Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin B(12) deficiency is a common problem in elderly subjects. If a serum cobalamin level of about 150 pmol/L (200 pg/mL) is considered normal, 10-15% of the elderly are deficient. Today, however, a threshold of 220-258 pmol/L (300-350 pg/mL) is recognized as desirable in the elderly, or else sensitive markers like the blood concentration of homocysteine or methylmalonic acid (MMA) are used. Then the prevalence of cobalamin deficiency rises to up to 43%. In the elderly, this high prevalence of poor cobalamin status is predominantly caused by atrophic gastritis type B. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal absorption of the cobalamin protein complexes from food. About 20-50% of the elderly are affected. Furthermore, the reduced acid secretion leads to an alkalinization of the small intestine, which may result in bacterial overgrowth and thus to a further decrease of the bioavailability of the vitamin. In addition, some drugs such as proton pump inhibitors or H2 receptor antagonists inhibit the intestinal absorption of vitamin B(12). An already moderately reduced vitamin B(12) level is associated with vascular disease and neurocognitive disorders such as depression and impaired cognitive performance. Furthermore, a poor vitamin B(12) status is assumed to be involved in the development and progression of dementia (e.g., Alzheimer's dementia). This is especially observable if the folic acid status is reduced as well. Due to the insecure supply, the cobalamin status of elderly persons (>/=60 years) should be regularly controlled and a general supplementation with vitamin B(12) (>50 microg/day) should be considered.
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PMID:Cobalamin: a critical vitamin in the elderly. 1553 65

Homocysteine (Hcy) is harmful to neurons and blood vessels, including the cerebral microvasculature. It is possible that such effects contribute to the cascade of events that leads to cognitive decline, dementia, and depression in later life. Hcy is produced during the metabolism of the essential amino-acid methionine, which also involves a methyl group transfer derived from folate and choline metabolism. Its plasma level can be influenced by factors such as age, vitamin deficiency, renal function, and a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, where cytosine is replaced by thymidine (C-->T) at nucleotide position 677. Subjects with the TT genotype have higher homocysteine levels and may be particularly prone to experiencing depression as a result of high plasma Hcy and dysfunction of methylation metabolic pathways critical to the synthesis of noradrenaline and serotonin. We designed the present study to investigate whether older women with the TT genotype would have higher depression and lower cognitive scores than women with CT and CC genotypes. A total of 240 community-dwelling women aged 70 years or over volunteered to take part in the study - 29 carried the TT genotype, 113 the CT and 98 the CC genotype. The Beck Depression Inventory (BDI) score for subjects with the TT genotype was statistically similar to the other groups (P = 0.609). Plasma Hcy showed a modest and significant correlation with BDI scores (r = 0.21) that was independent from age, B12 and folate levels. There was no association between beck anxiety inventory (BAI) scores and MTHFR genotype or homocysteine levels. The cognitive assessment of participants included measures of verbal memory, memory for faces, verbal fluency, visuo-spatial abilities and the cognitive section of the Cambridge Examination For Mental Disorders Of The Elderly (CAMCOG)-MTHFR genotype had no clear association with cognitive scores. These results indicate that, in isolation, the MTHFR C677T gene variation does not play an important role in the modulation of mood and cognitive performance in later life.
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PMID:Contribution of the MTHFR gene to the causal pathway for depression, anxiety and cognitive impairment in later life. 1558 52

We review the findings in major depression of a low plasma and particularly red cell folate, but also of low vitamin B12 status. Both low folate and low vitamin B12 status have been found in studies of depressive patients, and an association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. It is interesting to note that Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are furthermore linked to a poor response to antidepressants, and treatment with folic acid is shown to improve response to antidepressants. A recent study also suggests that high vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is now substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is shown to be overrepresented among depressive patients, which strengthens the association. On the basis of current data, we suggest that oral doses of both folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression.
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PMID:Treatment of depression: time to consider folic acid and vitamin B12. 1567 Nov 30

Until relatively recently, depression has been considered a purely "mental" disorder and therefore in the natural domain of psychologists and psychiatrists. However, recent epidemiological studies have revealed that aging, physical and psychological stress, chronic pain, several metabolic disorders such as insulin resistance and established diabetes, alcoholism, inflammatory conditions, and vascular disorders such as arterial hypertension all may be associated with depression. The present review examines some of these depression-associated factors and the mechanisms by which they might give rise to vascular disorders such as atherosclerosis, microcirculation endothelial dysfunction, and interstitial disturbances leading to organ damage. A number of disorders involving the circulation can lead progressively and insidiously to large artery rigidity, remodeling of peripheral arteries, and alterations of the microcirculation of large blood vessels. Perturbations in vasa vasorum blood flow may contribute to atherogenesis, in addition to the influence of numerous cellular events involved in inflammation (tumor necrosis factor alpha, interleukin 1 beta, etc). Since Hans Selye first described the neuroendocrine cascade generated by experimentally induced stress half a century ago, phenomena such as the axonal release of neurotransmitters (including serotonin), accumulation of metabolites such as homocysteine, platelet-activating factor, and nitric oxide also have been implicated in the pathogenesis of depression. Moreover, vascular consequences of depression such as heart rate and pulse pressure variations may lead to endothelial dysfunction in critical microcirculation networks (cerebral, myocardial, and renal) and initiate physicochemical alterations in interstitial compartments adjacent to vital organs. The appropriate use of ambulatory monitoring of vascular parameters, such as heart rate and pulse pressure, and eventually, early identification of genetic and metabolic markers may prove helpful in the early detection of events preceding and predicting the clinical manifestations of depression.
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PMID:Depression and cardiovascular disease: a reciprocal relationship. 1587 13

The objective of the present study was to examine the relationship between serum folate, vitamin B12, and homocysteine levels and the timing of clinical improvement to fluoxetine in major depressive disorder (MDD) patients. A total of 110 outpatients with MDD who responded to an 8-wk trial of fluoxetine had serum folate, B12, and homocysteine measurements at baseline (prior to fluoxetine initiation). Onset of clinical improvement was defined as a 30% decrease in Hamilton Depression Scale scores that led to a 50% decrease by week 8. Patients with low folate levels (<or=2.5 ng/ml) were more likely to experience a later onset of clinical improvement than eufolatemic patients ( p =0.0028). B12 and homocysteine level status did not predict time to clinical improvement ( p >0.05). In conclusion, low serum folate levels were found to be associated with a delayed onset of clinical improvement during treatment with fluoxetine in MDD by, on average, 1.5 wk.
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PMID:The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine. 1587 35

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

In the recent years, elevated homocysteine plasma levels have been reported to represent a risk factor not only for atherosclerosis, but also to be associated with dementia, depression and-in a gender-specific manner-schizophrenia. Here, we explored a possible association between homocysteinemia and psychiatric disorders. Fasting homocysteine, vitamin B12 and folate were determined in an ethnically homogeneous female population with different psychiatric disorders. Homocysteine was not elevated in females suffering from schizophrenia (mean, 11.6+/-5.8 micromol/l). As shown previously, increased homocysteine concentrations were associated not only with dementia of different aetiology (mean, 17.2+/-6.7 micromol/l; chi2=23.39, p<0.001, compared to the schizophrenia group), but also with depressive disorders (mean, 12.9+/-3.8 micromol/l; chi2=6.88, p=0.009). B12 and folate levels did not differ between different diagnostic groups. To further explore the connection between homocysteinemia and affective psychoses, a case-control study examining the C677T and the A1298C variants of methylenetetrahydrofolate reductase was conducted. The latter polymorphism not only was associated with affective psychoses in general, but also when divided in unipolar depression and bipolar affective disorder. In conclusion, we suggest that in females homocysteinemia is an unspecific risk factor for organic brain disorders like dementia, and possibly depression, but not for schizophrenia.
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PMID:Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses. 1605 53

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

Low dietary folate intake has been implicated as a risk factor for depression. However, observational epidemiological studies are plagued by problems of confounding, reverse causality and measurement error. A common polymorphism (C677T) in MTHFR is associated with methyltetrahydrofolate reductase (MTHFR) activity and circulating folate and homocysteine levels and offers insights into whether the association between low folate and depression is causal. We genotyped this polymorphism in 3,478 women in the British Women's Heart and Health Study. In these women, we looked at the association between genotype and three indicators of depression; ever diagnosed as depressed, currently taking antidepressants and the EuroQol mood question. We also carried out a systematic review and meta-analysis of all published studies which have looked at the association between MTHFR C677T genotype and depression. In the British Women's Heart and Health Study, we found evidence of an increased risk of ever being diagnosed as depressed in MTHFR C677T TT individuals compared with CC individuals, odds ratio (OR) 1.35(95% CI: 1.01, 1.80). Furthermore, we identified eight other studies, which have examined the association between depression and MTHFR C677T. We were able to include all of these studies in our meta-analysis together with our results, obtaining an overall summary OR of 1.36 (95% CI: 1.11, 1.67, P=0.003). Since this genotype influences the functioning of the folate metabolic pathway, these findings suggest that folate or its derivatives may be causally related to risk of depression.
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PMID:The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis. 1804 12


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