Schizophrenia as a Brain Disease

Williamson, Peter C.

doi:10.1001/archneur.1993.00540100081021

Cited by 8 publications

(3 citation statements)

References 16 publications

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“…Despite a number of suggestive ndings, there is currently no proof that a global abnormality of neuro-transmission is a primary feature of schizophrenia Mesulam, 1990;Williamson, 1993;Carpenter & Buchanan, 1994]. Modeling Stevens' theory, we have focused on neuroanatomical synaptic changes, without referring to any speci c neurotransmitter.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Schizophrenic Delusions and Hallucinations: A Neural Model

Ruppin¹,

Reggia²,

Horn³

1996

Schizophrenia Bulletin

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We implement and study a computational model of Stevens' theory of the pathogenesis of schizophrenia. This theory hypothesizes that the onset of schizophrenia is associated with reactive synaptic regeneration in brain regions that receive degenerating temporal lobe projections. Concentrating on one such area, the frontal cortex, we model a frontal module as an associative memory neural network whose input synapses represent incoming temporal projections. Modeling Stevens' hypothesized pathological synaptic changes in this framework results in adverse side effects similar to hallucinations and delusions seen in schizophrenia: spontaneous, stimulus-independent retrieval of stored memories focused on just a few of the stored patterns. These could account for the delusions and hallucinations that occur in schizophrenia without any apparent external trigger and for their tendency to concentrate on a few central cognitive and perceptual themes. The model explains why the positive symptoms of schizophrenia tend to wane as the disease progresses, why delayed therapeutic intervention leads to a much slower response, and why delusions and hallucinations may persist for a long time when they do occur.

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of Schizophrenic Delusions and Hallucinations: A Neural Model

Ruppin¹,

Reggia²,

Horn³

1996

Schizophrenia Bulletin

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“…Several laboratories establish a case for glutamates in the etiology of schizophrenia [Carlson and Carlson, 1990;Javitt and Zukin, 1991;Simpson et al, 1992;Williamson, 1993;Debonnel, 1993;Ulas and Cotman, 1993;Olney and Farber, 19941. Data suggest that abnormalities of NMDA function may relate to the pathophysiology of schizophrenia, in that the drug, phencyclidine (PCP), produces psychotic symptoms that mimic schizophrenia by blocking NMDA-gated ion channels.…”

Section: Contiguity Of Retinoid Gene and Psychosis Gene Vs Retinoid mentioning

confidence: 99%

Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

Goodman

1995

Am. J. Med. Genet.

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Vitamin A (retinoid), an essential nutrient for fetal and subsequent mammalian development, is involved in gene expression, cell differentiation, proliferation, migration, and death. Retinoic acid (RA) the morphogenic derivative of vitamin A is highly teratogenic. In humans retinoid excess or deficit can result in brain anomalies and psychosis. This review discusses chromosomal loci of genes that control the retinoid cascade in relation to some candidate genes in schizophrenia. The paper relates the knowledge about the transport, delivery, and action of retinoids to what is presently known about the pathology of schizophrenia, with particular reference to the dopamine hypothesis, neurotransmitters, the glutamate hypothesis, retinitis pigmentosa, dermatologic disorders, and craniofacial anomalies.

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“…Abnormalities in glutamatergic synaptic transmission have been implicated in many neuropathologies, including certain seizures, ischemia-induced neuronal death, schizophrenia, Alzheimer disease, Parkinson disease, and Huntington disease (7)(8)(9)(10)(11). Excessive release of glutamate into the synaptic cleft is believed to be a common underlying basis for many of these disease states.…”

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confidence: 99%

A protein factor that inhibits ATP-dependent glutamate and γ-aminobutyric acid accumulation into synaptic vesicles: Purification and initial characterization

Özkan

Lee

Ueda

1997

Proc. Natl. Acad. Sci. U.S.A.

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Glutamate, the major excitatory neurotransmitter in the mammalian central nervous system, is transported into and stored in synaptic vesicles. We have purified to apparent homogeneity a protein from brain cytosol that inhibits glutamate and ␥-aminobutyric acid uptake into synaptic vesicles and have termed this protein ''inhibitory protein factor'' (IPF). IPF refers to three distinct proteins with relative molecular weights of 138,000 (IPF ␣), 135,000 (IPF ␤), and 132,000 (IPF ␥), respectively. Gel filtration and sedimentation data suggest that all three proteins share an elongated structure, identical Stokes radius (60 Å), and identical sedimentation coefficient (4.3 S). Using these values and a partial specific volume of 0.716 ml͞g, we determined the native molecular weight for IPF ␣ to be 103,000. Partial sequence analysis shows that IPF ␣ is derived from ␣ fodrin, a protein implicated in several diverse cellular activities. IPF ␣ inhibits ATP-dependent glutamate uptake into purified synaptic vesicles with an IC 50 of Ϸ26 nM, while showing no ability to inhibit ATP-independent uptake at concentrations up to 100 nM. Moreover, IPF ␣ inhibited neither norepinephrine uptake into chromaffin vesicles nor Na ؉ -dependent glutamate uptake into synaptosomes. However, IPF ␣ inhibited uptake of ␥-aminobutyric acid into synaptic vesicles derived from spinal cord, suggesting that inhibition may not be limited to glutamatergic systems. We propose that IPF could be a novel component of a presynaptic regulatory system. Such a system might modulate neurotransmitter accumulation into synaptic vesicles and thus regulate the overall efficacy of neurotransmission.

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Schizophrenia as a Brain Disease

Cited by 8 publications

References 16 publications

Pathogenesis of Schizophrenic Delusions and Hallucinations: A Neural Model

Pathogenesis of Schizophrenic Delusions and Hallucinations: A Neural Model

Chromosomal locations and modes of action of genes of the retinoid (vitamin A) system support their involvement in the etiology of schizophrenia

A protein factor that inhibits ATP-dependent glutamate and γ-aminobutyric acid accumulation into synaptic vesicles: Purification and initial characterization

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