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

Recent postmortem investigations have suggested that schizophrenia may involve a defect in associative information processing in the upper layers of limbic cortex. One of these studies reported that vertical processes visualized with antibodies against the neurofilament 200K subunit (NFP-200K) of the axon cytoskeleton were increased in density in layer II and upper portions of layer IIIa of the cingulate region of schizophrenic individuals. Based on this latter finding, it was hypothesized that there may be a superbundance of associative afferents to this region. To explore this possibility further, an immunoperoxidase localization of the amino acid glutamate has been employed to visualize vertical fibers in layers II and IIIa of postmortem anterior cingulate cortex in both normal controls (n = 15) and schizophrenics (n = 17). Vertical fibers were distinguished according to small or large calibers and were differentially counted with a blind computer-assisted technique. The schizophrenic group showed a markedly higher density (77.8%) of small-caliber glutamate-immunoreactive vertical fibers when compared to controls; the density of large-caliber vertical fibers also showed a similar, though smaller (30.2%), increase in the schizophrenic group. There were no differences in the density of either small- or large-caliber processes in prefrontal cortex of the two groups. The effects of age, postmortem interval, fixation, and neuroleptic exposure do not account for the differences between the normal and schizophrenic subjects. Taking together their small caliber, vertical orientation, localization in superficial layers, and marked glutamate immunoreactivity, it seems plausible that the fibers showing an increased density in schizophrenics may be glutamatergic afferents, possibly ones that are associative in nature.(ABSTRACT TRUNCATED AT 250 WORDS)
Cereb Cortex
PMID:Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. 128 4

Regional cerebral blood flow (CBF) was studied in 51 young schizophrenics. A significant decrease of CBF was seen in frontal and prefrontal regions (hypofrontal pattern) in chronic patients whose disease had evolved for more than 2 years and who were in remission. This hypofrontal pattern was reversible, as it disappeared during exacerbation of the disease. In 10 patients who had not been treated with neuroleptics for several weeks, we found a dopaminergic hypersensitivity in the frontal lobes, as a weak dose of piribedil restored near-normal frontality. This may reflect either the role of neuroleptic washout or a primitive dopaminergic depletion, as proposed by some authors in the chronic form of schizophrenia.
J Cereb Blood Flow Metab 1987 Feb
PMID:Reversibility of hemodynamic hypofrontality in schizophrenia. 287 50

This article describes and partially validates a method for predicting whether an observed regional metabolic value is consistent with the observed value of another region. A regression equation was generated from a set of normal metabolic values, and then this equation was applied to patients with symptomatic Huntington's disease and patients at risk for this disorder. The results of the regression method were consistent with observations of the absolute rate for the normal subjects and Huntington's patients. For the at-risk patients, 6 of 18 were found to have reduced caudate metabolism relative to observed thalamic values. Since the initial scan, one of these identified at-risk individuals has developed symptomatic Huntington's disease. The method may be appropriate for other disorders where there are potential subgroups (e.g., schizophrenia) within a diagnostic category.
J Cereb Blood Flow Metab 1986 Dec
PMID:Regression model for predicting dissociations of regional cerebral glucose metabolism in individuals at risk for Huntington's disease. 294 6

The 2-deoxyglucose method was employed in rats following either acute or chronic administration of d-amphetamine. The drug was given either by a single intravenous and/or repeated daily intraperitoneal injections or by osmotic pumps implanted subcutaneously. Each mode of administration resulted in a specific constellation of metabolic effects. Acute doses of d-amphetamine, 5 mg/kg, stimulated glucose utilization in a number of cerebral structures, particularly the components of the extrapyramidal motor system. No effects were observed in components of the mesolimbic dopaminergic system. Repeated daily doses of 5 mg/kg for 2 weeks had no effects unless the dosage was progressively increased to toxic levels of 15 mg/kg over a 3-week period. Dosage sustained by osmotic pumps (12-15 mg/kg/day for 1 week or 6-7 mg/kg/day for 2 weeks), however, resulted in a selected increase in glucose utilization in the nucleus accumbens, an important component of the mesolimbic system. This finding may be of significance to the mechanism of amphetamine psychosis, which is sometimes regarded as a model of schizophrenia and is considered to be evidence in support of the dopamine hypothesis of the disease.
J Cereb Blood Flow Metab 1983 Jun
PMID:Comparative effects of acute and chronic administration of amphetamine on local cerebral glucose utilization in the conscious rat. 684 62

The classical cytoarchitectonic maps of human prefrontal areas produced by various cartographers in the early part of this century, though similar in gross topography, differ from one another in their descriptions of the size, shape, and precise location of specific regions within the frontal promontory. The current advances in human neurobiology stimulated us to reinvestigate the cytoarchitecture of the human prefrontal cortex, beginning with areas 9 and 46, to establish a set of objective cytometric criteria for identification of these areas. Nisslstained and Gallyas-stained celloidin-embedded sections were prepared from the left hemispheres of 17 human subjects 23-73 years old, without history of neurological disease. In eight cases, light microscopic observations were supplemented by morphometric data collected on a research microscope equipped with differential interference contrast optics and interfaced to a TV monitor with video mixing equipment and a microcomputer. We used the three-dimensional counting method of Williams and Rakic (1988) to measure (1) total cortical and relative laminar thickness, (2) neuronal packing density per 0.001 mm3 in individual cortical layers, and (3) sizes of neuronal somata in selected cortical layers. Light microscopic analysis confirmed that the cortical layers are more differentiated in area 46 than in area 9, particularly at the borders of layer IV. Layers III and V exhibit clearer sublamination in area 9, while layer IV is also somewhat wider in area 46 than in area 9 (9.3% vs 6.4% of cortical thickness); the overall thickness of the cortex is the same in both areas. Cytometric analysis revealed that layer IV neurons of area 46 are more densely packed than those in area 9 (55.38 +/- 7.26 vs 45.80 +/- 4.45 neurons/0.001 mm3), as are neurons in the supragranular layers II and III combined (53.51 +/ 6.33 vs 45.69 +/ 3.81 neurons/0.001 mm3). Finally, neurons in area 46 are more homogeneous in size than those in area 9. Differences in myeloarchitecture are also evident: each area contains numerous, well-stained radial striae and two pronounced bands of horizontal fibers, but in general, area 46 is less myelinated than area 9. Objective cytometric methods can clearly distinguish two adjacent areas within the human prefrontal lobe. These findings may prove useful in the areal parcellation of the human cerebral cortex as well as provide a baseline for analysis of pathological changes in neurological and psychiatric disorders such as a schizophrenia, Huntington's or Alzheimer's diseases.
Cereb Cortex
PMID:Cytoarchitectonic definition of prefrontal areas in the normal human cortex: I. Remapping of areas 9 and 46 using quantitative criteria. 758 Jan 24

Dopamine projections to the cerebral cortex have been implicated in normal and pathological cognitive processes, notably, Parkinson's disease and schizophrenia. To help elucidate the function of these dopamine axons, they were characterized by serial section electron microscopy in individual layers of monkey prefrontal cortex. Dopamine immunoreactivity was visualized with a silver precipitation technique that allowed clear resolution of the internal structures and cell membranes of labeled axons. Apart from the occasional large microtubule-filled axon, dopamine axons were thin and varicose with many clear synaptic vesicles and fewer dense-core vesicles. With few exceptions, dopamine synapses were symmetric and quite small, seen in only one to three serial sections. A determination of the "synaptic incidence" showed that only 39% of labeled varicosities formed identifiable synapses. However, it is certain that some small synapses could not be visualized even in serial sections, and it is possible that the vast majority if not all varicosities form synapses. Except for one soma, dendritic spines and shafts were the recipients of dopamine synapses. Many postsynaptic shafts were small and spiny, indicating that they were distal pyramidal dendrites. However, some postsynaptic shafts especially in supragranular layers had distinctly nonpyramidal features. These lacked spines, had a high density of synaptic inputs, and often had a strikingly varicose morphology. The data suggest that the majority of dopamine synapses in all layers are on pyramidal cells, but that a significant fraction are on presumed GABAergic nonpyramidal cells.
Cereb Cortex
PMID:Heterogeneous targets of dopamine synapses in monkey prefrontal cortex demonstrated by serial section electron microscopy: a laminar analysis using the silver-enhanced diaminobenzidine sulfide (SEDS) immunolabeling technique. 768 95

Dopamine has been implicated in the pathophysiology of schizophrenia, and the entorhinal cortex (ERC) is thought to be a site of structural pathology in this disorder. However, relatively little is known about the dopaminergic (DA) innervation of ERC in the primate brain. In this study, immunohistochemical methods and antibodies directed against tyrosine hydroxylase (TH) and dopamine were used to determine the organization of DA axons in the ERC of macaque monkeys. The anti-TH antibody used in this study appeared predominantly to identify DA axons, as demonstrated by its failure to label fibers that were immunoreactive with an antibody against dopamine-beta-hydroxylase in double-labeling experiments. In addition, the regional and laminar distributions of TH-immunoreactive fibers were strikingly similar to those labeled with the anti-dopamine antibody. With both antibodies, cytoarchitectonically identified subdivisions of monkey ERC (Amaral et al., 1987) differed in both the density and laminar distribution of labeled fibers. Immunoreactive processes exhibited a substantial rostral-to-caudal gradient of decreasing density across subdivisions of ERC, and the density of labeled fibers also decreased from medial to lateral in the rostral but not in the caudal subdivisions of ERC. The laminar distribution of labeled fibers differed both between and within subdivisions. For example, in the olfactory and rostral subdivisions of ERC, the superficial layers contained a very high density of immunoreactive processes, whereas in the intermediate region, three bands of labeled fibers were seen in layers I, III-IV, and VI. In addition, radial columns of fibers interdigitated with areas of decreased density were present between layers I and III. Although the overall density of labeled fibers was greater in lateral than in the caudal subdivisions of ERC, these regions had similar laminar distribution patterns. In these areas of monkey ERC, labeled processes were highest in density in deep layer I, and homogeneously distributed in the other cortical layers. These findings demonstrate that the DA innervation of monkey ERC is complex, and follows laminar- and subdivision-specific patterns. These patterns of distribution suggest the possible interactions that DA axons may have with other elements of ERC circuitry, and may provide insight into the possible functional roles of dopamine in ERC in both normal and disease states.
Cereb Cortex
PMID:The dopaminergic innervation of monkey entorhinal cortex. 790 2

In neuroimaging, functional mapping usually implies mapping function into an anatomical space, for example, using statistical parametric mapping to identify activation foci, or the characterization of distributed changes with spatial modes (eigenimages or principal components) (Friston et al., 1993a). This article is about a complementary approach, namely, mapping anatomy into a functional space. We describe a simple variant of multidimensional scaling (principal coordinates analysis; Gower, 1966) that uses functional connectivity as its metric. The scaling transformation maps anatomy into a functional space. The topography, or proximity relationships, in this space embody the functional connectivity among brain regions. The higher the functional connectivity, the closer the regions. Functional connectivity is defined here as the correlation between remote neurophysiological events. The technique represents a descriptive characterization of anatomically distributed changes in the brain that reveals the structure of corticocortical interactions in terms of functional correlations. To illustrate the approach we have analyzed data from normal subjects and schizophrenic patients obtained with PET during the performance of word generation tasks. In particular, we focus on prefrontotemporal integration in normal subjects and show that, in schizophrenia, the left temporal regions and prefrontal cortex evidence abnormal functional connectivity.
Cereb Cortex
PMID:Functional topography: multidimensional scaling and functional connectivity in the brain. 867 Jun 46

In a previous study of 10 drug-naive schizophrenic patients, the density of D2 dopamine receptors was found to be elevated in the caudate nucleus. The study raised questions about the influence of the age of the patients, the relationship of receptor density to psychosis, and the accuracy of the method used to obtain this evidence. Using positron emission tomography and constrained analysis of the brain uptake of the radioligand N-[11C]methyl-spiperone ([11C]NMSP), we tested four questions: Were the assumptions underlying the quantitation valid? Is there an age decline of the density of D2-like dopamine receptors in drug-naive schizophrenia and bipolar illness? If so, is it different from that observed in normal aging? Are D2-like dopamine receptors elevated at any age in either drug-naive schizophrenic or psychotic bipolar illness patients? NMSP and haloperidol partition volumes and plasma protein fractions were not significantly different among patient groups and normal volunteers. The model-derived assay of radioligand metabolites in plasma was confirmed by high-performance liquid chromatography in the patient groups. D2-like dopamine receptors declined with age, and the slope did not differ significantly between the schizophrenic patients, bipolar affective illness patients, and normal controls. Taking the effect of age into account, increases in D2 dopamine receptor density were found in seven psychotic patients with bipolar affective illness compared with seven nonpsychotic patients and 24 control subjects as well as in 22 drug-naive schizophrenic patients compared with the 24 control subjects.
J Cereb Blood Flow Metab 1997 Mar
PMID:Quantification of neuroreceptors in the living human brain: IV. Effect of aging and elevations of D2-like receptors in schizophrenia and bipolar illness. 911 6

The entorhinal cortex (ERC) has been implicated in the pathophysiology of Alzheimer's disease, schizophrenia and other disorders affecting cognitive functions. While powerful anatomical and histochemical methods (immunohistochemistry, in situ hybridization, etc.) may be applied (although with limitations) to postmortem human brain, each analysis should utilize a cytoarchitectonic approach to provide appropriate comparisons within the subdivisions of the ERC. Accordingly, we describe here the normal cyto- and myeloarchitecture of the human ERC as a prerequisite for the accompanying study of this region in schizophrenia. Our parcellation of this cortex differs from previous treatments in three ways. First, we adopted specific criteria of inclusion to define each subdivision of the region. Although distinctive ERC features are most prominent in the intermediate portion of this region, at least one of these features was considered the minimum necessary criterion to include adjacent tissue in the entorhinal area. Second, we used morphometric measurements (neuronal size and density as well as subdivisional volume and laminar thickness) to support our qualitative evaluation. Third, we have applied to the human ERC the conventional cytoarchitectonic nomenclature of the entorhinal cortex used previously in studies of non-human primates. This allows a more accurate extrapolation of the available numerous experimental anatomical, physiological and psychological data on this region to the human. As in the monkey, the five main subareas were recognized in the human (prorhinal, lateral, intermediate, sulcal and medial) but three required further subdivision (intermediate, sulcal and medial). The morphometric results obtained suggested a progression of the human entorhinal cortex from the peripheral to the central subareas, with the intermediate subarea (281) as the most complete entorhinal subdivision. Compared with non-human primates, the human ERC not only retains the basic periallocortical organization but also demonstrates further evolution. Taken together with available experimental data on the connectivity of this brain region, these results provide an anatomical basis for evaluating the ERC in human behavior.
Cereb Cortex 1997 Dec
PMID:The entorhinal cortex: an examination of cyto- and myeloarchitectonic organization in humans. 940 36


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