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)

1. The incidence of folic acid deficiency is high in patients with various psychiatric disorders including depression, dementia and schizophrenia. 2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms. 3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels. 4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients. 5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15-20 mg/day) are known to be toxic and to cause mental symptoms. 6. Two placebo-controlled studies have demonstrated beneficial effects of folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day. 7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxytryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT. 8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency. 9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms. 10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.
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PMID:Folic acid and psychopathology. 268 87

The effect of vitamin B12 (B12) deficiency on the levels of S-adenosylmethionine (SAM) in tissues and the activities of hepatic methionine synthase, methionine adenosyltransferase and glycine N-methyltransferase were investigated. The striking depression of methionine synthase activity was observed in all rats fed the B12-deficient diets with or without methionine supplementation for 150 days. The SAM level in liver was decreased by B12 deficiency. However, brain SAM level was not affected. The activities of hepatic methionine adenosyltransferase isozymes, alpha-form and beta-form, were decreased by B12 deficiency. Hepatic glycine N-methyltransferase activity in rats fed the low methionine-B12-deficient diet showed a tendency to lower, although the change the activity was not statistically significant, compared with B12-supplemented rats. It is proposed that the fall in the activity of hepatic methionine adenosyltransferase may be one of the causes of the decreased hepatic SAM level in B12-deficient rats.
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PMID:Effect of vitamin B12 deficiency on S-adenosylmethionine metabolism in rats. 273 12

Heart sarcolemma has been shown to possess three catalytic sites (I, II and III) for methyl transferase activity (Panagia V, Ganguly PK and Dhalla NS. Biochim Biophys Acta 792:245-253, 1984). In this study we examined the effect of phosphatidylethanolamine N-methylation on ATP-independent Ca2+ binding and ATPase activities in isolated rat heart sarcolemma. Both low affinity (1.25 mM Ca2+) and high affinity (50 microM Ca2+) Ca2+ binding activities were decreased following incubation of sarcolemmal membranes with AdoMet under optimal conditions for site II and III. Similarly, Ca2+ ATPase activities measured at 1.25 mM and 4 mM Ca2+ were depressed by phospholipid N-methylation. S-adenosyl homocysteine, a specific inhibitor of phospholipid N-methylation, prevented the depression of low affinity Ca2+ binding and Ca2+ ATPase activities, whereas the methylation-induced effect on the high affinity Ca2+ binding was not influenced by this agent. Pretreatment of sarcolemma with methyl acetimidate hydrochloride, an amino group blocking agent, also prevented the methylation-induced inhibition of both Ca2+ binding and Ca2+ ATPase. A further decrease in Ca2+ binding and Ca2+ ATPase activities together with a marked increase in the intramembranal level of PC was seen when membranes were methylated under the site III conditions in the presence of phosphatidyldimethylethanolamine as exogenous substrate. There was no effect of phospholipid methylation on sarcolemmal Na+-K+ ATPase and Mg2+ ATPase activities. These results indicate a role of phospholipid N-methylation in the regulation of sarcolemmal Ca2+ ATPase and low affinity ATP-independent Ca2+ binding.
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PMID:Decreased Ca2+-binding and Ca2+-ATPase activities in heart sarcolemma upon phospholipid methylation. 284 56

The antidepressant property of S-adenosylmethionine (SAMe) has been supported by several uncontrolled and controlled studies. Compared to standard antidepressant agents, SAMe has fewer side-effects and shorter lag period. Future studies to delineate SAMe-responsive depression are warranted.
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PMID:S-adenosylmethionine in the treatment of depression. 305 Jun 30

Twenty subjects entered a double-blind placebo-controlled trial of SAM in depression. Prolactin concentrations were measured before and after 14 days' treatment. There was a highly significant fall in prolactin concentrations in the SAM-treated group.
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PMID:The influence of S-adenosylmethionine (SAM) on prolactin in depressed patients. 329 21

The effect of S-adenosylmethionine (SAMe) and placebo was evaluated in a short-term crossover study of 17 patients with primary fibromyalgia. Eleven of 17 patients had a significant depressive state as assessed by either the Hamilton Depression Rating Scale or the Scala di Autovalutazione per la Depressione (SAD) rating scale. The number of trigger points plus painful anatomic sites decreased after administration of SAMe (p less than 0.02) but not after placebo treatment. In addition, scores on both the Hamilton and SAD rating scales improved after SAMe administration (p less than 0.05 and p less than 0.005, respectively), whereas they did not significantly change after placebo treatment. In all the patients, there was a good correlation between scores on the Hamilton rating scale and the number of trigger points. Thus, this preliminary study confirms the close relationship between primary fibromyalgia and psychologic disturbances, particularly with regards to a depressive state. SAMe treatment, by improving the depressive state and reducing the number of trigger points, seems to be an effective and safe therapy in the management of primary fibromyalgia.
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PMID:Evaluation of S-adenosylmethionine in primary fibromyalgia. A double-blind crossover study. 331 38

Two independent lines of inquiry have implicated some disturbance of one-carbon cycle metabolism in affective disorders. Folic acid deficiency commonly leads to depression, and S-adenosylmethionine has been reported to have antidepressant properties. Methionine adenosyltransferase has been reported to be underactive in depression and schizophrenia and overactive in mania. This study reports the effects on erythrocyte methionine adenosyltransferase (MAT) kinetics (Vmax) of a 2-week treatment in a population of patients housed on a psychiatric research ward. The drug-free schizophrenic patients and depressives had, upon admission, low Vmax values, and the drug-free manic patients had high Vmax values on admission. After 2 weeks of appropriate treatment, the values for all three patient samples showed significant normalization (i.e., the levels rose in schizophrenics and depressives and fell in manics). We have further shown that pretreatment low levels of erythrocyte membrane phosphatidylcholine in depressives and high levels in manics show statistically significant normalization following 2 weeks of pharmacotherapy. The significance of these results is discussed.
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PMID:Abnormalities of one-carbon metabolism in psychiatric disorders: study of methionine adenosyltransferase kinetics and lipid composition of erythrocyte membranes. 379 Jun 25

S-adenosyl-methionine (SAMe) is currently undergoing trials as a possible antidepressant. Because SAMe's mechanism of action is obscure and norepinephrine (NE) is often implicated in affective disorders, we studied the effects of SAMe on this neurotransmitter in volunteers. Plasma NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the supine and standing position were studied before and after acute placebo or a single 400 mg dose of SAMe and following seven daily administrations; concomitant measures were heart rate (HR) and blood pressure. Subjects were unable to distinguish acute drug from placebo, and although chronic SAMe administration was open, they reported no behavioral effects. Standing HR and plasma NE were reduced following chronic SAMe. Qualitatively similar changes are obtained following chronic treatment with monoamine oxidase inhibitors (MAOIs). However, unlike MAOIs, chronic SAMe treatment was not associated with changes in plasma MHPG. Exaggerated standing NE is found in depressed patients; SAMe may reduce this abnormal response, providing a clue for its mechanism of action in depression.
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PMID:Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers. 396 Oct 29

Synthesis of an S-adenosylmethionine-cleaving enzyme evoked by infection of Escherichia coli with phage T3 was independent of the multiplicity of infection with the wild type, T3 sam(+). It was depressed, however, by mixed infection with related phages genetically incapable of directing enzyme production, such as T3 sam(-), or phage T7. The depressor effect of enzymatically incompetent genomes depended on their proportion among the input phage and not on their absolute multiplicity. The effect was more pronounced with homologous, enzymatically incompetent phage (T3 sam(-)) than with heterologous phage (T7). After ultraviolet irradiation, enzymatically incompetent genomes lost their depressing power; at a survival level of 10(-7), no depression by either homologous or heterologous phage upon T3 sam(+)-directed enzyme synthesis was detected.
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PMID:Synthesis of an S-adenosylmethionine-cleaving enzyme in T3-infected Escherichia coli and its disturbance by co-infection with enzymatically incompetent bacteriophage. 491 33

S-adenosylmethionine (SAM) has antidepressant properties. The commonest neuropsychiatric complication of severe folate deficiency is depression. These independent observations suggest that methylation in the nervous system may underlie the expression of mood and related processes and may be implicated in some affective disorders; suggest new biological approaches to the understanding and treatment of some affective disorders; and may explain why methionine sometimes aggravates schizophrenia.
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PMID:Methylation and mood. 614 53


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