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

Advances in psychopharmacology and neuroscience have brought into view a wide field of competing mechanisms for the etiology of schizophrenia including, but not limited to, deficits in one or more neurotransmitters (dopamine, serotonin, GABA, glutamate, and noradrenaline systems), neurodevelopmental defects in cortical connectivity, and viral infection. Genetic studies suggest heterogeneity in the illness, with multifactorial inheritance. Since cerebral metabolic activity reflects regional brain work for all neurotransmitter systems, imaging studies can provide information on the functional neuroanatomy of a deficit in the individual patient, allowing the grouping of patients for more intensive investigation in more homogeneous groups. Metabolic imaging studies allow psychopharmacological response to be regionally assessed and clinical responders to be identified, even for medications that affect more than one neurotransmitter system or have clinical effects that derive from changes in activity one synapse or more removed from the site of primary action.
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PMID:Positron emission tomography studies of abnormal glucose metabolism in schizophrenic illness. 758 18

Using a brain-dedicated triple-headed single-photon emission tomography (SPET) system, a sequential whole-volume imaging protocol has been devised to evaluate the regional distribution of iodine-123 iomazenil binding to GABAA receptors in the entire brain. The protocol was piloted in eight normal volunteers (seven males and one female; mean age, 24.8 +/- 3.9 years). The patterns obtained were largely compatible with the known distribution of GABAA receptors in the brain as reported in autoradiographic studies, with cerebral cortical regions, particularly the occipital and frontal cortices, displaying the highest 123I-iomazenil uptake. Measures of time to peak uptake and tracer washout rates presented with the same pattern of regional variation, with later times to peak and slower washout rates in cortical regions compared to other brain areas. Semiquantitative analysis of the data using white matter/ventricle regions as reference demonstrated a plateau of specific 123I-iomazenil binding in neocortical and cerebellar regions from 60-75 min onwards. These data demonstrate the feasibility of sequential, dynamic whole-volume 123I-iomazenil SPET imaging. The protocol may be particularly useful in the investigation of neuropsychiatric conditions which are likely to involve more than one focus of GABA abnormalities, such as anxiety disorders and schizophrenia.
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PMID:In vivo imaging of GABAA receptors using sequential whole-volume iodine-123 iomazenil single-photon emission tomography. 769 49

Schizophrenia is associated with structural changes in the brain but it is not clear whether the changes are localized. Studies in Manchester and elsewhere have reported abnormalities in biochemical markers of glutamate- and GABA-containing neurones in post-mortem brains from schizophrenic patients. The abnormalities occur in the ventral frontal cortex and anterior temporal lobe. It is suggested that these regions of the brain specifically encode information about social communication-language, gesture and facial expression. Many of the symptoms of schizophrenia become neuropsychologically understandable when seen as disturbances of social communication. In this and the following papers, experimental tests of this hypothesis are described.
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PMID:Neuropsychological implications of brain changes in schizophrenia: an overview. 784 46

Two patients with acute schizophrenic or schizo-affective psychosis were treated with benzodiazepine-monotherapy. In the first patient with paranoid-hallucinatory psychosis, catatonic symptoms disappeared completely after application of Lorazepam. Side effects of neuroleptic medication (neuroleptic turbulences) were the reason for benzodiazepine treatment in the second patient. In neither patients were psychotic symptoms observed during several weeks on benzodiazepine medication. Subsequently, no further neuroleptic treatment was necessary in one patient. Benzodiazepine effects on schizophrenia are probably caused by an activation of inhibitory GABA-ergic neurons. Besides stupor and catatonia, severe side effects of neuroleptic treatment or even contra-indications of neuroleptic medication may be an indication for benzodiazepine treatment in acute schizophrenia.
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PMID:[Benzodiazepine monotherapy in acute schizophrenia]. 790 19

A number of factors have been proposed as being linked to schizophrenia: genetic, psychological, endocrinological, metabolic, environmental, virological, and auto-immunological factors, as well as neurotransmitter systems and structural disorders of the brain. All may act as predisposing, triggering, or functionally modulating factors in what probably a condition composed of several types of disorder with varying aetiology. Neuroanatomical and neuromorphological data have revealed ventricular enlargement and diminished frontal and temporal lobe volume in some patients. These changes are concentrated particularly in the hippocampus/parahippocampal gyrus/amygdala, but are relatively small and span some overlap with healthy subjects. Twin studies suggest that at least some of these changes may result from other than genetic factors. Functional disturbances of the brain have also been connected with frontal and temporal structures in some schizophrenic patients. Of the single neurotransmitter substances, dopamine and serotonin appear to represent some of the central restitutive mechanisms whose function is to maintain mental stability; the understanding of their interplay with other neurotransmitters such as noradrenaline, acetylcholine, GABA, and glutamate, should provide a more integrated view of both normal and disturbed brain function.
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PMID:Biological factors in schizophrenia. Structural and functional aspects. 791 12

When a temporal gap is introduced between the offset of a central fixation point and the onset of a peripheral saccadic target, normal subjects generate an increased number of short latency (90-150 ms) saccades, termed express saccades, and the profile of express saccade frequency across different gap sizes for any individual subject, even if untrained in the task, shows a high test-retest reliability. In patients with schizophrenia, the generation of express saccades was also normal for gap sizes of 200-300 ms or in an overlap task (gap = 0 ms). However, for temporal gaps of 50-150 ms, the generation of express saccades was significantly impaired in the schizophrenic subjects. This selective deficit appeared to be independent of the patients' neuroleptic medication status and did not correlate with the severity of schizophrenic symptoms. It is postulated that the successful execution of an express saccade requires that the cognitive operations of disengagement of visual attention and selection of the appropriate motor command to generate a saccade both be commenced or completed during the temporal gap between fixation offset and peripheral target onset. Our results suggest that, in schizophrenia, there is an impairment in the cortical/subcortical neural network that generates express saccades and controls these cognitive operations. Potential sites for such dysfunction in schizophrenia include the parietal cortex and the GABA-ergic function of the superior colliculus.
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PMID:Selective impairment of express saccade generation in patients with schizophrenia. 815 54

Diazepam-binding inhibitor (DBI) is a 9-kD neuropeptide that interacts with the benzodiazepine (BZD) binding sites of the neuronal gamma-aminobutyric acid type A (GABAA) receptor and with the glial mitochondrial BZD receptor (MBR). We explored the involvement of CSF DBI-LI in schizophrenia, based on the potential role of GABA in the negative symptoms associated with schizophrenia, the relationship of its receptors with dopamine and norepinephrine release, and the proposed therapeutic efficacy of BZDs in schizophrenia. Clinical data, CSF DBI-LI and CSF monoamine measures were obtained in 65 drug-free male chronic (DSM-IIIR) schizophrenic patients, 53 of whom were also tested prior to haloperidol withdrawal. Following haloperidol withdrawal, CSF DBI-LI increased significantly. Drug-free CSF DBI-LI did not correlate with CSF monoamines. CSF DBI-LI was significantly higher in paranoid compared to chronic undifferentiated schizophrenic patients. The data suggest that DBI may have a symptom modulatory rather than an etiological role in schizophrenia.
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PMID:CSF diazepam binding inhibitor and schizophrenia: clinical and biochemical relationships. 827 78

Dopamine receptors are the principal targets of drugs used in the treatment of schizophrenia. Among the five mammalian dopamine-receptor subtypes, the D4 subtype is of particular interest because of its high affinity for the atypical neuroleptic clozapine. Interest in clozapine stems from its effectiveness in reducing positive and negative symptoms in acutely psychotic and treatment-resistant schizophrenic patients without eliciting extrapyramidal side effects. We have produced a subtype-specific antibody against the D4 receptor and localized it within specific cellular elements and synaptic circuits of the central nervous system. The D4-receptor antibody labelled GABAergic neurons in the cerebral cortex, hippocampus, thalamic reticular nucleus, globus pallidus and the substantia nigra (pars reticulata). Labelling was also observed in a subset of cortical pyramidal cells. Our findings suggest that clozapine's beneficial effects in schizophrenia may be achieved, in part, through D4-mediated GABA modulation, possibly implicating disinhibition of excitatory transmission in intrinsic cortical, thalamocortical and extrapyramidal pathways.
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PMID:Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. 862 68

In this paper schizophrenia is taken to be a collection of diseases with similar pathological features, including the core Bleulerian symptoms. The aim is to see how far current research can specify the anatomical regions which are functionally defective in schizophrenia and what transmitter systems may be involved. It appears schizophrenic brains show a tendency toward fewer cells in the temporal region, including limbic system as well as the thalamus. Functional deficits are seen in the dorsolateral frontal cortex, as well as thalamus suggesting a cortical-thalamic-striatal pathway. It is clear that Dopamine disregulation in this pathway leads to psychotic symptoms but probably does not account for the ambivalence, affective blunting or asocial behavior. GABA lesions prenatally could lead to glutamate over activity with potential toxic consequences after puberty leading to a plausible hypothesis as to the central neurochemical defect in schizophrenia, this hypothesis is elaborated.
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PMID:[Neurobiology of schizophrenia]. 865 3

The distribution, molecular structure and role of adenosine A2 receptors in the nervous system, is reviewed. The adenosine A2a receptor subtype, identified in the nervous system with ligand binding, functional studies or genetic molecular techniques, has been demonstrated in the striatum and other basal ganglia structures, in the hippocampus, in the cerebral cortex, in the nucleus tractus solitarius, in motor nerve terminals, in noradrenergic terminals in the vas deferens, in myenteric neurones of the ileum, in the retina and in the carotid body. The A2b receptors have been identified in glial and neuronal cells, and may have a widespread distribution in the brain. Activation of adenosine A2a receptors can enhance the release of several neurotransmitters, such as acetylcholine, glutamate, and noradrenaline. The release of GABA might be either enhanced or inhibited by A2a receptor activation. The A2 receptor activation also modulates neuronal excitability, synaptic plasticity, as well as locomotor activity and behaviour. The ability of A2 receptors to interact with other receptors for neurotransmitters/neuromodulators, such as dopamine D2 and D1 receptors, adenosine A1 receptors, CGRP receptors, metabotropic glutamate receptors and nicotinic autofacilitatory receptors, expands the range of possibilities used by adenosine to interfere with neuronal function and communication. These A2 receptor-mediated adenosine actions might have potential therapeutic interest, in particular in movement disorders such as Parkinson's disease and Huntington's chorea, as well as in schizophrenia, Alzheimer's disease, myasthenia gravis and myasthenic syndromes.
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PMID:Adenosine A2 receptor-mediated excitatory actions on the nervous system. 873 76


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