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)

Considerable evidence exists linking dopamine with schizophrenia. Other neurotransmitters including acetylcholine, serotonin and gamma-aminobutyric acid (GABA) are also being implicated. Neurotransmitters act via receptors on brain cells and evidence suggests that antipsychotic drugs exert their therapeutic actions and produce side effects by receptor blockade.
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PMID:Mayo Seminars in Psychiatry: dopamine and schizophrenia--a review. 3 63

Gamma-aminobutyric acid (G.A.B.A.) was measured in the nucleus accumbens and thalamus of brains from patients who had died with schizophrenia or Huntington's chorea (H.C.) and from control subjects. Mean G.A.B.A. content was significantly reduced in both brain areas in schizophrenia and in H.C. Extraneous factors, such as age, interval from death to necropsy, cause of death, and drug use, did not readily explain the observed reduction in brain G.A.B.A. G.A.B.A. deficiency may be a biochemical characteristic of some forms of schizophrenia.
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PMID:Gamma-aminobutyric-acid deficiency in brain of schizophrenic patients. 8 98

Neuroleptic (antipsychotic) drugs inhibited the electrically stimulated release of [3-H] dopamine from rat striatal slices. The concentrations for 50 percent inhibition (ranging from 11.5 nanomolar for spiroperidol to 800 nanomolar for thioridazine) correlated closely with the average daily dosages of 25 neuroleptic drugs used clinically for schizophrenia. The correlation includes butyrophenones, phenothiazines, reserpine, pimozide, clozapine, and (plus)- butaclamol. Clinically inactive isomers [trans-thiothixene, trans-flupenthixol, and (minus)-butaclamol] required 20 to 1000 times higher concentrations than the active isomers to inhibit release. Compared to the inhibition of [3-H] dopamine release, much higher neuroleptic concentrations were needed to inhibit the electrically stimulated release of other neurotransmitters--[3-H] acetylcholine, [3-H-a1 (gamma-aminobutyric acid). The neuroleptic drugs may block the presynaptic coupling between impulse and neurosecretion.
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PMID:Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. 114 94

The activity of gamma-aminobutyrate aminotransferase (GABA-T) was estimated in twelve regions of brains from 22 control subjects and 6 cases with schizophrenia. In the controls, no significant correlation was found between the enzyme activity and age or postmortem interval (PMI) in any of the brain regions studied. In experiments on rat brains, the enzyme activity decreased about 20% during the first 2 hours of storage at room temperature and at 4 degrees C but remained steady thereafter. A similar initial decline in activity in the human brain material cannot be excluded. In the human brains, a slightly lower activity was found in the group below 75 years (n = 8) when compared with the group above 75 years (n = 8). A tendency to higher activities was found in female brains (n = 10) compared with male brains (n = 12). No significant difference in the enzyme activity was found between schizophrenic brains, in any of the regions studied, when compared to controls, matched for age, sex and PMI.
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PMID:Gamma-aminobutyrate aminotransferase activity in brains of schizophrenic patients. 128 51

In a post-mortem study of schizophrenic and control subjects, the sodium-dependent binding of D-[3H]aspartate and [3H]nipecotic acid were used to investigate uptake sites of glutamate and gamma-aminobutyric acid (GABA), respectively, in subcortical brain regions. Binding to the glutamate uptake site was substantially reduced in both the putamen and lateral pallidum of the schizophrenic subjects. Binding to the GABA uptake site was substantially reduced in the putamen; smaller reductions were apparent in the caudate nucleus and lateral pallidum. The results suggest that glutamatergic and GABAergic mechanisms in the basal ganglia are abnormal in schizophrenia. These abnormalities could be relevant to the development of psychosis but could also relate to the spectrum of mild motor disturbances often described in the disease.
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PMID:Regionally selective deficits in uptake sites for glutamate and gamma-aminobutyric acid in the basal ganglia in schizophrenia. 135 92

Human fetal brain tissue was obtained from first-trimester elective abortions of two women who also had schizophrenia. Portions of the embryonic hippocampus or cerebral cortex were transplanted into the anterior eye chamber of immunologically compromised athymic nude rats. In this environment, embryonic brain tissue derived from normal women generally continues organotypic growth and development for many months. Although initial survival after transplantation was normal, the tissue derived from schizophrenic women manifested less robust growth. However, cells in the transplants showed typical neuronal differentiation, with development of different neuronal types, such as pyramidal cells, granule cells, and gamma-aminobutyric acid (GABA)-containing interneurons. Rhythmic electrical activity was also observed, indicative of some local synaptic organization. The presence of messenger RNA (mRNA) for brain-derived neuronotrophic factor (BDNF) was observed using in situ hybridization. The reason for the decreased rate of growth of these transplants remains unknown and the significance of the finding cannot be assessed from only two fetuses. However, these preliminary findings suggest that fetal transplants may be a useful model system for the detection of developmental pathogenic processes in the expression and transmission of schizophrenia.
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PMID:Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women. 136 85

A significant minority of patients with schizophrenia fail to respond to neuroleptic medication alone. In some of these patients, adjunctive treatment with benzodiazepines may prove beneficial. Preclinical studies suggest that benzodiazepines significantly decrease brain dopamine release and turnover, perhaps by augmenting gamma-aminobutyric acid (GABA) inhibition of dopamine neuron activity. Double-blind clinical studies, however, have not conclusively established a role for benzodiazepines in the treatment of schizophrenia, and it seems likely that some patients respond favorably, whereas others do not. We review preliminary new observations that approximately half of a group of treatment-resistant patients, studied in a double-blind treatment protocol, demonstrated clinically significant antipsychotic responses to adjunctive alprazolam. We also briefly describe long-term efficacy of alprazolam in several patients whom we have followed in open-label clinical settings. Possible predictors or biological concomitants of benzodiazepine responsivity, which may aid in delineating distinct subgroups of patients, are discussed, and recommendations for future research are presented.
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PMID:Benzodiazepine augmentation of neuroleptics in treatment-resistant schizophrenia. 136 77

Studies of amino acid release were carried out using frozen sections from brains of schizophrenics and controls. Synaptosomes were prepared via differential centrifugation in Ficoll allowing the veratridine-induced release of aspartate, glutamate, glycine, and GABA to be measured. The release of glutamate and gamma-aminobutyric acid (GABA) was reduced in the synaptosomes from schizophrenics. This decrease could be reversed partially by pre-incubation of the synaptosomes with haloperidol. Additionally, the activity of glutamate decarboxylase was decreased and partially restored by haloperidol pre-incubation. These data are consistent with the hypothesis of a glutamatergic/GABAergic deficit in schizophrenia.
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PMID:Evidence of glutamatergic deficiency in schizophrenia. 167 50

There is increasing evidence of a deficit or disturbance of neurons in the brains of schizophrenic patients--evidence that particularly implicates the frontal or temporal lobes. As yet there is no direct neurochemical correlate of the transmitter systems involved, although changes in some neurotransmitters in the temporal lobe have been reported. Radiolabeled nipecotic acid, a specific inhibitor of uptake sites to gamma-aminobutyric acid (GABA), has provided a marker of GABAergic neurons. The binding of this ligand to brain tissue taken at autopsy has demonstrated a decreased density of GABA uptake sites in the hippocampus in schizophrenia. This decrease was found to correlate in the left hemisphere with increased concentration of dopamine in the amygdala, providing a link between neuropathology, evidence of laterality, and the dopamine hypothesis of the disease.
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PMID:Deficit and hemispheric asymmetry of GABA uptake sites in the hippocampus in schizophrenia. 215 50

We measured the contents of gamma-aminobutyric acid (GABA) and of other amino compounds in five regions of autopsied brain from 18 patients with schizophrenia and from a large group of adult control subjects dying without any neurological or psychiatric disorder. In addition, concentrations of GABA were measured in the cerebrospinal fluid (CSF) of living schizophrenic patients and control subjects. No deficiency of GABA was found in the frontal cortex, caudate nucleus, putamen, nucleus accumbens, or medial dorsal thalamus of patients dying with schizophrenia, nor were GABA concentrations low in the CSF of living schizophrenic patients. These results do not confirm our earlier report of low levels of GABA in the nucleus accumbens and thalamus of some schizophrenic patients. We do not find neurochemical evidence favoring an involvement of GABAergic neuronal hypofunction in the etiology either of schizophrenia or of neuroleptic-induced tardive dyskinesia.
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PMID:Schizophrenia, tardive dyskinesia, and brain GABA. 256 86


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