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)

Homocysteine is a sulfur containing amino acid that has been widely investigated for its putative role in cardiovascular and neuropsychiatric disorders. It has been suggested that homocysteine has implications especially in young, male schizophrenia patients. In this prospective case-control study, we compared plasma homocysteine levels in a group of adolescent schizophrenia inpatients (aged 14-21 years; n=23) to normal healthy controls (n=51). Mean plasma homocysteine levels were significantly higher in the patient group than in the control group (15.40+/-2.00 and 9.78+/-0.33 micromol/L, respectively, p<0.032). The difference was almost entirely attributable to the male schizophrenia subgroup (18.18+/-5.65 in male patients vs. 10.31+/-5.33 micromol/L in female patients). The group x sex interaction was statistically significant (p=0.0035). These data indicate that a subgroup of male adolescent schizophrenia patients has high homocysteine blood levels. The role of homocysteine in the pathophysiology of adolescent-onset schizophrenia merits further investigation.
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PMID:Homocysteine levels in adolescent schizophrenia patients. 1664 49

European researchers have observed that schizophrenia is 3 times more frequent in immigrants than in native-born subjects. This increased risk is even higher in dark-skinned immigrants, and the second generation is more affected than the first one. Immigrant status is an important environmental risk factor not only for schizophrenia but also for other psychoses. The explanations proposed to date have been mainly related to epidemiological biases and psychological reasons, such as racism or social defeat, but no biological hypotheses have been tested so far. This article proposes two biological hypotheses related to changes in sun exposure, changes in diet, and stress associated with immigration, which would explain the increased risk for psychosis associated with immigrant status. (1) Vitamin D insufficiency has been proposed as a risk factor for schizophrenia. The main source of vitamin D is through photosynthesis by sun exposure, and dark skins need more sun exposure to maintain adequate blood levels. Vitamin D insufficiency in adulthood could explain why dark-skinned immigrants develop psychosis when moving to high latitude countries, and its insufficiency during pregnancy could explain why the observed risk is higher in the second generation. (2) The second hypothesis is that of epigenetics, with psychosis resulting from modifications in gene expression caused by changes in diet and/or stress related to immigration. The role of homocysteine and the vitamin B-complex, especially folic acid, in these changes in DNA transcription would vary according to the polymorphism of the methylenetetrahydrofolate reductase gene. The vitamin D insufficiency and epigenetics hypotheses are consistent with yet unexplained findings well known in the epidemiology of schizophrenia, such as the increased risk in the urban environment, the excess of winter births, the excess of schizophrenia births after maternal famine, and the shorter interbirth period before a schizophrenia birth. In order to test these hypotheses, epidemiological studies of psychosis and immigration should include objective measures of skin color, which is predicted to be a more important risk factor than ethnicity. They should measure vitamin D, homocysteine and vitamin B-complex status and assess the polymorphisms of the vitamin D receptors and the methylenetetrahydrofolate reductase gene. If confirmed, these hypotheses would lead to effective and inexpensive preventive measures which would markedly decrease the rates of psychosis and schizophrenia, as well as the burden and stigma of these diseases, and greatly improve the mental health of immigrants.
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PMID:Why are immigrants at increased risk for psychosis? Vitamin D insufficiency, epigenetic mechanisms, or both? 1751 23

Homocysteine levels are affected by diet factors such as vitamin deficiencies, non-diet factors such as genetic disorders, and stress exposure. Hyperhomocysteinemia has been implicated in several disorders, including cardiovascular disease, depression, schizophrenia, Alzheimer's and Parkinson's disease. Since sex differences play a role both in stress responses and in susceptibility to various diseases, the objective of this study was to evaluate possible alterations in homocysteine metabolism including cysteine, folate, and vitamin B(6), and oxidative stress markers in female rats exposed to different types of acute stress. Female rats were randomly distributed into eight groups according to stress manipulation (restraint, swimming, cold and control) and estrous cycle (diestrus and estrus). In general no significant differences were seen between rats in estrus and diestrus. Restraint stress was the only type of stress that altered homocysteine concentrations (+33% relative to controls). An increase in levels of thiobarbituric acid reactive substances (TBARS) and a decrease in total glutathione (GSHt) concentration were also observed in animals subjected to restraint and swimming stress, suggesting the possibility of oxidative damage. Thus, both the homocysteine results and the oxidative stress data indicated that restraint stress was the most powerful stress manipulation in female rats, as previously observed in male rats. These findings indicate that hormonal and gonadal differences do not interfere with stress responses related to homocysteine metabolism and suggest that putative gender-related differences in homocysteine responses are probably not involved in the differential prevalence of some diseases in human males and females.
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PMID:Acute stressor-selective effects on homocysteine metabolism and oxidative stress parameters in female rats. 1705 2

Elevated plasma levels of the amino acid homocysteine have been associated with schizophrenia, particularly in young male patients. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. In order to investigate this association, we determined plasma homocysteine, folate and B12 levels in 97 (67 males and 30 females) inpatients with chronic schizophrenia and 103 (46 males and 57 females) controls. Patients and controls did not differ in folate or B12 levels, after adjusting for age. Patients with schizophrenia had higher plasma homocysteine than controls (mean=15.42 micromol/l in cases versus 11.54 micromol/l in controls: F(1,195)=17.978; p<0.001). This difference persisted after controlling for folate and B12 concentrations. Both male and female patients had increased plasma homocysteine compared to controls [(males: mean=16.61 micromol/l in cases versus mean=13.72 in controls: F(1,110)=5.54; p=0.020) (females: mean=12.78 micromol/l in cases versus mean=9.79 micromol/l in controls: F(1,84)=13.54; p<0.001)]. When dividing our sample into two age groups (age < and > or =50 years), both young and older females and younger males with schizophrenia had increased plasma homocysteine compared to controls. We therefore suggest that homocysteinemia is a general risk factor for schizophrenia. We further suggest that it is not limited to young male patients and is not necessarily associated with low folate or B12 levels.
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PMID:Plasma homocysteine, folate and B12 in chronic schizophrenia. 1759 77

Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin - called as polypill - was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites and other products prevent platelet aggregation, lower blood pressure, reduce LDL-C, and ameliorate the adverse actions of homocysteine. Thus, EFAs and their metabolites show all the actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules, have no significant side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and children; and have been shown to reduce the incidence cardiovascular diseases. I propose that a rational combination of omega-3 and omega-6 fatty acids is as beneficial as that of the "polypill"; and may even show additional benefit in the prevention of depression, schizophrenia, Alzheimer's disease, and enhance cognitive function.
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PMID:Do polyunsaturated fatty acids behave like an endogenous "polypill"? 1762 83

The aim of the present study was to investigate serum paraoxonase/arylesterase activities and oxidation/oxidizability of apolipoprotein B-containing lipoproteins and several coronary artery disease risk factors, including homocysteine, high sensitive C-reactive protein, tumour necrosis factor-alpha, leptin and adiponectin in patients with schizophrenia. Oxidation of lipoproteins plays an important role in atherogenesis, and the enzyme paraoxonase has been shown to prevent lipoprotein oxidation. Furthermore, low paraoxonase activity has been suggested to predict coronary artery disease. Forty patients who fully met the fourth Diagnostic and Statistical Manual of Mental Disorders criteria for schizophrenia and 35 healthy control subjects were included in the study. Serum paraoxonase/arylesterase activities were determined spectrophotometrically. Malondialdehyde levels of apolipoprotein B-containing lipoproteins were determined before and after incubation with copper-sulphate, which yielded basal- and Delta-malondialdehyde values, respectively. Homocysteine and highly sensitive C-reactive protein levels were determined using a fluorescence-polarization immunoassay and immunonephelometry, respectively. Leptin and adiponectin levels were measured with radioimmunoassay and tumour necrosis factor-alpha was determined by enzyme linked immunosorbent assay. Serum paraoxonase and arylesterase activities were significantly lower and Delta-malondialdehyde levels were significantly higher in the schizophrenia group compared with the control group. However, there were not any significant differences in other parameters of the study between the study groups. There was a significant increase in body mass index and serum triglyceride and very low density lipoprotein cholesterol levels in the schizophrenic group after 6 weeks of treatment. These parameters were significantly increased in patients treated with atypical antipsychotics but not in patients treated with typic or long acting antipsychotics. The results of the present study suggest that patients with schizophrenia might have increased risk for coronary artery disease related to reduced serum paraoxonase activity and increased oxidizability of apolipoprotein B-containing lipoproteins.
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PMID:Coronary artery disease risk factors in patients with schizophrenia: effects of short term antipsychotic treatment. 1771 3

Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phosphatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B(6)) synthesis. PLP is a metabolically-active form of vitamin B(6) and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P<0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population.
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PMID:Association between PNPO and schizophrenia in the Japanese population. 1785 Oct 41

It has been suggested that an elevated serum or plasma homocysteine level may be a risk factor for neuropsychiatric conditions such as Alzheimer's disease, schizophrenia, and depression. Because depression is closely related to anxiety disorders, and because it has been suggested that stress may be associated with an elevated homocysteine level, we studied whether serum homocysteine levels are elevated in patients with posttraumatic stress disorder (PTSD). Total serum homocysteine levels in 28 male patients with PTSD were compared to those of 223 healthy controls. The effect of PTSD on the serum homocysteine level was significant (F=42.96, P<.0001). In a regression model for the PTSD patients, the duration of PTSD was found to predict serum homocysteine levels (t=2.228, P=.035). Our results suggest that elevated levels of homocysteine in male patients with PTSD may be related to pathophysiological aspects associated with the chronicity of this disorder.
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PMID:Elevated serum homocysteine levels in male patients with PTSD. 1799 87

A disturbed methylation has been proposed as a mechanism via which homocysteine is associated with diseases like vascular disease, neural tube defects and mental disorders. Catechol-O-methyltransferase (COMT) is involved in the S-adenosylmethionine-dependent methylation of catecholamines and catecholestrogens and in this way contributes to homocysteine synthesis. COMT dysfunction has been related to schizophrenia and breast cancer. We hypothesized that COMT dysfunction by virtue of functional genetic polymorphisms may affect plasma total homocysteine (tHcy). Our primary objective was to study the association between common COMT polymorphisms and tHcy. Secondly, we evaluated these polymorphisms as a risk factor for recurrent venous thrombosis. We obtained genotype data from four polymorphisms in the COMT gene (rs2097603, rs4633, rs4680 [324G>A] and rs174699) from 401 population-based controls. We performed haplotype analysis to investigate the association between common haplotypes and tHcy. In addition, we assessed the rs4680 variant as a genetic risk factor in a case-control study on recurrent venous thrombosis (n = 169). We identified a common haplotype that was significantly associated with tHcy levels. This effect was largely explained by the rs4680 variant, resulting in an increase in tHcy of 10.4% (95% CI 0.01 to 0.21, p = 0.03) for 324AA compared with 324GG subjects. Interestingly, we found that the 324AA genotype was more common in venous thrombosis patients (OR 1.61 [95% CI 0.97 to 2.65], p = 0.06) compared to control subjects. We show that the COMT rs4680 variant modulates tHcy, and might be associated with venous thrombosis risk as well.
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PMID:Catechol-O-methyltransferase genotype is associated with plasma total homocysteine levels and may increase venous thrombosis risk. 1806 18

Meta-analysis recently suggested that a 5 muM increase in homocysteine is associated with a 70% higher risk for schizophrenia. Elevated homocysteine is reported to alter macromolecule methylation. We studied whether elevated plasma homocysteine levels in schizophrenia are associated with altered leukocyte global DNA methylation. DNA was extracted from peripheral blood leukocytes of 28 schizophrenia patients vs. 26 matched healthy controls. Percent of global genome DNA methylation was measured using the cytosine-extension method. Homocysteine levels were higher in schizophrenia patients than in controls. No difference in global DNA methylation between schizophrenia patients and control subjects was found (74.0%+/-14.8 vs. 69.4+/-22.0, p=0.31). A significant interaction between diagnosis and smoking on DNA methylation was obtained (F=6.8, df=1,47, p=0.032). Although leukocytes may be a useful cell model to evaluate epigenetic changes such as global DNA methylation in brain, future studies should compare global DNA methylation in peripheral tissue vs. brain in laboratory animals.
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PMID:No association between global leukocyte DNA methylation and homocysteine levels in schizophrenia patients. 1827 18


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