The relationship of severity of depression with homocysteine, folate, vitamin B12, and vitamin D levels in children and adolescents Erman Esnafoglu 1 & Deniz Deniz Ozturan 2 1 Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ordu University, Ordu, Turkey 2 Department of Psychiatry, Faculty of Medicine, Ordu University, Ordu, Turkey Background: Depression is a heterogeneous disorder and is thought to develop as a result of complex interac- tions 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 Æ SD = 15.08 Æ 1.46) and 43 control subjects (31 female, 12 male; mean age Æ SD = 14.41 Æ 2.32) without any DSM-5 diagnosis. Each subject completed a sociodemographic form, Childhood Depression Inventory, State-Trait Anxiety Inven- tory 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 homocys- teine 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 pathogene- sis 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; folate; vitamin B12; vitamin D; depression Introduction Depressive disorder in children and adolescents is com- monly a familial recurring disorder. It is related to signif- icant complications like increased risk of suicide, substance abuse, exposure to negative life experiences, legal problems, physical diseases, early pregnancy, and worsened work, academic and psychosocial functioning (Birmaher & Brent, 2007). As a result, explaining the etiopathogenesis of depressive disorder in children and adolescents gains importance. The prevalence is esti- mated as 0.4%–2.5% in children and 0.4%–8.3% in ado- lescents but the etiology of depressive disorder has not been fully explained (Birmaher et al., 1996). Depression is a heterogeneous disorder and is thought to develop as a result of complex interactions between genetic and environmental factors (Rao, 2013). To date, one-carbon metabolism dysfunction has been researched mainly in neuropsychiatric disorders in adulthood and the geriatric period (Clarke et al., 1998; Selhub, Bagley, Miller, & Rosenberg, 2000). Addition- ally, it has been proposed that abnormalities related to one-carbon metabolism are involved in psychiatric dis- eases like schizophrenia and bipolar disorder in the adult period (Haidemenos et al., 2007; Ozbek et al., 2008). The studies conducted in the childhood period © 2020 Association for Child and Adolescent Mental Health Published by John Wiley & Sons Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main St, Malden, MA 02148, USA Child and Adolescent Mental Health Volume **, No. *, 2020, pp. **–** doi:10.1111/camh.12387