Homocysteine, folate, methylation, and monoamine metabolism in depression

Abstract

Objectives-Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, diYculties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. Methods-In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. Results-Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. Conclusions-Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement. (J Neurol Neurosurg Psychiatry 2000;69:228-232)

Homocysteine, methylenetetrahydrofolate reductase and risk of schizophrenia: a meta-analysis

“…Hyperhomocysteinemia is not specific for schizophrenia, and has been reported as a risk factor for various diseases such as cardiovascular diseases, 25 neural tube defects, 45 and neuropsychiatric disorders including Alzheimer's disease, 46 Parkinson's disease 47 and depression, [48][49][50] stressing the pivotal role of the single-carbon mechanism. The pathogenic mechanisms underlying these moderate hyperhomocysteinemic diseases are not yet fully understood.…”

Hyperhomocysteinemia and DNA hypomethylation, reduced the monoamines synthesis in depression: A case control study

“…However, deprived intake of essential nutrition, which supply the methyl groups from methyl folate or vitamin B12 and cause hyperhomocysteinemia or high level of tHcy.HHcy in depression indicates a breakdown in the methylation of homocysteine to methionine or cysteine, taurine, and glutathione -a B6 -dependent process and causes oxidative stress resulting in neurological and vascular damage and lead to disturbance in the optimal biosynthesis of neurotransmitters and cell signalling or cell repair and also disturbed the level of MAO in brain, its higher concentration as neurotoxic [24]. It is associated with various cardiovascular and other neurologicaldisorders, including cognitive impairment and dementia conversely, accumulation of tHcy involved in the path physiology of depression and reduces the level of neurotransmitters such as serotonin, dopamine, noradrenalin, and γ aminobutyric acid (GABA) are often associated with depression [10,[12][13][14]25,[32][33][34].…”

“…Several studies have supported the essential supplements (nutrients) are involved in mood regulation and suggest a potential role for supplemental nutrients in mitigating the symptoms of depression. Sometimes tyrosine acts as a precursor to phenylalanine and are converted into dopamine and norepinephrine [2,12,[29][30][31]. Some other studies have suggested the amino acids tryptophan, tyrosine, phenylalanine, and methionine are often helpful in treating many mood disorders including depression through increasing the concentration of monoamines in the brain [11,14,32].…”

“…Innovative discipline is nutritional neuroscience, focusing on the fact that nutritional factors are interacting with cognition, behavior, and emotions. Some nutritional supplement such as folic acid and vitamin B12 & B6 may be determinants of mental illness or depression and deficiencies of these vitamins have been implicated in the etiology and treatment of both depression and other neuropsychological disorders, however, folate and vitamin B12 have fundamental roles in central nervous system (CNS) function [12][13][14][15][16].…”

Plasma Homocysteine Concentraton according to the Depression and Degree of Stress

“…있는 것을 보여주고 있다 (Bell IR et al, 1991;Bottiglieri T et al, 2000). 또한 우울증이 있는 사람이 허혈성 심질환으로 사망하는 비율이 높은 이유가 혈중 호모시스테인 농도가 높은 것일 수 있다는 연구도 있으나 (Surtees PG et al, 2008) 아직까지 호모시스테인이 직접적으로 우울증의 원인인지 는 아직 불분명한 것으로 알려져 있다 (Bottiglieri T, 2005).…”