The Relationship Between MDD and Lower Vitamin D Levels in Women

Are lower vitamin D levels in women related to depressive mood?

A recent study suggests vitamin D, via its effects on the brain, may play a pivotal role in the pathophysiology of major depressive disorder (MDD).1

Depression often follows a seasonal pattern, peaking in summer and winter.2 Vitamin D, through its action on the brain, might account for this link between seasonal light changes and seasonal mood swings.3 Key for neuronal development and brain function, vitamin D exerts its effects on the brain via binding to vitamin D receptors,4 distributed in the prefrontal cortex, cingulate cortex, and limbic system.5

To discover more, investigators took a look at the association between gender, serum concentration of vitamin D, and depression in a large sample of 122 participants with MDD and 119 healthy controls. Resting-state functional MRI data were collected with independent component analysis adopted to examine large-scale inter- and intranetwork functional connectivity. Serum concentration of vitamin D and depression symptoms were also assessed.

Investigators observed 4 main findings.

1. There was a significant group-by-gender interaction effect on serum concentration of vitamin D. Participants with MDD exhibited lower vitamin D levels than control participants, specifically in females rather than males.

2. Female participants with lower serum concentration of vitamin D had poorer cognitive performance (ie, prospective memory and sustained attention).

3. There was a connection between MDD-related functional network connectivity changes and serum concentration of vitamin D, as well as depression and anxiety symptoms in female participants with MDD.

4. MDD- and serum concentration of vitamin D-related functional network connectivity alterations mediated the associations between vitamin D levels and cognition in females.

Investigators found that vitamin D insufficiency and deficiency was more common in females than males. MDD patients had significantly lower vitamin D levels relative to healthy controls, again specifically in females. This gender difference could be a result of insufficient sunlight exposure, higher BMI, more fat tissue, and more sedentary life in females relative to males. Overall, this may suggest a female-specific involvement of vitamin D in the pathogenesis of depression.

“More broadly, these findings may inform a novel conceptualization that adjuvant vitamin D supplementation therapy may yield clinical benefits in improving treatment outcomes in female patients with MDD,” concluded the study authors.1


1. Zhu D, Zhao W, Cui S, et al. The relationship between vitamin D, clinical manifestations, and functional network connectivity in female patients with major depressive disorder. Front Aging Neurosci. 2022;14:817607.

2. Wehr TA, Rosenthal NE. Seasonality and affective illness. Am J Psychiatry. 1989;146(7):829-839.

3. Berk M, Sanders KM, Pasco JA, et al. Vitamin D deficiency may play a role in depression. Med Hypotheses. 2007;69(6):1316-1319.

4. Ryan JW, Anderson PH, Morris HA. Pleiotropic activities of vitamin D receptors - adequate activation for multiple health outcomes. Clin Biochem Rev. 2015;36(2):53-61.

5. Eyles DW, Smith S, Kinobe R, et al. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005;29(1):21-30.