Vitamin B12 and Psychiatric Illness

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Author(s): 

Samia Sabeen, MD, MPH, and Suzanne Holroyd, MD

author affiliations:

Dr. Sabeen is Assistant Professor and Dr. Holroyd is Professor, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville.

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Vitamin B12 deficiency is a common occurrence in the elderly and is associated with delirium, dementia, depression, and psychosis. Psychiatric symptoms may occur in the absence of characteristic hematologic or neurologic symptoms suggestive of B12 deficiency. Because psychiatric symptoms can occur in low-to-moderate “normal” vitamin B12 levels, homocysteine or methylmalonic acid levels should also be checked in those with psychiatric symptoms. Importantly, dementia or cognitive decline become irreversible if not treated promptly. Psychosis appears to respond to vitamin B12 replacement, even after prolonged periods of a B12-deficient state, again pointing out the need to check for B12 deficiency in the elderly with psychosis. Future research and follow-up studies are needed. (Annals of Long-Term Care: Clinical Care and Aging 2009;17[3]:32-36)

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Cobalamin, commonly known as vitamin B12, is a member of the vitamin B complex family. Vitamin B12 plays an essential role in maintaining homeostasis in the nervous and the hematologic systems. Psychiatric symptoms are associated with deficiencies in vitamin B12 and can be difficult to diagnose, as the psychiatric manifestations can present without the hematologic or neurologic ones. This article reviews the association of psychiatric illness and vitamin B12 deficiency.

Biochemistry

To briefly review the biochemistry, two forms of vitamin B12, methylcobalamin and 5-deoxyadenosyl cobalamin, are active in the human body.1 Methylcobalamin is required for the synthesis of the enzyme methionine synthase via a methylation reaction. Methionine synthase is an enzyme required for the production of the amino acid methionine from homocysteine. Thus, in vitamin B12 deficiency, the level of homocysteine increases secondary to decreased utilization.2 The other form of cobalamin, 5-deoxyadenosyl cobalamin, is involved in the transformation of L-methylmalonyl-CoA to succinyl-CoA.3 This is essential for the synthesis of hemoglobin in the production of red blood cells and for the production of energy from fats and protein, as well as fatty acid production. This latter process plays an integral part in the formation and maintenance of the myelin sheath. Methylmalonic acid (MMA) is a metabolite of aforementioned enzymatic process that, in the situation of B12 deficiency, will be increased. It is noted then that increased levels of both homocysteine and MMA can be markers of functional vitamin B12 deficiency,4 which can occur even in the presence of “normal” vitamin B12 serum levels.

The literature review was conducted on PubMed, National Library of Medicine, and The Cochrane Library using the following terms: B12 deficiency, psychiatric illness and B12 deficiency, dementia and B12 deficiency, methylmalonic acid, homocysteine, reversible dementia, mood disorder, and B12 deficiency.

Causes of Vitamin B12 Deficiency

Vitamin B12 has a very specific mechanism in order to be absorbed by the body. The acidic environment of the stomach frees the vitamin from food, where it binds with R protein and travels to the small intestine. In the small intestine, the R protein is degraded by pancreatic enzymes facilitated by the alkaline environment. Intrinsic factor (IF) secreted by specialized stomach cells binds with vitamin B12 in the terminal ileum, and the vitamin B12-IF complex is then absorbed.

References: 


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