Accessibility statement

Is there a link between folate, folate metabolism and depression?

A link between low folate and depression was first postulated by Victor Herbert in 1961, when he induced in himself a state of dietary folate deficiency and described ‘insomnia, irritability, impaired memory and fatigue’. Since the advent of accurate assay techniques in the late 1960s, an association between folate deficiency and depression has been repeatedly described. The involvement of folate in DNA methylation and the synthesis of neurotransmitters (including serotonin - 5-hydroxytryptamine; 5-HT) in the central nervous system provides a biologically plausible mechanism for the link between folate and mood. Folate is cheap and relatively safe with a number of proven health benefits and fortification of foods with folate is mandatory in several countries (including the United States, Canada and Australia), and is being considered in others (including the United Kingdom). Thus the demonstration of a population-level benefit of folate, in terms of mental health and wellbeing might usefully inform these debates. We have previously found an association between depression and folate in a pooled sample of 15,315 cases and demonstrated that genetic variation in MTHFR, a key enzyme involved in folate metabolism, is associated with both depression and schizophrenia. However, the folate metabolic pathway is complex and has not been comprehensively investigated in relation to psychiatric disorders. We propose to use Mendelian randomisation and genetic epidemiology to more fully understand dietary associations and modifiable environmental risk factors in psychiatric disease.


Funder(s): Hull York Medical School
Start Date: 01-Mar-2007
Expiry Date: 29-Feb-2008


Internal staff

Mental Health and Addiction Research in the Department of Health Sciences