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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a large family with hyperhomocysteinemia, the first to be reported in Poland. The proband's coronary complaints appeared at the age of 20, and by the age of 50 he had suffered extensive myocardial infarction. Examination of 17 persons from 4 generations revealed hyperhomocysteinemia in 2 daughters of the proband, while more discrete abnormalities were detected during methionine loading test in two other persons. Levels of cystathionone beta-syntetase and methyleno-FH4 reductase were normal in skin fibroblast culture. Treatment with folic acid and vitamin B12 led to 5-fold depression of plasma homocysteine in the proband, and complete normalization in the other treated member of the family.
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PMID:[Familial hyperhomocysteinemia with early development of atherosclerosis]. 908 46

Homocysteine (Hcy) may represent a metabolic link in the pathogenesis of atherosclerotic vascular diseases and old-age dementias. Hyperhomocysteinemia is an independent risk factor for coronary artery disease and peripheral vascular disease, and is also associated with cerebrovascular disease; specifically, the risk of extracranial carotid atherosclerosis significantly increases in relation to Hcy levels. Hcy is a reliable marker of vitamin B12 deficiency, a common condition in the elderly which is known to induce neurological deficits including cognitive impairment; a high prevalence of folate deficiency has been reported in psychogeriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAMe), a major methyl donor in CNS; therefore, deficiencies in either of these vitamins lead to a decrease in SAMe and increase in Hcy, which can be critical in the aging brain. Another pathogenetic mechanism linking high Hcy levels to reduced cognitive performances in the elderly might be represented by excitotoxicity, since hyperhomocysteinemia may lead to an excessive production of homocysteic acid and cysteine sulphinic acid, which act as endogenous agonists of NMDA receptors. Considering the reasonably high prevalence in the general population of a genetic predisposition to a thermolabile form of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), hyperhomocysteinemia can be seen as the result of multiple genetic and environmental factors leading to vascular and/or neurodegenerative disorders where age-related involutive phenomena represent a common pathogenetic ground. Systematic studies in different psychogeriatric conditions monitoring Hcy levels and clinical features before and after vitamin supplementation are therefore highly recommended.
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PMID:Role of homocysteine in age-related vascular and non-vascular diseases. 935 35

Hyperhomocysteinemia (HHCY) is a consequence of disturbed methionine metabolism. It results from enzyme and/or vitamin deficiency. Epidemiological and clinical studies have proven HHCY to be an independent risk factor for atherosclerotic cardiovascular diseases, stroke, peripheral arterial occlusive disease and venous thrombosis. Trials in progress may clarify the "causality" of high homocysteine (HCY) concentrations and will assess the value of HCY lowering therapy. HHCY is also seen as a risk factor for neurodegenerative diseases such as cognitive impairment, dementia, Alzheimer's disease, and also for depression. There is a high prevalence of HHCY as a syndrome of vitamin shortage in elderly subjects, which strongly increases with advancing age. Elderly people have a high frequency of vitamin B12 deficiency which is more reliably diagnosed by measurement of serum methylmalonic acid and holotranscobalamin II, the metabolically active B12 fraction, than by total serum vitamin B12. Subjects who follow a strict vegetarian diet also have a high prevalence of HHCY caused by vitamin B12 deficiency. For prevention of neurological damages an early diagnosis of vitamin B12 deficiency is important. Furthermore, HHCY is a factor in the pathogenesis of neural tube defects and preeclampsia. HCY should be measured in patients with a history of atherothrombotic vessel diseases, in patients with diabetes or hyperlipidemia, in renal patients, in adipose subjects, in elderly people, in vegetarians, in postmenopausal women, and in early pregnancy.
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PMID:Hyperhomocysteinemia: a new risk factor for degenerative diseases. 1238 6

The author presents an overview of the current literature on homocysteine as a risk factor for neuropsychiatric disorders. The databases MEDLINE, Current Contents and EMBASE were searched (between 1966 and 2002) for English language publications with the key words 'Homocysteine' and 'Stroke'; 'Alzheimer Disease'; 'Cognitive Impairment'; 'Epilepsy'; 'Depression'; or 'Parkinson's disease'. Individual articles were hand searched for relevant cross-references. It is biologically plausible that high homocysteine levels may cause brain injury and neuropsychiatric disorders. Homocysteine is proatherogenic and prothrombotic, thereby increasing the risk of cerebrovascular disease, and may have a direct neurotoxic effect. Evidence for homocysteine as a risk factor for cerebral microvascular disease is conflicting but warrants further study. Cross-sectional and some longitudinal studies support increased prevalence of stroke and vascular dementia in hyperhomocysteinemic individuals. The evidence of increased neurodegeneration is accumulating. The relationship with depression is still tentative, as it is with epilepsy. Currently, treatment studies are necessary to place the evidence on a stronger footing, and maybe high-risk patients should be screened for hyperhomocysteinemia and this should be treated with folic acid. More research evidence is necessary before population screening can be recommended.
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PMID:[Homocysteine and neuropsychiatric disorders]. 1505 41

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.
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PMID:[Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences]. 1510 81

Elevated total homocysteine (tHcy) concentrations have been found to be associated with cardiovascular disease and dementia in old age. The present study was performed to identify the prevalence of hyperhomocysteinemia (HHcy) and to analyze the association between tHcy concentration and sociodemographic characteristics, nutritional parameters, and cognitive and functional status in this sample of hospitalized geriatric patients. A total of 214 patients (77% females) 65+ years old admitted into an acute care geriatric ward of an internal medical department in the Northern Italy were studied. tHcy concentration was measured using a high-performance liquid chromatography with fluorescence detection (HPLC-F). Information about nutrition (body mass index [BMI], serum albumin, cholesterol, and transferrin) was collected on admission. Functional status was investigated with the Basic Activities of Daily Living scale (ADL) and the Instrumental Activities of Daily Living scale (IADL); cognitive and affective status were assessed by the Mini-Mental State Evaluation (MMSE) and the Geriatric Depression Scale (GDS). The mean tHcy concentration was 18.4 +/- 13.1 micromol/L; 74.2% of males and 68.9% of females had HHcy (> 12 micromol/L). Sixty-four percent of patients with normal serum vitamin B12 and folate concentrations had HHcy. Elevated tHcy concentrations were associated with older age, male gender, increasing serum creatinine, lower MMSE score, and disability. The mean tHcy concentration depended on the occurrence of different diseases. Patients affected by atherosclerotic diseases, such as ischemic heart diseases, cerebrovascular diseases, and dementia had higher mean tHcy concentration than those without diagnosed vascular diseases. In multivariate analysis, vitamin B12, folate, serum albumin, creatinine, and disability emerged as factors associated with tHcy, adjusted for age, gender, education, MMSE score, and atherosclerotic diseases. Our results suggest that the prevalence of HHcy in hospitalized patients is very high, even in subjects with normal cobalamin and folate concentrations. High Hcy concentration can be associated with functional impairment.
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PMID:Homocysteine and disability in hospitalized geriatric patients. 1528 Oct 11

Homocysteine (Hcy) is a thyol amino acid resulting from de-methylation of methionine, an essential amino acid derived from dietary proteins. It is metabolized through two pathways: re-methylation and transsulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia has been identified as a risk factor for cerebrovascular disease, dementia, impaired cognitive function and depression. Several drugs may interfere with metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. Lipid-lowering agents, used to reduce the risk of cerebral venous thrombosis or occlusive vascular disease in patients with high levels of plasmatic lipids, can increase plasma Hcy levels. Hyperhomocysteinemia has been also documented in Parkinson disease patients treated with levodopa and in epileptic patients after chronic treatment with antiepileptic drugs. In contrast, vitamins supplementations may be warranted in patients treated with lipid-lowering agents, levodopa and antiepileptic drugs in order to maintain normal plasma Hcy values. In contrast, higher doses of vitamins can induce dysfunctions in central and peripheral nervous system; therefore excessive supplements should be avoided.
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PMID:Increase in plasma homocysteine levels induced by drug treatments in neurologic patients. 1603 38

Homocysteine is a sensitive marker of folate and vitamin B12 deficiency. Numerous studies have confirmed the association between folate deficiency and depression. It is not completely understood whether homocysteine is solely a marker for folate deficiency or if it may play a more direct role in the expression of mood disorders. This review describes the biochemical, neurochemical and clinical correlations of folate deficiency and hyperhomocysteinemia in relation to depression.
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PMID:Homocysteine and folate metabolism in depression. 1610 54

Homocysteine is a sulfur-containing amino acid that is involved in one-carbon metabolism. Hyperhomocysteinemia is a common phenomenon among elderly people. There is growing evidence of an association between hyperhomocysteinemia and geriatric multisystem problems, including coronary artery disease, stroke, peripheral vascular disease, cognitive impairment, dementia, depression, osteoporotic fractures, and functional decline. The proposed mechanisms of the association include angiotoxicity, neurotoxicity, and inhibition of collagen cross-linking. A homocysteine-lowering strategy may prevent or slow the development of these age-related problems. Vitamin supplementation and folic acid fortification of grain foods have been shown to decrease plasma homocysteine concentrations. More research is needed to investigate whether lifelong homocysteine lowering can prevent the development of late-life morbidity.
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PMID:The role of homocysteine in multisystem age-related problems: a systematic review. 1618 62

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


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