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

Brains from patients with schizophrenia have been reported to contain deficient and dysplastic forebrain neurons containing nitric oxide synthase (NOS). As part of a study of NOS in schizophrenia, we decided to investigate the cerebellum, which has particularly high levels of NOS. We used an autoradiographic method to measure the density and distribution of NOS. Sections of frozen cerebellum removed at autopsy were labelled with the selective NOS inhibitor [3H]L-NG-nitro-arginine. NOS levels were visualized in sagittal sections of vermis from 16 control subjects and 21 schizophrenia patients, and measurements were taken from the three groups of developmentally-distinct lobules I-V, VI-VII and VIII-X. The highest NOS density was in the Purkinje/molecular layer of cerebellar cortex, although there was some NOS in the granule cell layer. There were no differences in Purkinje/molecular or granule cell layer NOS levels between the two groups of subjects. The mild structural faults in cerebellar vermis observed in some patients with schizophrenia probably do not involve reductions in NOS-containing cells.
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PMID:Application of [3H]L-N(G)-nitro-arginine labelling to measure cerebellar nitric oxide synthase in patients with schizophrenia. 878 28

Although H. Rorschach considered the Rorschach test as a perceptual experiment, little research has been done on the experiment. Moreover, the Rorschach signs of perceptual impairment in schizophrenia, which he indicated and many scholars have supported, have never been examined by the perceptual experiments. The purpose of this study is to make clear the relationship between the Rorschach response and the perceptual process in schizophrenia by investigating cognitive activities using eye-mark recorder. Four Rorschach cards were selected, achromatic cards I and V, and chromatic cards II and VIII. Thirty chronic schizophrenic inpatients (who met DSM-III-R for "Residual Type", and whose negative symptoms were evaluated according to SANS) and 20 normals were all administered the Rorschach test in the used manner but they wore an eye-mark recorder. Their eye movements during reporting the initial response to each card were recorded on the VTR connected with the eye-mark recorder. On the response of each card, five eye movement items (1.total response time; 2.number of eye-fixation movements/sec.; 3.mean eye-fixation time; 4.mean eye-fixation tracking length, and 5.eye-fixation frequency on each detail area) were measured and analyzed. By their initial response, subjects were divided into 3 response groups: Popular response group, non-Popular response group and Rejection group. On the achromatic cards I and V, cognitive activities during delivering Popular response in schizophrenia were examined in comparing with those of normals. On the chromatic cards II and VIII, after the eye movements of Popular response group in schizophrenia were compared with those of Normals, scanning activities of the non-Popular group, the Rejection group and the Popular group were investigated in comparing with each other among schizophrenics. On the achromatic cards with the most solid blots; Cards I and V, the schizophrenics could easily give a Popular response the same as normals. However, the visual scanning activity of schizophrenics was limited on a small detail area and inactive compared with normals. The results show the discrepancy between the response and the cognitive activity. On the achromatic cards, this suggests that the Rorschach response process in schizophrenia is different from those of normal's, even if the responses of schizophrenia is the same as those of normals. On the chromatic cards with the most broken blots; Cards II and VIII, most of schizophrenics failed to give any response, hardly gave a Popular response but a non Popular response. Among schizophrenics, the few Popular groups indicated a limited pattern with poor scanning on the blot. Besides in SANS, their negative symptoms showed high attentional impairment. Although the non-Popular group gave many color responses, they avoided looking at the color areas, As for the Rejection group, although eye-fixation shifted and searched all over the blots, the subjects failed to give any response. Particularly on Card II, some of their visual focal points scattered on the white space areas out of the blot. This implies the failure of perception focusing on the appropriate blots as the relative stimulus. This implies the impairment of selective attention in schizophrenia. These results suggest that it didn't reveal in the usual manner of Rorschach test until the observation with eye-mark recorder made it possible to show us the response process in schizophrenia.
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PMID:[Rorschach response process in schizophrenia]. 881 Aug 61

Nicotinic acetylcholine receptors (nAChRs) are membrane-bound, pentameric ligand-gated ion channels associated with a variety of human disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, and pain. Most known nAChRs contain an unusual eight-membered disulfide-containing cysteinyl-cysteine ring, ox-[Cys-Cys], as does the soluble acetylcholine binding protein (AChBP) found in the snail Lymnaea stagnalis. The cysteinyl-cysteine ring is located in a region implicated in ligand binding, and conformational changes involving this ring may be important for modulation of nAChR function. We have studied the preferred conformations of Ac-ox-[Cys-Cys]-NH2 by NMR in water and computationally by Monte Carlo simulations using the OPLS-AA force field and GB/SA water model. ox-[Cys-Cys] adopts four distinct low-energy conformers at slightly above 0 degrees C in water. Two populations are dependent on the peptide omega2 dihedral angle, with the trans amide favored over the cis amide by a ratio of ca. 60:40. Two ox-[Cys-Cys] conformers with a cis amide bond (C+ and C-) differ from each other primarily by variation of the chi3 dihedral angle, which defines the orientation of the helicity about the S-S bond (+/- 90 degrees ). Two trans amide conformers have the same S-S helicity (chi3 approximately -90 degrees ), but are distinguished by a backbone rotation about phi2 and psi1 (T- and T'-). The ratio of T-/T'-/C+/C- is 47:15:29:9. The orientation of the pendant moieties from the eight-membered ring is more compact for the major trans conformer (T-) than for the extended conformations adopted by T'-, C+, and C-. These conformational preferences are also observed in tetrapeptide and undecapeptide fragments of the human alpha7 subtype of the nAChR that contains the ox-[Cys-Cys] unit. Conformer T- is nearly identical to the conformation seen in the X-ray structure of ox-[Cys(187)-Cys(188)] found in the unliganded AChBP, and is a Type VIII beta-turn.
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PMID:Conformational analysis of the eight-membered ring of the oxidized cysteinyl-cysteine unit implicated in nicotinic acetylcholine receptor ligand recognition. 1174 32

In order to understand relationships between scanning behaviors, characteristics of visual stimuli and the clinical symptoms in schizophrenia, eye movements of 37 schizophrenic patients and 36 controls were recorded using an eye-mark recorder during a free-response period in a Rorschach test. Four cards (I, II, V and VIII) were used. Data were analyzed during 15 s from the presentation of each card. For all cards, the number of eye fixations and the number of eye fixation areas were fewer, and total scanning length and mean scanning length were shorter for schizophrenic patients than for controls. For card II, in the non-popular response group, eye fixation frequency upon area 5 + 6 (red) was higher for schizophrenic patients. For card VIII, in the popular response group, eye fixation frequency upon area 5 + 6 (pink) was lower for schizophrenic patients. For cards II and VIII, the number of eye fixations was inversely correlated with negative symptoms. For card II, total scanning length tended to be inversely correlated with negative symptoms, and mean eye fixation time was correlated with negative symptoms. The number of eye fixation areas was inversely correlated with positive symptoms. For card VIII, eye fixation frequency in a stimulative area tended to be correlated with positive symptoms. Scanning behaviors in schizophrenic patients are affected by characteristics of visual stimuli, and partially by clinical symptoms.
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PMID:Eye movements during the Rorschach test in schizophrenia. 1210 59

Henry VI, King of England, at age 19 founded Eton College and King's College, Cambridge. At 31 he had a sudden, dramatic mental illness in which he was mute and unresponsive. Before, he had been paranoid, grandiose, and indecisive. After, he was apathetic with deterioration of ability, drive, interest and self-care, and hallucinations and religious delusions. This illness, which is consistent with a diagnosis of schizophrenia, robbed Henry of his personality, his crown, his wife, his only son, and his life. It led to three decades of brutal fighting for the crown (the 'Wars of the Roses') that resulted in a new dynasty with a dramatic impact on the country: the Tudors, Henry VIII, and Elizabeth I and their descendants. Henry's story illustrates how schizophrenia can devastate individuals and families and change the course of history and yet it raises questions about how achievement and illness are related.
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PMID:Did schizophrenia change the course of English history? The mental illness of Henry VI. 1220 81

An association between cerebellar abnormalities and different manifestations of schizophrenia is increasingly hypothesized, either at the motor (anterior vermis), affective/psychotic (posterior vermis), or cognitive (cerebellar hemispheres) level. However, morphometric and volumetric cerebellar measurements have yielded highly divergent results. The main goal of this study was to use magnetic resonance imaging (MRI) to separately estimate the volumes of the entire vermis, the cerebellar hemispheres and three midsaggital vermian areas among 38 men with schizophrenia and 26 healthy men. Compared with the control group, persons with schizophrenia had significantly smaller volumes of the whole vermis, but not of the cerebellar hemispheres, a difference that approached significance when only the patients without a comorbid diagnosis of alcohol abuse/dependence were considered. Significant anomalies of the posterior vermian areas (lobules VI and VII) were detected in both subgroups of patients, while abnormalities of the anterior vermis (lobules I-V) were observed only among patients with a dual diagnosis of alcoholism. No difference emerged between the groups at the inferior vermian level (lobules VIII-X). Overall, these findings corroborate the hypothesized association between schizophrenia and specific posterior vermian anomalies, which might not necessarily be the consequence of alcohol abuse. However, the suggestion that schizophrenia is related to abnormal volumes of the lateral cerebellum is not supported.
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PMID:MRI volumetry of the vermis and the cerebellar hemispheres in men with schizophrenia. 1531 18

Measures assessing resting-state brain activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) can reveal cognitive disorders at an early stage. Analysis of regional homogeneity (ReHo) measures the local synchronization of spontaneous fMRI signals and has been successfully utilized in detecting alterations in subjects with attention-deficit hyperactivity disorder (ADHD), depression, schizophrenia, Parkinson's disease and Alzheimer's dementia. Resting-state brain activity was investigated in 28 adolescents with autism spectrum disorders (ASD) and 27 typically developing controls being imaged with BOLD fMRI and analyzed with the ReHo method. The hypothesis was that ReHo of resting-state brain activity would be different between ASD subjects and controls in brain areas previously shown to display functional alterations in stimulus or task based fMRI studies. Compared with the controls, the subjects with ASD had significantly decreased ReHo in right superior temporal sulcus region, right inferior and middle frontal gyri, bilateral cerebellar crus I, right insula and right postcentral gyrus. Significantly increased ReHo was discovered in right thalamus, left inferior frontal and anterior subcallosal gyrus and bilateral cerebellar lobule VIII. We conclude that subjects with ASD have right dominant ReHo alterations of resting-state brain activity, i.e., areas known to exhibit abnormal stimulus or task related functionality. Our results demonstrate that there is potential in utilizing the ReHo method in fMRI analyses of ASD.
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PMID:Alterations in regional homogeneity of resting-state brain activity in autism spectrum disorders. 2005 46

Schizophrenia is one of the most severe psychiatric disorders. Increasing evidence implicates that neurodegeneration is a component of schizophrenia pathology and some atypical antipsychotics are neuroprotective and successful in slowing the progressive morphological brain changes. As an antipsychotic agent, clozapine has superior and unique effects, but the intracellular signaling pathways that mediate clozapine action remain to be elucidated. The phosphatidylinositol-3-kinase/protein kinase B/Forkhead box O3 (PI3K/Akt/FoxO3a) pathway is crucial for neuronal survival. However, little information is available regarding this pathway with clozapine. In the present study, we investigated the protective effect of clozapine on the PC12 cells against corticosterone toxicity. Our results showed that corticosterone decreases the phosphorylation of Akt and FoxO3a, leading to the nuclear localization of FoxO3a and the apoptosis of PC12 cells, while clozapine concentration dependently protected PC12 cells against corticosterone insult. Pathway inhibitors studies displayed that the protective effect of clozapine was reversed by LY294002 and wortmannin, two PI3K inhibitors, or Akt inhibitor VIII although several other inhibitors had no effect. The shRNA knockdown results displayed that downregulated Akt1 or FoxO3a attenuated the protective effect of clozapine. Western blot analyses revealed that clozapine induced the phosphorylation of Akt and FoxO3a by the PI3K/Akt pathway and reversed the reduction of the phosphorylated Akt and FoxO3a and the nuclear translocation of FoxO3a evoked by corticosterone. Together, our data indicates that clozapine protects PC12 cells against corticosterone-induced cell death by modulating activity of the PI3K/Akt/FoxO3a pathway.
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PMID:The Atypical Antipsychotic Agent, Clozapine, Protects Against Corticosterone-Induced Death of PC12 Cells by Regulating the Akt/FoxO3a Signaling Pathway. 2717 57

Schizophrenia (SZ) is a mental disorder that involves cerebral and cerebellar abnormalities. The cerebellum plays an indispensable role in the pathophysiology of SZ. However, individual studies pertaining to the structural and resting-state functional cerebellar abnormalities in patients with SZ have been inconsistent. To make a relatively robust conclusion with little interference, such as different disease episode times and antipsychotic treatment, we conducted this meta-analysis as a first attempt to comprehensively analyze and combine studies of voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF), and functional connectivity strength (FCS) in first-episode and drug-naive SZ patients, employing the Seed-based d Mapping (SDM) method. Thirteen VBM studies, eight ALFF studies, and three FCS studies involving 783 patients and 704 matched healthy controls were included. Our results showed the presence of structural and functional abnormalities within the cerebellar regions, including most superior/anterior cerebellum (lobule III-V or VI) and posterior/inferior cerebellum (lobule VIII) related to motor function, and posterior cerebellum (lobule VIIa, Crus I, and II) associated with cognition and emotion, and such anomalies might be related to illness duration and clinical symptom severity.
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PMID:Cerebellar structural and functional abnormalities in first-episode and drug-naive patients with schizophrenia: A meta-analysis. 3050 Apr 74

Deficit schizophrenia (DS) is a distinct subtype of schizophrenia characterized by primary and enduring negative symptoms. More severe executive dysfunctions were observed in DS patients, however, the associated neuroimaging characteristics, especially cerebellar functional anomalies in DS, remain largely unknown. We employed resting-state functional and structural MRI data of 106 male participants, including data from 29 DS patients, 39 non-deficit schizophrenia (NDS) patients and 38 healthy controls (HCs). Z-standardized fractional amplitude of low-frequency fluctuation (zfALFF) values were calculated in order to examine spontaneous regional brain activity. Cerebro-cerebellar functional connectivity and changes in the volume of gray matter in the cerebellum were also examined. Relative to the HCs, both DS and NDS patients exhibited decreased zfALFF in the bilateral cerebellar lobules VIII and IX. The zfALFF in the left Crus II was lower in DS patients compared to NDS patients. No significant difference was observed in the volume of cerebellar gray matter among the three groups. Compared with NDS patients, cerebro-cerebellar functional connectivity analysis revealed increased connectivity in the left orbital medial frontal cortex and right putamen regions in DS patients. Reduced zfALFF in the left Crus II in the DS group was significantly positively correlated with Stroop Color and Word scores, while negatively correlated with Trail-Making Test part B scores. The increased functional connectivity in the right putamen in DS patients was significantly positively correlated with Animal Naming Test and semantic Verbal Fluency Test scores. These results highlight cerebellar functional abnormality in DS patients and provide insight into the pathophysiological mechanism of executive dysfunction.
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PMID:Aberrant cerebellar neural activity and cerebro-cerebellar functional connectivity involving executive dysfunction in schizophrenia with primary negative symptoms. 3061 42


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