Serena Masellis 12/01/2014

VITAMIN B ₁₂ AND DEPRESSION

The role of the deficiency of Vitamin B ₁₂ in the insurgence or the worsening of the Major Depressive Disorder isn’t still totally clear, but it is related with the biochemical metabolism of this vitamin and its role as cofactor in the metabolism of the amino acid "Methionine":http://en.wikipedia.org/wiki/Methionine.

MethylCobalamin and Methyl tetrahydrofolate are necessary cofactors that permit the transmethylation of Homocysteine in Methionine.  Methyltetrahydrofolate, in fact, delivers methyl groups to form the active methyl form of vitamin B12 that is required for methylation of homocysteine. Deficiency of vitamin B ₁₂  or folic acid causes increased levels of circulating homocysteine (E. Reynolds—Vitamin B12, folic acid, and the nervous system).

The role of vitamin B ₁₂  in depression is due to its action in transmethylation reactions, which are crucial for the formation of neurotransmitters (e.g. serotonin, epinephrine, nicotinamides, purines, phospholipids).
Low levels of folate or vitamin B ₁₂ can disrupt transmethylation reaction, leading to an accumulation of "homocysteine": http://en.wikipedia.org/wiki/Homocysteine (hyperhomocisteinemia) and to an impaired metabolism of neurotransmitters (especially the hydroxylation of Dopamine and Serotonin from Tyrosine and "Tryptophan": http://en.wikipedia.org/wiki/Tryptophan), phospholipids, myelin, and receptors. The lowering of the synthesis of neurotransmitters, expecially of Serotonin and Dopamine, causes a lower release by neurons and this is one of the principal causes of the insurgence of the Major Depressive Disorder.
Low plasma B ₁₂  and low plasma folate has been found in studies of depressive patients. Furthermore, some studies have shown that low folate levels are linked to a poor response of antidepressant treatment. Other studies also suggest that a high vitamin B ₁₂ status may be associated with better treatment outcomes. The increment of the vitamin B ₁₂ levels in the treatment of this neurogical disorder has been associated through clinical trials in the improvement of the result of the farmacologycal treatment in the patients (Durant et al.--Psychiatric manifestation of vitamin B12 deficiency: a case report).
Some Clinical Trials made on patients affected by depression have reported results that show how a supplement of Cobalamin in patients which had not responded to the anti-depressive treatment, improved their results (N. Kate et al.--Does B12 deficiency lead to lack of treatment response to conventional antidepressants).

See also Vitamin B12

Correlation between depression and folic acid pahtways.

There are a lot of studies in the letterature about this point.
We have selected some examples:

Association between depressive symptoms and serum concentrations of homocysteine in men: a population study (2004)

The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis (2006)

Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review (2007)

Homocysteine and Depression in Later Life (2008)

There is a current Australian trial that want to demonstrate the benifit of folic acid and B vitamin supplementation in the MDD terapy!!!!
The B-VITAGE trial: A randomized trial of homocysteine lowering treatment of depression in later life (2010)