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)

Enzymes concerned with neurotransmitter metabolism were measured postmortem in 50 regions from the brains of 11 chronic schizophrenics, 2 patients with senile dementia, 1 depressive, and 18 controls. Enzymes studied were tyrosine hydroxylase, dopa decarboxylase, glutamic decarboxylase, choline acetyltransferase (CAT), and acetylcholinesterase. The schizophrenic group had high CAT activities in the hippocampus, caudate, putamen, and nucleus accumbens; the other patients from the same hospital did not. A compensatory response to long- or short-term drug usage is considered, but correlations are hard to establish in the group studied. An alternative hypothesis proposes that the high levels are a compensatory response to defective cholinergic receptors in the affected areas. On this hypothesis, and by analogy with chorea, dopaminergic antagonists would act in schizophrenia by helping to reestablish cholinergic-dopaminergic balance.
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PMID:Possible changes in striatal and limbic cholinergic systems in schizophrenia. 4 82

1. PE is present in the brain in tiny quantities; it is heterogeneously distributed and present in synaptosomes. 2. It is synthesised from phenylalanine by L-AADC and oxidatively deaminated by MAO-B. Its turnover is remarkably fast. 3. Its concentration, particularly in the caudate nucleus, is affected by MAO inhibition (increased), lesion of the Substantia nigra (decreased), amine depletion (increased) and antipsychotic drugs (increased). 4. When iontophoresed (or injected) it amplifies the effects of DA and NA (and their agonists) but is without effect on other neurotransmitters. 5. It is suggested that it acts postsynaptically as a neuromodulator of catecholaminergic neurotransmission and that it is involved in the mechanism of action of Deprenyl; it is also suggested that it, or its principal metabolite PAA, may be involved in the aetiology of schizophrenia, depression and aggression as well as perhaps in other neuropsychiatric conditions.
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PMID:Phenylethylaminergic modulation of catecholaminergic neurotransmission. 165 28

Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.
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PMID:Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey. 613 May 56

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.
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PMID:Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man. 671 36

Using the reverse transcription-polymerase chain reaction (RT-PCR), we developed a sensitive and quantitative method to detect all four types of human tyrosine hydroxylase (TH) mRNAs in the human brain (substantia nigra). All four types of TH mRNAs were found in the substantia nigra in the control brains examined, and the ratio of type-1, type-2, type-3, and type-4 mRNAs to the total amount of TH was 45, 52, 1.4, and 2.1%, respectively. The average amount of total TH mRNA in the normal brain (substantia nigra) was 5.5 amol of TH mRNA per microgram of total RNA. The ratios of four TH isoforms were not altered significantly in Parkinson's disease or schizophrenia. Further we measured the relative amount of aromatic L-amino acid decarboxylase (AADC) and beta-actin mRNAs in the brain samples. TH and AADC mRNAs were highly correlated in the control cases. We found that parkinsonian brains had very low levels of all four TH isoforms and AADC mRNAs in the substantia nigra compared with control brains, while no significant differences were found between schizophrenic brains and normal ones. Since the decrease in AADC mRNA was comparable to that in TH mRNA, the alteration of TH in Parkinson's disease would not be a primary event, but it would reflect the degeneration of dopaminergic neurons in the substantia nigra. This is the first reported measurement of mRNA contents of TH isoforms and AADC in Parkinson's disease and schizophrenia.
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PMID:Quantification of mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the substantia nigra in Parkinson's disease and schizophrenia. 789 77

Over the last ten years, several positron emission tomography (PET) and single photon computerized tomography (SPECT) studies of the dopamine (DA) system in patients with schizophrenia were performed to test the hypothesis that DA hyperactivity is associated with this illness. In this paper, we reviewed the results of fifteen brain imaging studies comparing indices of DA function in drug naive or drug free patients with schizophrenia and healthy controls: thirteen studies included measurement of DA D2 receptors density, two studies compared amphetamine-induced DA release, and two studies measured DOPA decarboxylase activity, an enzyme involved in DA synthesis. We conducted a meta-analysis of the studies measuring D2 receptor density parameters, under the assumption that all tracers labeled the same population of D2 receptors. This analysis revealed that, compared to healthy controls, patients with schizophrenia present a significant but mild elevation of D2 receptor density parameters and a significant larger variability of these indices. We found no statistical evidence that studies performed with radiolabeled butyrophenones detected a larger increase in D2 receptor density parameters than studies performed with other radioligands, such as benzamides. Studies of presynaptic activity revealed an increase in DA transmission response to amphetamine challenge, and an increase in DOPA decarboxylase activity. Together, these data are compatible with both pre- and post-synaptic alterations of DA transmission in schizophrenia. Future studies should aim at a better characterization of these alterations, and at defining their role in the pathophysiology of the illness.
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PMID:Imaging dopamine transmission in schizophrenia. A review and meta-analysis. 979 69

This article will review the capabilities and accomplishments of radiotracer imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET) to measure pre-, post-, and "intra-synaptic" aspects of dopaminergic (DAergic) neurotransmission. The presynaptic site can be labeled with probes for the dopamine transporter (DAT) or the synthetic enzyme aromatic L-amino acid decarboxylase ("dopa decarboxylase"). The postsynaptic sites can be labeled with probes for either the dopamine D1 receptor (D1R) or the dopamine D2 receptor (D2R). The "synaptic" measurements are made indirectly by measurements of the interaction/displacement of receptor tracers by endogenous dopamine (DA). Agents are used which either release (e.g., amphetamine) or deplete (e.g., alpha-methyl-paratyrosine (AMPT), an inhibitor of tyrosine hydroxylase) tissue stores of DA. The application of these paradigms will be reviewed with special emphasis to neuropsychiatric diseases such as schizophrenia and idiopathic Parkinson's disease (IPD).
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PMID:Radiotracer imaging of dopaminergic transmission in neuropsychiatric disorders. 1063 81

Several lines of evidence implicate dopa decarboxylase (DDC) with schizophrenia. By analysis of two putative functional DDC variants in 173 schizophrenic patients and 204 controls we tested the hypotheses that DDC is involved in: (1) predisposition to schizophrenia; and (2) modulation of age at disease onset. No association was observed with schizophrenia as a whole, whereas an association between DDC genotypes and age at disease onset was suggested in males (P = 0.03). This association was most pronounced in relation to genotypes of haplotypes comprising both variants, suggesting an additive model where one variant mediates early and the other late onset. Accordingly, the haplotype-based genotypes could be assigned into three groups by their possible relative effect on age at onset: an "early", "neutral" and "late" group. Dividing the male schizophrenics into four groups with increasing age at onset, the "early" genotypes were seen to decrease in frequency from 51.5% to 16.7% while the "late" genotypes increased from 12.1% to 33.3% (P = 0.02). The difference in mean age at onset between male patients with "early" genotypes vs patients with "late" genotypes was close to 5 years (95% CI: 0.7-8.8). Thus, DDC may possibly act as a modulator of age at onset in male schizophrenics.
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PMID:Dopa decarboxylase genotypes may influence age at onset of schizophrenia. 1167

It has recently been reported that the human striatum, especially its ventral part, the nucleus accumbens, contains numerous neurons immunoreactive for aromatic L-amino acid decarboxylase (AADC; the second-step monoamine synthesizing enzyme), but not for tyrosine hydroxylase (TH; the first-step catecholamine synthesizing enzyme) or tryptophan hydroxylase (TPH; the first-step serotonin synthesizing enzyme). These AADC (+)/TH(-)/TPH(-) neurons are named D-neurons. AADC is also the rate-limiting synthesizing enzyme of phenylethylamine (PEA). Although the functions of striatal D-neurons are yet unclear, their functions were discussed in the present review based on recent findings in the literature. D-neurons may participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors, including L-dopa or droxidopa (L-threo-DOPS), and by converting them to dopamine (DA) or noradrenaline (NA), respectively. Because the nucleus accumbens is one of the brain regions involved in the pathogenesis of schizophrenia and drug dependence, D-neurons might be related to the etiology of these mental disorders. It has also been suggested that striatal D-neurons are the pluripotential cells that have compensating functions against aging or degeneration. Further studies should be conducted to elucidate the functions of this unique cell group in the human striatum.
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PMID:[Human striatal D-neurons and their significance]. 1237 66

It has recently been reported that the human corpus striatum, especially its ventral part, named as the nucleus accumbens, contains numerous non-monoaminergic aromatic L-amino acid decarboxylase (AADC; the second-step monoamine synthesizing enzyme) neurons (D-neurons). D-neurons are the neurons immunoreactive for AADC but not immunoreactive for dopamine or serotonin. They lack the first-step monoamine synthesizing enzymes, tyrosine hydroxylase and tryptophan hydroxylase. AADC is also the rate-limiting enzyme of phenylethylamine (PEA) synthesis. D-neurons might participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by uptaking monoamine precursors including L-dopa or droxidopa (L-threo-DOPS) and by converting them to dopamine or noradrenaline, respectively. As the nucleus accumbens is one of the brain regions that are involved in the pathogenesis of schizophrenia and drug dependence, D-neurons might be related to the etiology of these mental disorders. It has also been suggested that striatal D-neurons are the pluripotential cells that have compensating functions against aging or degeneration.
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PMID:[Localization of non-monoaminergic aromatic L-amino acid decarboxylase neurons (D-neurons) in the human striatum and their functional significance]. 1255 14


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