The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents

Child Adolesc Ment Health. 2020 Nov;25(4):249-255. doi: 10.1111/camh.12387. Epub 2020 Apr 18.


Background: Depression is a heterogeneous disorder and is thought to develop as a result of complex interactions between genetic and environmental factors. One-carbon metabolism that includes vitamin B12, folic acid, and homocysteine has been investigated in psychiatric disorders like depression. In recent years, vitamin D has also been considered to contribute to psychiatric disorders. In this study, serum levels of folate, vitamin B12, and homocysteine related to one-carbon metabolism and vitamin D were investigated in children and adolescents with depression and to assess possible roles in depression pathogenesis.

Methods: The study included 89 children and adolescents with depression (69 female, 20 male; mean age ± SD = 15.08 ± 1.46) and 43 control subjects (31 female, 12 male; mean age ± SD = 14.41 ± 2.32) without any DSM-5 diagnosis. Each subject completed a sociodemographic form, Childhood Depression Inventory, State-Trait Anxiety Inventory 1-2 and measured serum folate, vitamin B12, homocysteine, and 25-OH vitamin D levels.

Results: There was no significant difference between the groups in terms of folate levels (p = .052). In the patient group, the vitamin B12 and vitamin D levels were clearly low (p values for both levels were <.001), while homocysteine levels were found to be remarkably high (p < .001). In addition, there was a negative correlation between depression severity and vitamin B12 and vitamin D, while a positive correlation was found with homocysteine.

Conclusions: The results of the study show that vitamin B12 deficiency or insufficiency and elevated homocysteine may contribute to the etiopathogenesis of depression. Additionally, it was shown that lower vitamin D levels may be associated with depression.

Key practitioner message: Depression of children and adolescents is associated with the interaction of environmental and genetic factors. Homocysteine, vitamin B12, and folate related to one-carbon metabolism are associated with psychiatric disorders such as depression in adulthood. Vitamin D also contributes to psychiatric disorders pathogenesis. There are not enough studies in the literature about these parameters in children with depression. Low vitamin B12 and vitamin D levels and increased homocysteine levels may play a role in the pathogenesis of depression in children and adolescents. Investigation of vitamin B12, folate, homocysteine, and vitamin D levels are recommended in children and adolescents with depression.

Keywords: One-carbon metabolism; depression; folate; vitamin B12; vitamin D.

MeSH terms

  • Adolescent
  • Child
  • Depressive Disorder / blood*
  • Depressive Disorder / etiology
  • Depressive Disorder / physiopathology*
  • Female
  • Folic Acid / blood*
  • Folic Acid Deficiency / complications
  • Homocysteine / blood*
  • Humans
  • Male
  • Severity of Illness Index
  • Vitamin B 12 / blood*
  • Vitamin B 12 Deficiency / complications
  • Vitamin D / blood*


  • Homocysteine
  • Vitamin D
  • Folic Acid
  • Vitamin B 12