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)

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

Deficiencies of specific vitamins produce consistent symptoms of psychiatric disorder. Thiamine deficiency, which is common in alcoholism, can produce confusion and psychotic symptoms, in addition to neurological signs. Vitamin B12 and folate deficiency may contribute symptoms of disorientation, depression or psychosis; their measurement is a part of routine dementia work-ups. Pyridoxine deficiency results in seizures, although the effects of exogenously administered pyridoxine are not clearly understood in depression and anxiety - the disorders in which it is most frequently used clinically. The use of vitamins has been most prominent in psychiatry in the treatment of schizophrenia, where large doses of nicotinic acid were initially given alone and later combined with other vitamins and minerals. Several theoretical models were described to support the use of vitamins in schizophrenia. These included: the parallels of schizophrenia to the psychiatric symptoms of pellagra; hypotheses of a defect in adrenaline metabolism; and the accumulation of psychotoxic substances which produce psychotic symptoms. Initially, positive results were reported over 30 years ago, but have not been replicated by thorough investigations. An extensive series of comprehensive placebo-controlled trials failed to show efficacy for any of the vitamin therapies tested. Although clearly less effective than antipsychotic drug treatment, vitamin therapy is not without risks - adverse effects have been reported with nicotinic acid, pyridoxine and vitamin C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vitamins in psychiatry. Do they have a role? 389 44

The effect of anticonvulsant drugs on folate metabolism and mental symptoms has been investigated extensively in hospital-based studies, but never before in the community or general practice setting. Blood count, serum vitamin B12, red blood cell (RBC), and serum folate were measured in a sample of 82 adult epileptic patients drawn from 5 group practices (14 general practitioners) in southeast London. All patients were receiving antiepileptic medication at the time of examination and were interviewed with a standardized measure of psychopathology. Serum folate values below the lower limit of the normal range (3-15 micrograms/L) were obtained in 9 (10.9%) subjects, and in 50 (60.9%) patients, serum folate concentrations were less than the mean (6.02 micrograms/L) for the whole sample. Macrocytosis was detected in 20 (24.3%) patients. RBC and serum folate levels were significantly correlated with one another, but not with vitamin B12 concentrations. Levels of RBC and serum folate were significantly lower in patients on polytherapy (n = 40) than in those on monotherapy (n = 42); the folate concentrations were also significantly lower in the group with psychiatric morbidity. The association between folate deficiency and affective morbidity was demonstrated for depression but not for anxiety. There was no relationship between serum vitamin B12 and psychiatric disturbance. These findings are discussed in the light of relevant literature regarding the mechanism of action of anticonvulsant drugs in folate depletion and the neuropsychiatric sequelae.
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PMID:Antiepileptic therapy, folate deficiency, and psychiatric morbidity: a general practice survey. 404 12

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

Indoles were measured in cerebrospinal fluid (CSF) from control patients, from patients suffering from folate deficiency, and from patients with vitamin B12 deficiency. The folate-deficient patients were classified according to whether they exhibited a neuropsychiatric syndrome, consisting of organic mental changes, polyneuropathy, and depression, which responded to folate administration. CSF 5-hydroxyindoleacetic acid was low in the vitamin B12-deficient patients and in those folate-deficient patients whose symptoms were not related to folate deficiency. CSF 5-hydroxyindoleacetic acid returned to normal with folate treatment in the patients exhibiting folate-responsive neuropsychiatric signs. The data indicate a close association between folate-responsive neuropsychiatric symptoms and changes in 5-hydroxytryptamine metabolism in the central nervous system.
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PMID:Effect of folic acid and vitamin B12 deficiencies on 5-hydroxyindoleacetic acid in human cerebrospinal fluid. 618 39

Samples of bone marrow from 33 Ghanaian children with homozygous sickle cell anaemia who presented with profound anaemia (haemoglobin less than 5 g/dl) were studied. The principal finding was depression of erythropoiesis (aplastic crisis) in 14 children and erythroid hyperplasia in 17. A splenic sequestration crisis was clinically diagnosed in the remaining two children. Stainable iron was absent in the marrow of 14 children and reduced in another five. Megaloblastic changes compatible with folate deficiency were present in 8 children. It is suggested that iron and folate deficiencies may complicate sickle cell anaemia in children living in geographical areas where nutritional deficiencies are prevalent.
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PMID:Bone marrow in sickle cell anaemia at time of anaemic crisis. 674 77

Subacute combined degeneration of the spinal cord is a rare neurologic complication of folate deficiency. Progressive gait disturbance, weakness, confusion, and depression developed in a 39-year-old man. He had taken phenobarbital for more than 2 years. He was bedbound, with new loss of position and vibration senses in the lower extremities. His hemoglobin was 2.9/dl, mean corpuscular volume 122 fl, vitamin B12 428 pg/ml, and folate 1 ng/ml. Peripheral blood and bone marrow showed megaloblastic anemia. Serum methylmalonic acid and homocysteine levels were consistent with folate deficiency, not B12 deficiency. Treatment with folate and packed erythrocytes resulted at 4 months in overall improvement, including walking. Position sense was restored, and vibration sense had become nearly normal. The authors found no cause for folate deficiency except phenobarbital.
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PMID:Case report: subacute combined degeneration of the spinal cord from folate deficiency. 748 26

Serum 5-MeTHF levels are reported in 26 subjects, before and after completing a course of ECT, and compared to 21 healthy volunteers. 5-MeTHF levels of depressed subjects were significantly lower than controls before and after ECT. There was no difference in 5-MeTHF levels between ECT responders and non-responders but folate deficiency was related to severity of depression before ECT. Serum 5-MeTHF was not related to treatment response and values remained markedly low even after a good response to treatment.
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PMID:5-Methyltetrahydrofolate level in the serum of depressed subjects and its relationship to the outcome of ECT. 785 58

A variety of studies indicate that folate deficiency is associated with the appearance of problems of a neuromuscular or neurological nature such as depression, muscular and mental fatigue, states of confusion and non-senile dementia, and that these processes improve fully or partly when the deficiency is corrected. Because of the role of folates in the reactions in synthesis of neuro-transmitter and elements of neuron structure, it is not surprising that a deficiency is associated with depression and other mental problems. Folates are involved in the synthesis of S-adenosylmethionine (SAM) which is the main contributor of methyl groups in the nervous system and whose action as an antidepressive agent is confirmed. They are also involved in the synthesis of glutamate which is an excitant neurotransmitter, and in the formation of puric and pyrimidic bases. An alternative mechanism for explaining the etiopathogenesis of folate deficiency in depression and other mental disorders involves the regeneration of tetrahydrobiopterin (THB) which is an essential cofactor in hydroxylation process in the brains of mammals. Folate deficiency is a common nutritional problem in many groups of the Spanish population and, given the role of this vitamin in the operation of the nervous system, we might consider the possibility that, in some case, folate deficiency may cause or aggravate some alterations to mental function.
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PMID:[The role of folates in the diverse biochemical processes that control mental function]. 791 91

5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic medication significantly improved clinical recovery in depressed patients with borderline or definite folate deficiency, and significantly reduced depressive symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive status was compared to Trazodone (TRZ) in normofolatemic elderly patients with mild to moderate dementia and depression. Ninety-six patients with dementia, scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100 mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory (RVM) test for immediate and delayed recall was evaluated before and after treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20 +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and 19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05 vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with depression: results of a double-blind multicenter study. 825 78


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