Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Schizophrenia patients were known to have oculomotor abnormalities for decades and several studies had found antisaccade impairment to be a biological marker of schizophrenia. In this study, we used functional magnetic resonance imaging (fMRI) to investigate the neural circuits responsible for antisaccade deficits in schizophrenia. Ten normal controls and 10 DSM-IV schizophrenia patients performed antisaccade tasks and control tasks during fMRI. Data were analyzed and task-specific activations were identified using Statistical Parametric Mapping (SPM-2). In normal subjects, antisaccade tasks activated bilateral frontal eye fields, supplementary eye fields, inferior frontal gyrus, superior parietal lobules, inferior parietal lobules, occipital visual cortex, cerebellum, thalamus, and lentiform nuclei (P<0.001). By contrast, schizophrenia patients failed to show activation in bilateral lentiform nucleus, bilateral thalamus, and left inferior frontal gyrus during antisaccade performance. Our findings suggest that schizophrenic antisaccade deficits are associated with dysfunction of fronto-striatal-thalamo-cortical circuits previously demonstrated to be responsible for suppression of the reflexive saccade. Left inferior frontal gyrus, which was known to be responsible for response inhibition on "go/no-go" testing, also plays an important role in schizophrenic antisaccade deficit.
 ...
PMID:Neural correlates of antisaccade deficits in schizophrenia, an fMRI study. 1684 21

The brain is known to be structurally abnormal in schizophrenia, with replicated findings between anatomical deficits and some dysfunctions. These structure-function associations have, however, only very rarely been studied in relatives at risk of schizophrenia. We studied the relationships between structure and schizotypal features (assessed using RISC and SIS) and verbal learning and memory (measured using RAVLT) in relatives at high risk of developing schizophrenia and normal controls. Since these behavioural test scores are strong predictors of schizophrenia in the Edinburgh High Risk Study, we hypothesised that these relationships would differ between those high-risk subjects who will develop schizophrenia from those who will not. We performed multiple regressions of the grey matter segments of the subjects and controls, produced using grey matter optimised, voxel-based morphometry, with their RAVLT, SIS and RISC scores in SPM. Where significant relationships were found, we used SPSS to test for subject group by behavioural score interactions. In those high-risk subjects who became ill, grey matter density (GMD) was significantly correlated with RISC in the left superior temporal gyrus. In subjects who remained well, SIS was significantly correlated with GMD in the right pulvinar. Across the whole HR group, GMD in the right medial dorsal thalamic nucleus was significantly correlated with RAVLT. In those subjects who developed symptoms, RAVLT significantly correlated with GMD in right parahippocampal gyrus whereas in those who became ill, significant correlations existed bilaterally in the pulvinar. These results suggest complex and changing patterns of structural-functional relationships in those subjects at high-risk of schizophrenia.
 ...
PMID:Brain-behaviour relationships in people at high genetic risk of schizophrenia. 1692 2

Altered cerebral energy metabolism and mitochondrial dysfunction in periphery and in brain are implicated in the pathophysiology of schizophrenia. This study investigated whether cerebral glucose metabolism (rCGM) abnormalities are linked to altered mitochondrial complex I activity in the periphery, in schizophrenia. Sixteen schizophrenic patients, 8 with total positive PANSS score >or=20 (high positive schizophrenics; HPS), and 8 with total positive score <or=12 (low positive schizophrenics; LPS), and 8 healthy subjects, were analyzed for their complex I activity in platelets mitochondria and underwent FDG-PET scans at rest. Complex I activity was significantly increased only in HPS and was positively correlated with positive PANSS scores. Images were spatially normalized to an SPM template, their intensities normalized based on average brain activity. Hypermetabolism was observed in the basal ganglia, thalamus, amygdala, and brainstem of both patient groups compared with controls, and in LPS patients extended to parts of cerebellum, left and right cingulate gyrus, parietal and frontal lobes. rCGM in basal ganglia and thalamus significantly and positively correlated with complex I activity in the HPS. In the LPS, a negative correlation was identified in the cerebellum and brainstem. In the control group, however, no areas demonstrated significant positive or negative correlation. These results suggest that the correlation between peripheral complex I activity and rCGM in regions implicated in schizophrenia, could be a pathological factor that is differentially expressed in subgroups of schizophrenic patients.
 ...
PMID:Cerebral glucose utilization and platelet mitochondrial complex I activity in schizophrenia: A FDG-PET study. 1732

Single-photon emission computed tomography (SEPCT) and neuropsychological tests were performed in subjects with Asperger's disorder and schizophrenia with a statistical parametric mapping analysis of 99mECD-SPECT images. The SPM analysis of SPECT images demonstrated reduced regional cerebral blood flows in right parietal lobe and right superior temporal gyrus in Asperger's disorder. On the other hand, schizophrenic individuals showed mild hypoperfusions in bilateral frontal lobes. These abnormalities on SEPCT images in Asperser's disorder could be related to the cognitive dysfunction observed in the spatial working memory task and the impairment of gaze processing. The SEPCT study could be helpful to discriminate Asperser's disorder from schizophrenia.
 ...
PMID:[Regional cerebral blood flow changes of right parietal lobe and superior temporal gyrus in Asperger's disorder in comparison with the patients with schizophrenia]. 1739 Jul 11

Verbal fluency deficits in schizophrenia are difficult to interpret because the tasks are multi-factorial and groups differ in total words generated. We manipulated retrieval and switching demands by requiring alternation between over-learned sequences in which retrieval is relatively automatic (OS) and semantic categories requiring increased retrieval effort (SC). Controlled processing was also manipulated by including switching and non-switching conditions, and formal thought disorder (FTD) was assessed with the communication disorders index (CDI). The OS/SC semantic fluency paradigm was administered during fMRI to 13 patients with schizophrenia and 14 matched controls. Images were acquired on a 3 Tesla Siemens scanner using compressed image acquisition to allow for cued overt word production. Subjects alternated between OS, SC, OS-switch, SC-switch, and baseline blocks. Images were pre-processed in SPM-2, and a two-stage random effects analysis tested within and between group contrasts. There were no group performance differences. fMRI analysis did not reveal any group differences during the OS non-switching condition. Both groups produced expected activation in bilateral prefrontal and inferior parietal regions. However, during the SC condition patients had greater activation than controls in left prefrontal, right anterior cingulate, right superior temporal, bilateral thalamus, and left parietal regions. There was also evidence of patient over-activation in prefrontal, superior temporal, superior parietal, and visual association areas when a switching component was added. FTD was negatively correlated with BOLD response in the right anterior cingulate, cuneus and superior frontal gyrus during increased retrieval demand, and positively correlated with fMRI activation in the left lingual gyrus, right fusiform gyrus and left superior parietal lobule during increased switching demand. These results indicate that patients are able to successfully perform effortful semantic fluency tasks during non-speeded conditions. When retrieval is relatively automatic there does not appear to be an effect of schizophrenia on fMRI response. However, when retrieval and controlled processing demands increase, patients have greater activation than controls despite unimpaired task performance. This inefficient BOLD response may explain why patients are slower and less accurate on standard self-paced fluency tasks.
 ...
PMID:Effect of retrieval effort and switching demand on fMRI activation during semantic word generation in schizophrenia. 1815 80

Deficit schizophrenia (DS) represents a promising putative clinical subtype of schizophrenia and is characterized by the presence of primary and enduring negative symptoms. Previous studies have often reported a reduced amount of gray matter within prefrontal and temporal cortices in schizophrenia subjects with prevailing negative symptoms; however, the evidence concerning brain structural abnormalities in patients with DS remains controversial. The aim of the present study was to investigate whether patients with DS differed from those with nondeficit schizophrenia (NDS) with respect to the volume of the dorsolateral prefrontal cortex (DLPFC) and hippocampus, two brain areas considered as key regions in the pathogenesis of schizophrenia. In the present study a 3D-T1w MR imaging procedure and an extensive clinical assessment was carried out in 18 patients with schizophrenia, (10 DS and 8 NDS). 3D MPRAGE images were preprocessed with SPM software and two regions of interest (hippocampus and DLPFC) were manually traced to obtain their gray matter volumes. We found a significant reduction of DLPFC in the entire schizophrenia group, with respect to healthy subjects. Although the subgroup of patients with DS had a more severe clinical picture and more impaired social functioning, the DLPFC volume reduction was greater in NDS than in DS patients. In conclusion, according to our structural neuroimaging findings, DS patients, although characterized by a more severe clinical picture and a worse outcome, show less neurobiological abnormalities.
 ...
PMID:Dorsolateral prefrontal cortex volume in patients with deficit or nondeficit schizophrenia. 2234 77

Progressive disability in schizophrenia has been considered to be associated with onset-age. The objective of this study was to evaluate age onset-related degeneration in rCBF in patients with schizophrenia. We evaluated characteristic changes in brain perfusion by age, gender, medication and clinical symptoms in medicated patients with early-onset (EOS: developed at younger than 40 years old: n = 44) and late-onset (LOS: developed at older than 40 years old: n = 19) schizophrenia and control subjects matched for age and gender (n = 37) using statistical parametric mapping (SPM8) applied to 99mTc-ECD SPECT. We performed SPECT with 99mTc-ECD on the brains of subjects. A voxel-by-voxel group analysis was performed using SPM 8 and ANOVA. rCBF in EOS was found to be reduced in the precentral and inferior frontal gyri; on the other hand, rCBF was reduced in the bilateral postcentral gyrus in LOS. This study revealed a significant difference in brain perfusion between EOS and LOS. The present study might suggest that the characteristic changes in rCBF are related to onset-age in schizophrenia.
 ...
PMID:Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-ECD. 2607 59

The neuronal underpinnings of cortical folding alterations in schizophrenia remain unclear. Theories on the physiological development of cortical folds stress the importance of white matter fibers for this process and disturbances of fiber tracts might be relevant for cortical folding alterations in schizophrenia. Nine-teen patients with schizophrenia and 19 healthy subjects underwent T1-weighted MRI and DTI. Cortical folding was computed using a surface based approach. DTI was analyzed using FSL and SPM 5. Radial diffusivity and cortical folding were correlated covering the entire cortex in schizophrenia. Significantly increased radial diffusivity of the superior longitudinal fasciculus (SLF) in the left superior temporal region was negatively correlated with cortical folding of the left dorsolateral prefrontal cortex (DLPFC) in patients, i.e. higher radial diffusivity, as an indicator for disturbed white matter fiber myelination, was associated with lower cortical folding of the left DLPFC. Patients with pronounced alterations of the SLF showed significantly reduced cortical folding in the left DLPFC. Our study provides novel evidence for a linkage between prefrontal cortical folding alterations and deficits in connecting white matter fiber tracts in schizophrenia and supports the notion that the integrity of white matter tracts is crucial for intact morphogenesis of the cortical folds.
 ...
PMID:Increased white matter radial diffusivity is associated with prefrontal cortical folding deficits in schizophrenia. 2817 81

A relatively large number of studies have investigated the power of structural magnetic resonance imaging (sMRI) data to discriminate patients with schizophrenia from healthy controls. However, very few of them have also included patients with bipolar disorder, allowing the clinically relevant discrimination between both psychotic diagnostics. To assess the efficacy of sMRI data for diagnostic prediction in psychosis we objectively evaluated the discriminative power of a wide range of commonly used machine learning algorithms (ridge, lasso, elastic net and L0 norm regularized logistic regressions, a support vector classifier, regularized discriminant analysis, random forests and a Gaussian process classifier) on main sMRI features including grey and white matter voxel-based morphometry (VBM), vertex-based cortical thickness and volume, region of interest volumetric measures and wavelet-based morphometry (WBM) maps. All possible combinations of algorithms and data features were considered in pairwise classifications of matched samples of healthy controls (N = 127), patients with schizophrenia (N = 128) and patients with bipolar disorder (N = 128). Results show that the selection of feature type is important, with grey matter VBM (without data reduction) delivering the best diagnostic prediction rates (averaging over classifiers: schizophrenia vs. healthy 75%, bipolar disorder vs. healthy 63% and schizophrenia vs. bipolar disorder 62%) whereas algorithms usually yielded very similar results. Indeed, those grey matter VBM accuracy rates were not even improved by combining all feature types in a single prediction model. Further multi-class classifications considering the three groups simultaneously made evident a lack of predictive power for the bipolar group, probably due to its intermediate anatomical features, located between those observed in healthy controls and those found in patients with schizophrenia. Finally, we provide MRIPredict (https://www.nitrc.org/projects/mripredict/), a free tool for SPM, FSL and R, to easily carry out voxelwise predictions based on VBM images.
 ...
PMID:Evaluation of machine learning algorithms and structural features for optimal MRI-based diagnostic prediction in psychosis. 2842 17

Schizophrenia as a single liability model was confronted to the multiple psychotic phenotypes model proposed by the Wernicke-Kleist-Leonhard school, focusing on two: periodic catatonia (PC) and cataphasia (C). Both are stable and heritable psychotic phenotypes with no crossed liability and are coming with the buildup of specific residual symptoms: impairment of psychomotricity for PC and a specific disorganization of thought and language in C. Regional cerebral blood flow (rCBF) was used as a biomarker. We attempted to refute the single phenotype model by looking at relevant and specific rCBF anomalies for PC and C, that would exceed anomalies in common relative to controls (CTR), i.e. looking for a double dissociation. Twenty subjects with PC, 9 subjects with C and 27 matched controls had two MRI QUIPSS-II arterial spin labeling sequences converted in rCBF. One SPM analysis was performed for each rCBF measurement and the results were given as the conjunction of both analysis. There was a clear double dissociation of rCBF correlates between PC and C, both being meaningful relative to their residual symptomatology. In PC: rCBF was increased in the left motor and premotor areas. In C: rCBF was decreased bilaterally in the temporo-parietal junctions. Conversely, in both (schizophrenia): rCBF was increased in the left striatum which is known to be an anti-psychotics' effect. This evidence refuts the single schizophrenia model and suggests better natural foundations for PC and C phenotypes. This pleads for further research on them and further research on naturally founded psychotic phenotypes.
 ...
PMID:A double dissociation between two psychotic phenotypes: Periodic catatonia and cataphasia. 2955 72


<< Previous 1 2 3 Next >>