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PMID:Longitudinal progression of frontal and temporal lobe changes in schizophrenia. 2264 83

Prenatal exposure of the brain to environmental insult causes different neurological symptoms and behavioral outcomes depending on the time of exposure. To examine the cellular bases for these differences, we exposed rhesus macaque fetuses to x-rays during early gestation (embryonic day [E]30-E42), i.e., before the onset of corticogenesis, or in midgestation (E70-E81), when superficial cortical layers are generated. Animals were delivered at term (~E165), and the size and cellular composition of prefrontal association cortex (area 46) examined in adults using magnetic resonance imaging (MRI) and stereologic analysis. Both early and midgestational radiation exposure diminished the surface area and volume of area 46. However, early exposure spared cortical thickness and did not alter laminar composition, and due to higher cell density, neuron number was within the normal range. In contrast, exposure to x-rays at midgestation reduced cortical thickness, mainly due to elimination of neurons destined for the superficial layers. A cell-sparse gap, observed within layer III, was not filled by the later-generated neurons destined for layer II, indicating that there is no subsequent replacement of the lost neurons. The distinct areal and laminar pathology consequent to temporally segregated irradiation is consistent with basic postulates of the radial unit hypothesis of cortical development. In addition, we show that an environmental disturbance inflicted in early gestation can induce subtle cytoarchitectonic alterations without loss of neurons, such as those observed in schizophrenia, whereas midgestational exposure causes selective elimination of neurons and cortical thinning as observed in some forms of mental retardation and fetal alcohol syndrome.
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PMID:Distinct abnormalities of the primate prefrontal cortex caused by ionizing radiation in early or midgestation. 2291 97

The dysmyelinating mouse mutant quaking (qk) is thought to be a model of schizophrenia based on diminution of CNS myelin (Andreone et al., 2007) and downregulation of the Qk gene (Haroutunian et al., 2006) in the brains of schizophrenic patients. The purpose of this study was to identify specific structural defects in the qk mouse CNS that could compromise physiologic function and that in humans might account for some of the cognitive defects characteristic of schizophrenia. Ultrastructural analysis of qk mouse CNS myelinated fibers shows abnormalities in nodal, internodal, and paranodal regions, including marked variation in myelin thickness among neighboring fibers, spotty disruption of paranodal junctions, abnormal distribution of nodal and paranodal ion channel complexes, generalized thinning and incompactness of myelin, and on many axonal profiles complete absence of myelin. These structural defects are likely to cause abnormalities in conduction velocity, synchrony of activation, temporal ordering of signals, and other physiological parameters. We conclude that the structural abnormalities described are likely to be responsible for significant functional impairment both in the qk mouse CNS and in the human CNS with comparable myelin pathology.
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PMID:Structural bases for central nervous system malfunction in the quaking mouse: dysmyelination in a potential model of schizophrenia. 2322 12

ZNF804A SNP rs1344706 confers genome-wide risk for schizophrenia and bipolar disorder. Both disorders affect cortical thickness. To determine if single nucleotide polymorphisms (SNPs) across ZNF804A are associated with cortical thinning, we investigated 63 SNPs (including rs1344706) in 365 psychosis patients and healthy controls. Results show no significant associations.
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PMID:ZNF804A and cortical thickness in schizophrenia and bipolar disorder. 2356 77

Gyrification of the human cerebral cortex starts in the foetus and progresses in early infancy; the pattern of folding in later life provides a lead to early developmental aberration. By studying gyrification at illness onset in adolescence we hoped to clarify the pathophysiology of schizophrenia. Here we find 1) an area of hypergyria includes Broca's area and extends into the Sylvian fissure to encroach on the anterior insula in the left hemisphere, and 2) an area of hypogyria in the superior temporal lobe approximates to Wernicke's area but is located in the right hemisphere and encroaches on the posterior insula. In Broca's/anterior insula area, right lateralization was present in healthy controls but patients were left lateralized: at two year follow-up gyrification had decreased in patients while it increased in controls, and the reduction predicted impaired category fluency. Progressive change was unaccompanied by cortical thinning (investigated only in the brain regions showing baseline changes in gyrification) indicating that the disease process affecting these brain regions (insula, inferior frontal and superior temporal) is not primarily degenerative. A deviation in the lateralized development of peri-Sylvian areas for language production and comprehension appears critical to the pathophysiology of schizophrenia and may point to its species-specific origin.
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PMID:Gyrification of Broca's region is anomalously lateralized at onset of schizophrenia in adolescence and regresses at 2 year follow-up. 2360 98


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