Folate and cobalamin in psychiatric illness

Compr Psychiatry. 1997 Nov-Dec;38(6):305-14. doi: 10.1016/s0010-440x(97)90925-1.


The linkage of cobalamin and folate deficiency to psychiatric illness has been studied and debated since these vitamins were first discovered in the 1940s. The clinical relevance of these deficiencies remains the subject of investigation and scholarly discussion. This article reviews case reports and studies derived from a MEDLINE search for English-language articles related to folate, cobalamin, and psychiatric illness. Emphasis is given to clinical research and recent developments. Preclinical evidence for direct effects of folate and cobalamin on brain functioning is compelling, and numerous associations of their deficiencies to psychiatric illness are evident. These vitamin deficiencies may typically present initially with psychiatric symptoms, but any direct causal relationship to specific neuropsychiatric illnesses are not well defined. The relationship of these vitamins in dementia is significant, but they may only rarely be a cause of truly reversible dementia. Folate deficiency appears most tightly connected with depressive disorders, and cobalamin deficiency with psychosis. Contrary to intuition, vitamin deficiencies appear to occur infrequently with eating disorders. Other diagnoses have been investigated much less extensively. The diagnosis and management of these deficiencies in the context of neuropsychiatric illness is still a matter of discussion. The quality of clinical research in this area is improving, but there are many unanswered questions that affect clinical practice. Clinicians should remain vigilant to the possibility of deficiencies of folate and cobalamin in diverse psychiatric populations. Normal hematological indices do not rule out the deficiencies. Further study is needed to refine the detection and clinical management of these vitamin deficiencies in psychiatric populations.

Publication types

  • Review

MeSH terms

  • Brain / physiopathology
  • Dementia / etiology
  • Dementia / physiopathology
  • Depressive Disorder / etiology
  • Depressive Disorder / physiopathology
  • Folic Acid / physiology
  • Folic Acid Deficiency / complications*
  • Folic Acid Deficiency / physiopathology
  • Humans
  • Neurocognitive Disorders / etiology*
  • Neurocognitive Disorders / physiopathology
  • Neurotransmitter Agents / physiology
  • Risk Factors
  • Vitamin B 12 / physiology
  • Vitamin B 12 Deficiency / complications*
  • Vitamin B 12 Deficiency / physiopathology


  • Neurotransmitter Agents
  • Folic Acid
  • Vitamin B 12