Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured the amount of Gi (the inhibitory G-protein) or Go (a similar G-protein of unknown function) in 5 areas of the medial temporal lobe of control and schizophrenic brains utilizing pertussis toxin-catalyzed ADP ribosylation. The material used has previously been shown to have asymmetrical structural abnormalities of the ventricular system. The amount of Gi or Go was reduced on the left side in the hippocampus, amygdala and parahippocampal gyrus, the difference reaching significance in the hippocampus. This data is the first report of a neurochemical correlate of the structural change in the brains of patients with schizophrenia. Decreased Gi or Go in hippocampus may relate to other reported neurochemical deficits or other transmembrane signalling abnormalities. Further investigations of these indices of secondary messenger function in relation to structural changes are indicated.
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PMID:G proteins (Gi, Go) in the medial temporal lobe in schizophrenia: preliminary report of a neurochemical correlate of structural change. 190 40

The neuronal dopamine transporter/uptake site can be covalently labeled with the photoaffinity probe 1-(2-[bis-(4-fluorophenyl) methoxy]ethyl)-4-[2-(4-azido-3-[125I]iodophenyl)ethyl]piperazine [( 125I]FAPP) and visualized following sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Upon photolysis, [125I]FAPP specifically incorporated into a polypeptide of apparent Mr = 62,000 in membranes from both the putamen and the caudate nucleus of control, Alzheimer's, schizophrenia, and Huntington's diseased brain, and following complete deglycosylation, migrated as an Mr approximately 48,000 polypeptide. In parkinsonian postmortem putamen, however, there was no detectable photoincorporation of [125I]FAPP into the ligand binding subunit of the dopamine transporter. [125I]FAPP did specifically label the Mr 62,000 polypeptide of parkinsonian caudate, although with efficiencies of 20-50% of control. The asymmetrical loss of the dopamine transporter in Parkinson's diseased striatum was confirmed in reversible receptor binding experiments using [3H]GBR-12935 (3H-labeled 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine). In parkinsonian putamen, mazindol competitively inhibited the binding of [3H]GBR-12935 with an estimated affinity (Ki approximately 2,000 nM) 10 times lower than in controls (Ki approximately 30 nM), while the affinity of maxindol for [3H]GBR-12935 binding in the caudate was equal to that seen with controls (Ki approximately 50 nM). The proportion of [3H]GBR-12935 binding sites recognized by mazindol with high affinity in Parkinson's diseased caudate was, however, reduced by 50-80%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. 198 18

It is probable that all schizophrenics have abnormalities in the medial temporal lobe, which differ in degree but not in kind. The structures of the medial temporal lobe are believed to have a crucial role in the integration and processing of the output from the association cortex. Dysfunction of this system could result in the clinical symptoms that form the core of the schizophrenia syndrome. The structural differences appear to fit the profile of a disturbance in the normal pattern of brain development. The asymmetrical patterns of normal brain development explain how such a disturbance simultaneously affecting both hemispheres could, disproportionately, affect the left (dominant) hemisphere. Epidemiological and pathological evidence points to aberrant genetic mechanisms as being the cause of the developmental anomaly in the majority of cases; environmental factors probably play a minor role. Despite the great progress made in solving the enigma of the structural changes in the brains of schizophrenics, the cause(s) of the changes--the aberrant genetic mechanism controlling brain development--may prove difficult to define.
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PMID:Schizophrenia: a neuropathological perspective. 201 55

Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A postmortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggest that the gene for psychosis is the 'cerebral dominance gene', the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short-arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition from Australopithecus through Homo habilis and Homo erectus to Homo sapiens.
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PMID:The continuum of psychosis and its genetic origins. The sixty-fifth Maudsley lecture. 227 27

With evidence that determinants of psychosis are present early and influence brain development, and in the absence of a significant environmental contribution, schizophrenia may be regarded as a genetic encephalopathy. Morphological abnormalities are particularly apparent in the temporal lobe and on the left side of the brain, and in a number of studies significant diagnosis x side interactions have been detected. Such interactions suggest an intimate relationship between the disease process and the mechanisms that determine asymmetrical brain development. These mechanisms presumably relate to the human capacity for speech and communication, and they may have played a critical role in the evolution of the human brain. A candidate locus for an asymmetry determinant and the psychosis gene within the exchange region of the sex chromosomes is proposed. Some sex differences in schizophrenia (e.g., with respect to age of onset and brain structure) may relate to subtle differences in the rate of asymmetry development in the two sexes.
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PMID:Temporal lobe asymmetries as the key to the etiology of schizophrenia. 228 33

The authors compared 21 "Kraepelinian" schizophrenic patients who had been ill and dependent on others for the past 5 years with 76 chronic schizophrenic patients in remission or with exacerbations requiring hospitalization. The Kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than the exacerbated patients, were less responsive to haloperidol, had more severe negative symptoms, and had similarly severe positive symptoms. They had cerebral ventricles that were more asymmetrical and a greater family history of schizophrenia spectrum disorders than the other chronic patients. These data suggest that patients with 5 years of illness and complete dependency on others may represent a subgroup of schizophrenia.
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PMID:Characteristics of very poor outcome schizophrenia. 360

The extent to which concordance rates for schizophrenia in monozygotic twins (between 36 and 58%) fall short of 100% is often taken as an index of the role of an environmental factor in schizophrenia, but such an agent remains elusive. That schizophrenic symptoms are observed in some viral illnesses suggests that schizophrenia might be due to a gene-virus interaction, but analysis of age of onset in pairs of siblings with the disease rules out horizontal transmission. An alternative hypothesis is proposed that onset of disease is due to the expression of a 'provirus', which is integrated in the genome, having been acquired either by prenatal infection or in the germ-line from an affected parent; this could explain why the season of birth effect is accentuated in, and perhaps confined to the group of patients without a family history of the disease. Germ-line integration is known to occur following infection with agents of the retrovirus class. Such agents can integrate at many sites in the host genome, but their interactions with proto-oncogenes (cellular genes which may act as growth factors) identify one type of integration site, and are associated with some of their pathogenic effects. Some characteristics of schizophrenic illness, particularly their selectivity for the dominant hemisphere, can be understood on the assumption that the virus (perhaps a retrovirus) responsible for the disease interacts with a proto-oncogene, which induces the asymmetrical brain growth responsible for laterality and cerebral dominance. The aetiologies of manic-depressive illness and schizophrenia may be related (the season of birth and onset effects are the same for the two conditions) and there is some evidence that the former transmutes into the latter in succeeding generations. The persistence of the functional psychoses may be due to the ability of the psychosis gene (or 'provirus') to induce change in the genetic mechanisms responsible for the development of laterality.
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PMID:A re-evaluation of the viral hypothesis: is psychosis the result of retroviral integration at a site close to the cerebral dominance gene? 608 45

Ten patients with the stable syndrome of hysteria were matched for age, sex, handedness, and full-scale WAIS IQ with ten controls, ten psychotic depressives and ten schizophrenics. All were subjected to an extensive neuropsychological test battery. Compared to the controls, the hysteria group exhibited bifrontal impairment (R = L) and, globally, greater dysfunction of the nondominant hemisphere. A G analysis provided a complete separation between the hysteria and controls. However, a D-index analysis showed that the hysteria group was more impaired than normals and depressives because of greater dysfunction of the dominant hemisphere, whilst schizophrenia showed greater nondominant hemisphere dysfunction than hysteria. Further, a cluster analysis on the 40 subjects produced three clusters: normal controls, depressives, and a schizophrenia-hysteria grouping. These findings are interpreted as suggesting that dominant hemisphere dysfunction is fundamentally related to the syndrome of hysteria and that the dysfunction of the nondominant hemisphere is brought about by associated features: the female excess, the emotional instability and dysphoric mood, the presence of asymmetrical pain, and conversion symptomatology. It is further argued, in view of the familial associations, that hysteria in the female is a syndrome equivalent to psychopathy in the male (who also exhibits dominant hemisphere dysfunction) and might represent in the female a (relatively benign) variant of schizophrenia characterized by imprecise verbal communications, a subtle form of affective incongruity, together with the conversion parameter.
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PMID:A neuropsychological study of the stable syndrome of hysteria. 727 78

Because electrodermal variables show consistency over time and situations, and evidence of genetic loading, it is of interest to examine such measures in adult schizophrenics and in children at risk for the disorder. Samples of adult schizophrenics are heterogeneous with regard to electrodermal activity. One group, the nonresponders, fails completely to respond to simple moderate intensity nonsignal stimuli. The other, the responders, does not differ from normals in frequency of response to nonsignal stimuli, but tends to show elevated tonic levels, and bilaterally asymmetrical and rapidly recovering responses. These two groups differ in other physiological and psychological measures, and in clinical picture. The responder pattern is predictive of poor outcome of acute schizophrenic episodes. A similar hyperactive pattern was found to differentiate children genetically at high or low risk for schizophrenia, and to predict psychiatric breakdown in the former group in Mednick and Schulsinger's original high risk study. The relationship to risk has been less evident in later studies, but similar, albeit weaker, tendencies have been reported. It is concluded that the nonresponding pattern may be secondary to a clinical picture of withdrawal and confusion, whereas the responder pattern may index vulnerability to schizophrenic episodes. On the psychological level, it is argued that this relationship is best conceptualized in attentional terms couched in information-processing language.
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PMID:Electrodermal activity and vulnerability to schizophrenia: a review. 733 75

Schizophrenia remains an enigmatic condition. It would appear that both genetic and environmental influences are relevant to the aetiopathogenesis of the disorder. Although a great amount of research has been carried out concerning the condition, the results have often lead to further questions and attempts to more closely delineate the object of study have lead to the originally observed findings becoming tenuous. One way to objectively view some aspects of this large body of work is to consider the condition as a cerebral situs inversus, as data from various lines of reasoning have suggested an inversion of the situation seen in normal controls. The hypothesis presented here draws on existing biological evidence to argue the likely role of light as a relevant, stimulatory variable which may interact with asymmetrical cerebral maturation in the establishment of functional laterality.
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PMID:If Schizophrenia is enantiomorphism, is light the morphogen? 867 58


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