Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

Folate and vitamin B12 are required both in the methylation of homocysteine to methionine and in the synthesis of S-adenosylmethionine. S-adenosylmethionine is involved in numerous methylation reactions involving proteins, phospholipids, DNA, and neurotransmitter metabolism. Both folate and vitamin B12 deficiency may cause similar neurologic and psychiatric disturbances including depression, dementia, and a demyelinating myelopathy. A current theory proposes that a defect in methylation processes is central to the biochemical basis of the neuropsychiatry of these vitamin deficiencies. Folate deficiency may specifically affect central monoamine metabolism and aggravate depressive disorders. In addition, the neurotoxic effects of homocysteine may also play a role in the neurologic and psychiatric disturbances that are associated with folate and vitamin B12 deficiency.
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PMID:Folate, vitamin B12, and neuropsychiatric disorders. 915 10

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

Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infancy. We have previously shown that the TPN solution is directly toxic to the liver, and that this toxicity appears to be mediated by one or more amino acids. Elevated serum methionine levels, without corresponding increases in its metabolites, suggest that accumulation of this toxic amino acid may cause TPN cholestasis. Nine-week-old rabbits (n = 28) were divided into three groups. The FED group was fed standard rabbit chow ad libitum. The TPN group was not fed and received only i.v. TPN (including methionine 121 mg.kg-1.d-1), and lipids. The EXP group was fed chow ad libitum and received i.v. methionine (121 mg.kg-1.d-1). After 14 d, we evaluated bile flow, bromosulfophthalein excretion, serum liver enzymes, liver histology, and serum amino acid levels. Bile flow was significantly depressed in the TPN and EXP groups compared with FED controls (32.9 +/- 9.4 and 45.7 +/- 14.4 versus 82.9 +/- 13.8). Excretion of the bilirubin analog bromosulfophthalein tended to be delayed by methionine infusion (p = 0.15). Serum liver enzymes (aspartate transaminase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase) were normal in all groups. Histologic liver injury in the EXP group was similar to that caused by TPN. Balloon degeneration, and portal inflammation were seen in both groups. Homocysteine, an early metabolite of methionine, was elevated in the TPN and EXP groups compared with FED controls. Intravenous methionine is hepatotoxic. Despite full oral feeding, it produces a depression of bile flow and histologic liver injury similar to that seen with TPN. Elevated homocysteine levels suggests an enzymatic block early in the pathway of methionine metabolism. We believe that methionine may be an important factor in the pathogenesis of TPN cholestasis.
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PMID:Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. 1023 61

Depolarization-induced suppression of inhibition (DSI) is a process whereby brief approximately 1-s depolarization to the postsynaptic membrane of hippocampal CA1 pyramidal cells results in a transient suppression of GABA(A)ergic synaptic transmission. DSI is triggered by a postsynaptic rise in [Ca(2+)](in) and yet is expressed presynaptically, which implies that a retrograde signal is involved. Recent evidence based on synthetic metabotropic glutamate receptor (mGluR) agonists and antagonists suggested that group I mGluRs take part in the expression of DSI and raised the possibility that glutamate or a glutamate-like substance is the retrograde messenger in hippocampal CA1. This hypothesis was tested, and it was found that the endogenous amino acids L-glutamate (L-Glu) and L-cysteine sulfinic acid (L-CSA) suppressed GABA(A)-receptor-mediated inhibitory postsynaptic currents (IPSCs) and occluded DSI, whereas L-homocysteic acid (L-HCA) and L-homocysteine sulfinic acid (L-HCSA) did not. Activation of metabotropic kainate receptors with kainic acid (KA) reduced IPSCs; however, DSI was not occluded. When iontophoretically applied, both L-Glu and L-CSA produced a transient IPSC suppression similar in magnitude and time course to that observed during DSI. Both DSI and the actions of the amino acids were antagonized by (S)-alpha-methyl-4-carboxyphenylglycine ([S]-MCPG), indicating that the effects of the endogenous agonists were produced through activation of mGluRs. Blocking excitatory amino acid transport significantly increased DSI and the suppression produced by L-Glu or L-CSA without affecting the time constant of recovery from the suppression. Similar to DSI, IPSC suppression by L-Glu or L-CSA was blocked by N-ethylmaleimide (NEM). Moreover, paired-pulse depression (PPD), which is unaltered during DSI, is also not significantly affected by the amino acids. Taken together, these results support the glutamate hypothesis of DSI and argue that L-Glu or L-CSA are potential retrograde messengers in CA1.
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PMID:Evidence for endogenous excitatory amino acids as mediators in DSI of GABA(A)ergic transmission in hippocampal CA1. 1056 26

Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival.
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PMID:High-dose pyridoxine as an 'anti-stress' strategy. 1085 91

Depression is associated with elevated rates of cardiovascular morbidity and mortality. This elevation seems to be due to a significantly increased risk of coronary artery disease and myocardial infarction and, once the ischemic heart disease is established, sudden cardiac death. Recent data suggest that the increased rates of cardiovascular disease in patients with depression may be the result of one or more still-unrecognized underlying physiological factors that predispose a patient to both depression and cardiovascular disease. Two possibly related factors that may have a causal relation with both depressive disorders and cardiovascular disease are an omega-3 fatty acid deficiency and elevated homocysteine levels. We present the available data connecting cardiovascular disease, depression, omega-3 fatty acids, and homocysteine. In addition, we suggest research strategies and some preliminary treatment recommendations that may reduce the increased risk of cardiovascular mortality in patients with major depressive disorder.
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PMID:Omega-3 fatty acids, homocysteine, and the increased risk of cardiovascular mortality in major depressive disorder. 1160 Apr 87

Because the role of elemental sulfur in human nutrition has not been studied extensively, it is the purpose of this article to emphasize the importance of this element in humans and discuss the therapeutic applications of sulfur compounds in medicine. Sulfur is the sixth most abundant macromineral in breast milk and the third most abundant mineral based on percentage of total body weight. The sulfur-containing amino acids (SAAs) are methionine, cysteine, cystine, homocysteine, homocystine, and taurine. Dietary SAA analysis and protein supplementation may be indicated for vegan athletes, children, or patients with HIV, because of an increased risk for SAA deficiency in these groups. Methylsulfonylmethane (MSM), a volatile component in the sulfur cycle, is another source of sulfur found in the human diet. Increases in serum sulfate may explain some of the therapeutic effects of MSM, DMSO, and glucosamine sulfate. Organic sulfur, as SAAs, can be used to increase synthesis of S-adenosylmethionine (SAMe), glutathione (GSH), taurine, and N-acetylcysteine (NAC). MSM may be effective for the treatment of allergy, pain syndromes, athletic injuries, and bladder disorders. Other sulfur compounds such as SAMe, dimethylsulfoxide (DMSO), taurine, glucosamine or chondroitin sulfate, and reduced glutathione may also have clinical applications in the treatment of a number of conditions such as depression, fibromyalgia, arthritis, interstitial cystitis, athletic injuries, congestive heart failure, diabetes, cancer, and AIDS. Dosages, mechanisms of action, and rationales for use are discussed. The low toxicological profiles of these sulfur compounds, combined with promising therapeutic effects, warrant continued human clinical trails.
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PMID:Sulfur in human nutrition and applications in medicine. 1189 44

The study of different neurological problems, including stroke, Alzheimer's disease (AD), and depression, has propelled a greater interest in interrelationships among folate, homocysteine, and neurological function. Specifically, low folate status is a suspected risk factor for depression that also results in an increase in circulating levels of the sulfur amino acid homocysteine. Homocysteine has emerged as an independent risk factor for stroke, and recent studies suggest that vascular disease affecting the brain and Alzheimer's disease may result together in senile dementia. The relationship between stroke and AD was at first interpreted as coincidence, given the pathologic distinctions between the two diseases. However, the connection is now hypothesized to reflect some common pathogenic factors involving folate, homocysteine, or both. It remains unclear whether there is a causal relationship between neurological dysfunction in either condition with folate or homocysteine. Nevertheless, since improvement of folate status lowers homocysteine levels, the hypothesis that folate supplementation may lower the risk of several important health consequences of aging, including various forms of neuropsychiatric dysfunction, is worthy of current intensive exploration.
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PMID:Folate, homocysteine, and neurological function. 1213 67

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


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