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)

The concentrations of serum tyrosine, phenylalanine and tryptophan have been determined in 23 male neuroleptic-free patients with schizophrenia and 28 male healthy control subjects. Tyrosine was significantly lower in neuroleptic-free patients with an early onset (starting before adulthood) than in healthy control subjects (p < 0.05), and the ratio of tyrosine to phenylalanine was significantly lower in neuroleptic-free patients with an early onset than in those with a late onset (starting at adulthood). No significant differences in these three amino acids were found between the patients with a late onset and healthy control subjects. The present findings suggest that there may be a disturbance of balance between tyrosine and phenylalanine in early-onset patients with schizophrenia.
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PMID:Low concentrations of serum tyrosine in neuroleptic-free schizophrenics with an early onset. 776 38

Circadian rhythm abnormalities have been described mostly with respect to manic-depressive illness; little information is available concerning circadian rhythms and schizophrenia or their influence on neuroleptic drugs. We showed previously that the MESOR of dopamine is higher in schizophrenic patients than in healthy subjects and that women who are drug-free schizophrenic have lower prolactin MESORs and lower amplitudes than healthy women. We now report the data of a cosinor analysis of tryptophan, serotonin, melatonin, and pituitary hormones in the blood of 34 healthy subjects, 90 drug-free schizophrenics, and 25 neuroleptic-treated schizophrenic patients. This data indicated a significant phase advance of serum tryptophan, prolactin, and melatonin concentrations, a trend toward a phase advance in serotonin. Thyroid stimulating hormone (TSH), and growth hormone concentrations, and decreases in the TSH MESORs among patients compared to healthy subjects. These results suggest that circadian changes, such as phase advances and alterations in MESOR, are not only present in depression but also in schizophrenia. Although neuroleptic treatment raised the prolactin MESOR and amplitude, it did not elicit any change in circadian rhythmicity among the other parameters.
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PMID:Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. 790 93

Recent hypotheses and findings indicate that measurements of interactions between cerebrospinal fluid (CSF) biogenic amine systems, rather than measurement of CSF biogenic amine metabolites, better correlate with clinically important findings in schizophrenia. To test hypotheses, we used a recent technological advance in high performance liquid chromatography with electrochemical detection and combined it with multivariate statistical analyses to study biogenic amine concentrations in CSF in schizophrenia. This approach enabled the study of the interactions of several metabolites of each of the three major neurotransmitter pathways (dopaminergic, noradrenergic, and serotonergic) to test existing hypotheses regarding the neurobiochemical basis of schizophrenia. Twenty biogenic amines, their metabolites, and other compounds from 24 medication-free schizophrenic patients and 12 normal control subjects were simultaneously measured using a recently developed technique of gradient high performance liquid chromatography coupled with a 16-channel electrochemical array detector. After covariation for storage time, results of a stepwise discriminant function analysis comparing the control and patient groups identified tryptophan, tryptophol, and epinephrine as discriminating variables. Hotelling's paired T2 test from a subgroup of schizophrenic patients studied while they were and were not receiving neuroleptic treatment did not yield any significant differences between subgroups. A discussion of the findings and a comparison with previous studies of CSF biogenic amines in schizophrenia are presented.
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PMID:A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: I. Comparisons with healthy control subjects and neuroleptic-treated/unmedicated pairs analyses. 799 18

As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia.
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PMID:A multidimensional approach to analysis of cerebrospinal fluid biogenic amines in schizophrenia: II. Correlations with psychopathology. 799 19

1. Evidence suggests catecholamines and indoleamines may play a role in the pathogenesis of several psychiatric disorders. These neurotransmitters (i.e. dopamine, norepinephrine and serotonin) are synthesized within the human brain from their precursors, the aromatic large neutral amino acids tyrosine and tryptophan. Other large neutral amino acids, namely valine, isoleucine, leucine and phenylalanine affect precursor availability by competing with tryptophan and tyrosine for the transport system across the blood brain barrier. 2. The authors evaluated the brain availability of L-tryptophan and tyrosine in a sample of psychiatric patients with a diagnosis of major depression and schizophrenia. 3. The present results suggest a possible usefulness of Tryptophan/Large Neutral Amino Acids ratio in distinguishing major depression from schizophrenia, while Tyrosine/Large Neutral Amino Acids ratio shows a very limited usefulness. The absolute need of powerful and accurate statistical analysis to evaluate the power of a biological test clearly stands out from the present study.
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PMID:Neutral amino acid availability in two major psychiatric disorders. 858 60

Because brain serotonin levels depend directly on the amounts of exogenous tryptophan (TRP) available for its synthesis, amounts of TRP in the diet may be manipulated to alter the corresponding levels of serotonin. This technique has been used for probing the role of serotonin in mediating various forms of pyschopathology. In this study, 16 patients meeting DSM III-R criteria for schizophrenia (n = 14) or schizoaffective disorder (n = 2) were assessed for the effects of acute dietary TRP depletion under controlled conditions. The hypothesis was that lowering of serotonin would result in a diminution of 'positive' and/or 'negative' symptoms of psychotic disorders. No clinically or statistically significant improvement compared to baseline occurred when TRP depletion was imposed. Indeed, there was a statistically significant deterioration on measures of negative symptoms. The results are discussed in the context of the methodological issues.
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PMID:Acute dietary tryptophan depletion: effects on schizophrenic positive and negative symptoms. 901 17

The brain-rich 14-3-3 protein regulates synthesis and excretion of bioamine by activating tyrosine and tryptophan hydroxylases, and by exocytosis of catecholamines and serotonin. In humans, at least eight subunits of the 14-3-3 protein family have been isolated. The 14-3-3 eta chain gene is located at 22q12.1 to q13.1, one of the chromosome regions identified as possibly linked to schizophrenia. We systematically searched for nucleotide variants in the coding region, 5' and 3' untranslated region, and in the exon-intron boundaries of the genomic 14-3-3 eta gene in 24 schizophrenics and 24 controls. Two polymorphic sites were found: one in the 5' untranslated region and one in the 3' untranslated region. However, no variants predicting amino-acid alterations were observed. Similar allelic and genotypic distributions for both polymorphisms were found in 308 schizophrenics and 135 controls.
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PMID:Systematic search for mutations in the 14-3-3 eta chain gene on chromosome 22 in schizophrenics. 956 86

Serotonin is a key neurotransmitter in the central nervous system, and dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex psychiatric diseases. Polymorphisms of many of the genes involved in serotonin biosynthesis, catabolism, and response have been reported, suggesting that genetic variability may underlie the development of diseases such as schizophrenia, obsessive compulsive disorder, and suicide. A number of single-gene polymorphisms in serotonergic pathways have been examined in these and other diseases, but to date results from this candidate gene approach have been disappointing. Although this may be because the detection of a small effect may require the analysis of large numbers of patients and controls, an alternative explanation is that the clinical importance of a single subtle genetic variant may be overlooked unless other functionally related genes are studied in tandem. To facilitate an integrated analysis, we have developed a PCR-SSP-based assay that permits the simultaneous genotyping of 13 single nucleotide polymorphisms in 9 serotonergic genes under identical conditions. These genes include tryptophan hydroxylase, tryptophan dioxygenase, monoamine oxidase A, and the serotonin receptors 5HT1A, 5HT1D-alpha, 5HT1D-beta, 5HT2A, 5HT2C, and 5HT5A. Using this technology, we have genotyped 100 Caucasoid control individuals and demonstrate that this approach is reliable, quick, cheap, and easy to interpret. We anticipate that this will facilitate the analysis of the genetic basis of susceptibility and phenotypic variability of a number of complex psychiatric diseases. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:621-627, 1999.
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PMID:Unified approach to the analysis of genetic variation in serotonergic pathways. 1058 80

Previous work from this laboratory had demonstrated the presence of endogenous morphine, strychnine and nicotine in the mammalian brain and human serum samples. Morphine is synthesised from tyrosine and strychnine and nicotine from tryptophan. This study examines the role of strychnine, nicotine and morphine in neuropsychiatric disorders. The blood levels of tyrosine, tryptophan, strychnine, nicotine and morphine were studied as also RBC membrane Na(+)-K+ ATPase activity. It was found that serum tyrosine levels were reduced and tryptophan levels elevated in all neuropsychiatric disorders studied with a reduction in RBC Na(+)-K+ ATPase activity. Nicotine was present in significant amounts in serum of patients with schizophrenia, CNS glioma and syndrome X with multiple lacunar state. Morphine was present in significant amounts only in the serum of patients with multiple sclerosis and MDP. Strychnine was present in significant amounts in the serum of patients with epilepsy, Parkinson's disease and MDP. The presence of nicotine and strychnine in significant amounts could be related to elevated tryptophan levels suggesting the synthesis of these alkaloids from tryptophan. Morphine was not detected in most of the disorders owing to low tyrosine levels noted in them. Na(+)-K+ ATPase inhibition noticed in most of the disorders could be related to decreased hyperpolarising morphinergic transmission and increased depolarising nicotinergic and strychinergic transmission. The role of morphine, strychnine and nicotine in the pathogenesis of these disorders in the setting of membrane Na(+)-K+ ATPase inhibition is discussed.
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PMID:Endogenous strychnine, nicotine, and morphine--description of hypo and hyper-strychninergic, nicotinergic and morphinergic state in relation to neuropsychiatric diseases. 1111 26

The administration of the N-methyl-D-aspartate (NMDA)-associated glycine recognition site agonist D-cycloserine (DCS) to rats inhibited the head shakes and the forepaw treading induced by the serotonin (5HT) precursor, L-5-hydroxy-tryptophan [(-)5HTP], as well as the forepaw treading and motility elicited by the selective 5HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). The head shakes typically induced by the 5HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), were unaffected by DCS pretreatment. The results are consistent with reduced serotonergic transmission produced by NMDA activation, as suggested by other authors. Due to the important role played in the pathogenesis of schizophrenia by glutamate deficiency/serotonin activation, the results support the view that positive modulators of NMDA receptors, activating glutamate receptors and reducing serotonergic tone, might be useful in the alleviation of psychotic symptoms. However, because of its partial agonist properties at the glycine recognition site, D-cycloserine shows some effects that might make it unsuitable for clinical use.
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PMID:D-Cycloserine, a positive modulator of NMDA receptors, inhibits serotonergic function. 1119 34


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