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)

Compared to healthy controls, unmedicated schizophrenic patients had significantly higher plasma concentrations of taurine, methionine, valine, isoleucine, leucine, phenylalanine, and lysine. Except for taurine, these amino acids share the L-transport system for neutral amino acids. In the patients, homovanillic (HVA) acid levels in CSF were decreased and the plasma levels of the amino acids competing with tyrosine and tryptophan for transport into the brain, were all negatively correlated to the CSF concentrations of HVA and 5-HIAA. These findings could be explained by a change in the affinity of the L-system or by a decrease in its overall capacity in schizophrenia. Raised plasma levels of the competing amino acids may limit the brain uptake of tyrosine, leading to a diminished dopamine turnover, and resulting in a compensatory development of supersensitive dopamine receptors.
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PMID:Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls. 241 98

The authors have investigated the levels of free amino acids and of the total fraction of medium molecules in the blood serum of patients with the paranoid form of continuously progressive schizophrenia. It has been demonstrated that these parameters are different in clinically normal individuals versus schizophrenics. The concentrations of free amino acids were the highest in people aged 40 to 50 years (Cys, Ala, Lys, Asp, Thr, Tyr, Try, Val, Leu, Ile) being considerably lower in individuals aged 50 to 60 years (Cys, Ala, Tyr) and over 60 years (Lys, His, Asp, Tyr, Try) which corresponds to the highest activity of the process in patients aged 40 to 50 years and its stabilization in older age.
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PMID:[Free amino acids and the total middle molecule fraction of the blood serum in patients with continuously progressive paranoid schizophrenia undergoing treatment]. 336 87

Among the biochemical theories proposed for schizophrenia the best-founded appears to be the dopaminergic theory. Dopaminergic agonists exacerbate schizophrenic symptoms. Neuroleptics, which are the most effective drugs in schizophrenia, are dopaminergic-blocking agents. Other biochemical disorders have been demonstrated in some cases of schizophrenia but results are not always consonant. The presence of abnormal compounds, i.e. methylated derivatives or phenylethylamine, has often been mentioned. Several disorders of enzymes have also been reported, such as a defect in beta-dopamine hydroxylase or an abnormal activity of the MAO which metabolizes the indolamines and catecholamines. Disorders of the metabolism of noradrenaline and serotonin have also been suggested, mainly on experimental evidence. Other compounds have been incriminated, such as endorphins, gamma-aminobutyric acid, lysine-8 vasopressin or prostaglandins. The action of neuroleptics can be ascribed to dopaminergic respector blockade, as a safe approximation. However, the demonstration of several dopaminergic pathways and of several types of receptors makes the understanding of their mode of action all the more difficult that they interplay with many other neurotransmittors.
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PMID:[Biochemistry of schizophrenia and mechanism of action of neuroleptics]. 613 Jun 4

Sixteen out of 19 patients suffering from chronic anergic schizophrenia completed a placebo-controlled cross-over study with lysine-8-vasopressin (LVP), following a schedule of 1 week of placebo, 3 weeks of LVP, starting with 22.5 IU/day, gradually increased to 67.5 IU/day, and finally 4 weeks of placebo. The psychic state was evaluated with the Brief Psychiatric Rate Scale (BPRS), during weekly live interviews, and following videotaped BPRS interviews at the beginning and end of the LVP period, and at the end of the final placebo period. Symptoms of parkinsonism and tardive dyskinesia were also videotaped during a standardized examination at the same intervals. The videotapes were subsequently randomized and evaluated blindly. The results of liver interviews showed a significant (P less than 0.05) decrease in the BPRS anergic factor after 2 and 3 weeks of LVP treatment, but there were no changes in any single item, other BPRS factors, or the BPRS total score. The results of the videotape evaluations showed that the BPRS thinking disorder factor was significantly (P less than 0.05) decreased after 3 weeks of LVP, whereas the BPRS score was unchanged. No consistent changes in parkinsonism or tardive dyskinesia were found. Although side effects were few, six patients became agitated or aggressive during the LVP treatment. The beneficial effect on thought disorder and anergia, but the absence of global effects on the schizophrenic syndrome, illustrates the need for further research with other vasopressin analogues. The advantages and disadvantages of live and videotaped psychiatric interviews are also discussed.
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PMID:Vasopressin in anergic schizophrenia. A cross-over study with lysine-8-vasopressin and placebo. 679 86

Neurotensin (NT, pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) is a tridecapeptide that displays a wide spectrum of biological actions. Cyclic derivatives of a hexapeptide NT [(8-13)] (N alpha MeArg-Lys-Pro-Trp-Tle-Leu, Tle = tert-leucine) were designed and prepared by a combination of solution and solid-phase peptide synthetic methodologies. As reported previously, several analogs possessed nanomolar binding affinities for NT receptors in newborn (10-day-old) mouse brain membrane preparations. In this study, we determined the functional ability of these analogs to mobilize intracellular free calcium, [Ca2+]i, in HT-29 cells (human colonic adenocarcinoma). Of greatest interest were the cyclic compounds 2, 6 and 9 that had Ki values of 0.19, 3.50 and 4.18 microM for [3H]NT labeled receptors in the HT-29 cell membrane assay, respectively. In the functional assay, compounds 2 and 6 mobilized [Ca2+] with EC50 values of 0.13 and 20 microM, respectively. In comparison, Compound 9 blocked the NT-induced mobilization of [Ca2+]i, with an IC50 of 1.70 microM. The present findings indicate that small molecule cyclic analogs, that possess functional activity, can be designed and may have therapeutic utility in the treatment of schizophrenia and possibly other neurological disorders.
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PMID:Functional activity of new C-terminal cyclic-neurotensin fragment analogs. 881 44

In the present study, we evaluated the possible contribution of genetic variation of the serotonin 5-HT7 receptor to the development of schizophrenia and bipolar affective disorder. Cloning and characterization of exon-flanking intronic sequences enabled us to investigate the whole coding region and the exon-intron boundaries of the human 5-HT7 receptor gene. Using single-strand conformational analysis, we screened for presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic and 46 bipolar affective patients, as well as 46 healthy controls. We detected two rare naturally occurring receptor variants (Pro-279-Leu, Thr-92-Lys) and a silent nucleotide substitution (A-->G) at position +1233. The occurrence of the Pro-279-Leu and Thr-92-Lys substitutions was studied in an extended sample of patients (n = 462) and controls (n = 335). The Leu-279 variant was found in similar frequency in all groups, indicating that presence of this variant is not causally related to the development of schizophrenia or bipolar affective disorder. The Lys-92 variant was found in a single individual who suffered from bipolar affective disorder. Investigation of the patient's family revealed independent segregation between the Lys-92 variant and psychiatric illness. Our data suggests that genetic variation of the 5-HT7 receptor does not play a major role in the development of bipolar affective disorder and schizophrenia.
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PMID:The human serotonin 7 (5-HT7) receptor gene: genomic organization and systematic mutation screening in schizophrenia and bipolar affective disorder. 915 33

Mutation screening identified variants of h5-HT1A (Gly-22-Ser, Ile-28-Val, Arg-219-Leu), h5-HT1B (Phe-124-Cys), h5-HT2A (Thr-25-Asn, His-452-Tyr), h5-HT2C (Cys-23-Ser) and h5-HT7 (Thr-92-Lys, Pro-279-Leu) receptors. Screening of h5-HT1D, h5-ht1e, h5-ht1f and h5-ht5 receptor genes failed to detect any significant mutations. No differences in radioligand binding properties were observed between the h5-HT1A Ile-28-Val variant receptor (VR) and the wildtype receptor (WTR). Binding profiles of the h5-HT1A Gly-22-Val variant and the WTR were also very similar, but the 8-OH-DPAT-induced down-regulation and desensitization of the VR was attenuated. The h5-HT1B Phe-124-Cys variant leads to considerable changes in [3H]5-carboxamidotryptamine binding: Bmax was decreased and the affinity of various h5-HT1B ligands was modified (usually increased; e.g., in the case of sumatriptan). The h5-HT2A His-452-Tyr variant causes an alteration of the amplitude and timing of intracellular calcium mobilization in platelets from 452-His/452-Tyr heterozygous compared to 452-His/452-His homozygous individuals. Most, but not all, of the VRs listed above were examined for association with, e.g., bipolar depression and schizophrenia, yet no relation was observed. The most consistent finding was an association between a silent mutation (102T/C) in the h5-HT2A receptor gene and schizophrenia; this association may be explained by linkage disequilibrium with a functional variant in the regulatory region of the gene. Studies of the therapeutic response to clozapine produced no homogeneous results with respect to the pharmacogenetic significance of the various mutations in the h5-HT2A and h5-HT2C receptor genes.
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PMID:Genetic variation in human 5-HT receptors: potential pathogenetic and pharmacological role. 992 35

1. There has been considerable research in the field of schizophrenia over the past few years with emphasis on the discovery of better drugs, particularly those with 5-HT2 antagonist activity. 2. In an effort to enhance identification of such compounds and to further understand the contribution of 5-HT2 activity to the effects of antipsychotic drugs, a series of conventional, atypical and purported antipsychotic compounds were assessed as antagonists of DOI-induced behaviors in rats. 3. DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride) is an hallucinogen having high affinity and selectivity as an agonist at 5-HT2A/2C receptors. Over a 30-min period after injection, DOI (0.3-10.0 mg/kg; i.p.) produced dose-related behavioral effects including head-and-body shakes, forepaw tapping and skin-jerks. Effects of the antipsychotic drugs and other compounds (30 min pretreatment; i.p.) were examined against a fixed dose of DOI (3.0 mg/kg). 4. In a dose-dependent manner, M100907 (MDL 100,907), risperidone, haloperidol, clozapine, iloperidone, olanzapine, amperozide, remoxipride, ritanserin and the neurotensin agonist NT1 (N alpha MeArg-Lys-Pro-Trp-Tle-Leu) antagonized each of the three behavioral effects of DOI. Drugs attenuating the head-and-body shakes were equally effective in blocking both forepaw tapping and skin-jerks indicating that these behaviors are mediated by similar mechanisms. The following compounds had either inconsistent or no effect on the DOI-induced behaviors: SB 200646A, citalopram, imipramine, fluoxetine, morphine, CP 99994, diazepam, ondansetron and SKF 97541. 5. The data show that antipsychotic agents, as a drug class, effectively block the effects of DOI. These actions are selective, as a series of nine non-antipsychotic and centrally-acting drugs were generally inactive in the procedure.
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PMID:Selectivity of action of typical and atypical anti-psychotic drugs as antagonists of the behavioral effects of 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI). 1037 35

Exposure of food proteins to certain processing conditions induces two major chemical changes: racemization of all L-amino acids to D-isomers and concurrent formation of cross-linked amino acids such as lysinoalanine. Racemization of L-amino acids residues to their D-isomers in food and other proteins is pH-, time-, and temperature-dependent. Although racemization rates of the 18 different L-amino acid residues in a protein vary, the relative rates in different proteins are similar. The diet contains both processing-induced and naturally formed D-amino acids. The latter include those found in microorganisms, plants, and marine invertebrates. Racemization impairs digestibility and nutritional quality. The nutritional utilization of different D-amino acids varies widely in animals and humans. In addition, some D-amino acids may be both beneficial and deleterious. Thus, although D-phenylalanine in an all-amino-acid diet is utilized as a nutritional source of L-phenylalanine, high concentrations of D-tyrosine in such diets inhibit the growth of mice. Both D-serine and lysinoalanine induce histological changes in the rat kidney. The wide variation in the utilization of D-amino acids is illustrated by the fact that whereas D-methionine is largely utilized as a nutritional source of the L-isomer, D-lysine is totally devoid of any nutritional value. Similarly, although L-cysteine has a sparing effect on L-methionine when fed to mice, D-cysteine does not. Because D-amino acids are consumed by animals and humans as part of their normal diets, a need exists to develop a better understanding of their roles in nutrition, food safety, microbiology, physiology, and medicine. To contribute to this effort, this multidiscipline-oriented overview surveys our present knowledge of the chemistry, nutrition, safety, microbiology, and pharmacology of D-amino acids. Also covered are the origin and distribution of D-amino acids in the food chain and in body fluids and tissues and recommendations for future research in each of these areas. Understanding of the integrated, beneficial effects of D-amino acids against cancer, schizophrenia, and infection, and overlapping aspects of the formation, occurrence, and biological functions of D-amino should lead to better foods and improved human health.
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PMID:Chemistry, nutrition, and microbiology of D-amino acids. 1055 72

Recently a new variant of Creutzfeldt-Jakob disease, a human prion disease, with prominent psychiatric manifestations in the early stage was identified, suggesting that human prion disease may be associated with mental disorders. Furthermore, a novel missense mutation with asparagine-to-serine substitution at codon 171 of the human prion gene (N171S) was identified in a family with severe psychiatric symptoms. This finding provides further clue that the prion gene may be a susceptibility gene for certain psychiatric disorders. We systematically sequenced the protein-coding and untranslated exons of prion gene in 62 Han Chinese schizophrenic patients with positive family history from Taiwan. We identified two polymorphisms that alter amino acid sequences, a methionine/valine at codon 129 (M129V) and a glutamate/lysine at codon 219 (E219K), respectively. Further comparison of the genotype, allele and haplotype frequency distributions of these two polymorphisms between 234 schizophrenic patients and 100 non-psychotic controls, however, did not reveal significant differences between two groups. Besides, no other mutations in the prion gene were identified in these 62 patients. Hence, our results suggest that the prion gene may not play a major role in conferring susceptibility to schizophrenia.
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PMID:Lack of evidence to support the association of the human prion gene with schizophrenia. 1124 88


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