B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline

Neurosci Biobehav Rev. 2014 Nov;47:307-20. doi: 10.1016/j.neubiorev.2014.08.006. Epub 2014 Aug 27.


The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine β synthase (CβS), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations. This review discusses previous findings from clinical studies and highlights gaps in knowledge. Future studies assessing B vitamin-associated polymorphisms must take into account not just traditional demographics, but subjects' overall diet, relevant biomarkers of nutritional status and also analyze related genetic factors that may exacerbate behavioral effects or nutritional status.

Keywords: Alzheimer's disease; Autism; Dementia; Folate; Genetics; Geriatric depression; Memory; Mood; Nutrition; Vitamin B12; Vitamin B6; Vitamin B9.

Publication types

  • Review

MeSH terms

  • Cystathionine beta-Synthase / genetics*
  • Cystathionine beta-Synthase / metabolism
  • Ferredoxin-NADP Reductase / genetics*
  • Ferredoxin-NADP Reductase / metabolism
  • Genetic Association Studies
  • Genotype
  • Humans
  • Mental Disorders / genetics*
  • Mental Disorders / metabolism
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Polymorphism, Single Nucleotide*
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • Vitamin B Complex / metabolism*


  • Receptors, Cell Surface
  • transcobalamin receptor
  • Vitamin B Complex
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Cystathionine beta-Synthase