DepressionVitamin D levels

There are a number of studies reporting associations between serum 25(OH)D levels and prevalence of depression. Since they studied prevalence rather than incidence, they provide modest evidence of a role of vitamin D in affecting risk of depression. In such studies, it can’t be ruled out that serum 25(OH)D levels were related to disease state rather than contributing to disease state. The findings of some of these studies are summarized here.

In a population-based cohort study involving 1,282 elderly community residents in the Netherlands, elevated measures of depression were found associated with lower serum 25(OH)D levels:

Levels of 25(OH)D were 14% lower in 169 persons with minor depression and 14% lower in 26 persons with major depressive disorder compared with levels in 1087 control individuals (P < 0.001). Levels of PTH were 5% and 33% higher, respectively (P = 0.003). Depression severity (Center for Epidemiologic Studies Depression Scale) was significantly associated with decreased serum 25(OH)D levels (P = 0.03) and increased serum PTH levels (P = 0.008)1.

Another study from the Netherlands found a link between vitamin D receptor (VDR) gene variations and depression. (VDRs are activated by 1,25-dihydroxyvitamin D and control the expression of numerous genes):

Carriers of ApaI variant-allele and of haplotype 1 (baT) had better cognitive functioning together with less depressive symptoms. These associations could not be explained by differences in calcium levels, and by selective survival, since no associations between the VDR gene variants and calcium levels and mortality were observed2.

A study in England found:

Depressive symptoms were associated with clinical vitamin D deficiency (25(OH)D levels <10 ng/mL; present in 9.8%) independent of other covariates but not with broader deficiency states. This association was not modified by season of examination. Conclusion: Vitamin D deficiency is associated with late-life depression in northern latitudes3

This six-year observational study involving 531 women and 423 men aged 65 years and older from Italy that found that women with lower serum 25(OH)D levels developed increases in depression scores and had a greater risk of developing depressive mood:

Women with 25(OH)D less than 50 nmol/liter compared with those with higher levels experienced increases in CES-D scores of 2.1 (P = 0.02) and 2.2 (P = 0.04) points higher at, respectively, 3- and 6-yr follow-up. Women with low vitamin D (Vit-D) had also significantly higher risk of developing depressive mood over the follow-up (hazard ratio = 2.0; 95% confidence interval = 1.2-3.2; P = 0.005). In parallel models, men with 25(OH)D less than 50 nmol/liter compared with those with higher levels experienced increases in CES-D scores of 1.9 (P = 0.01) and 1.1 (P = 0.20) points higher at 3- and 6-yr follow-up. Men with low Vit-D tended to have higher risk of developing depressed mood (hazard ratio = 1.6; 95% confidence interval = 0.9-2.8; P = 0.1)4.  

There is indirect evidence of a risk of depression from low serum 25(OH)D levels from reports of the association of several vitamin D-sensitive diseases with increased risk of depression. In a study in California:

Postmenopausal women with prevalent vertebral fracture reported more depressive symptoms as assessed by the GDS than women without prevalent vertebral fracture (1.54 vs 1.26; p = 0.001). There was an absolute increase of 2.5% (p = 0.008) in the prevalence of probable depression (GDS score > or = 6) in women with prevalent fracture compared to those without prevalent fracture. The prevalence of probable depression was 4.1% among women without prevalent vertebral fracture and 6.6% in women with a prevalent vertebral fracture. The prevalence of probable depression was 3-fold higher in women with at least 3 prevalent vertebral fractures compared to women without prevalent fracture (12.8% vs 4.1%; p < 0.001)5

In a study conducted in Aleppo, Syria:

In women, predictors of depression were heart disease (OR = 3.95, 95% CI: 1.50-10.40), hypertension (OR = 2.92, 95% CI: 1.53-5.55), and kidney disease (OR = 2.96, 95% CI: 1.64-5.32). Depression comorbidity with any chronic disease decreased in higher socio-economic status (middle vs. low: OR = 0.28, 95% CI: 0.12-0.65; high vs. low: OR = 0.20, 95% CI: 0.05-0.81). In men, predictors of depression were rheumatism (OR = 7.10, 95% CI: 2.58-19.60) and respiratory disease (OR = 3.77, 95% CI: 1.23-11.60). Depression comorbidity decreased in residence in formal zones (OR = 0.22, 95% CI: 0.06-0.80)6

Recent evidence suggests a strong relationship between depression and Alzheimer’s disease:

A lifetime history of major depression has been considered as a risk factor for later development of Alzheimer’s disease. The presence of depressive symptoms can affect the conversion of mild cognitive impairment into Alzheimer’s disease. Neuritic plaques and neurofibrillary tangles, the two major hallmarks of Alzheimer’s disease brain, are more pronounced in the brains of Alzheimer’s disease patients with comorbid depression as compared with Alzheimer’s disease patients without depression7. [Caraci et al., 2010].

Low serum 25(OH)D level appears to be a risk factor for Alzheimer’s disease.

In a cross-sectional study in the United States:

Women, non-Hispanic blacks, persons living below poverty, persons who did not consume supplements, persons living in South and West regions and in urban areas, persons with higher BMI, and persons with current depression had higher prevalence of vitamin D deficiency compared to their counterparts. OR for having current depressive episodes in persons with serum vitamin D [less than or equal to]50 nmol/L is significantly higher relative to those with serum vitamin D [greater than or equal to]75 nmol/L (OR=1.85; P=0.021)8

Page last edited: 06 May 2011

References

  1. Hoogendijk, W. J. Lips, P. Dik, M. G. Deeg, D. J. Beekman, A. T. Penninx, B. W. Depression is associated with decreased 25-hydroxyvitamin D and increased parathyroid hormone levels in older adults. Arch Gen Psychiatry. 2008 May; 65 (5): 508-12.
  2. Kuningas, M. Mooijaart, S. P. Jolles, J. Slagboom, P. E. Westendorp, R. G. van Heemst, D. VDR gene variants associate with cognitive function and depressive symptoms in old age. Neurobiol Aging. 2009 Mar; 30 (3): 466-73.
  3. Stewart, R. Hirani, V. Relationship between vitamin D levels and depressive symptoms in older residents from a national survey population. Psychosom Med. 2010 Sep; 72 (7): 608-12.
  4. Milaneschi, Y. Shardell, M. Corsi, A. M. Vazzana, R. Bandinelli, S. Guralnik, J. M. Ferrucci, L. Serum 25-hydroxyvitamin D and depressive symptoms in older women and men. J Clin Endocrinol Metab. 2010 Jul; 95 (7): 3225-33.
  5. Silverman, S. L. Shen, W. Minshall, M. E. Xie, S. Moses, K. H. Prevalence of depressive symptoms in postmenopausal women with low bone mineral density and/or prevalent vertebral fracture: results from the Multiple Outcomes of Raloxifene Evaluation (MORE) study. J Rheumatol. 2007 Jan; 34 (1): 140-4.
  6. Kilzieh, N. Rastam, S. Maziak, W. Ward, K. D. Comorbidity of depression with chronic diseases: a population-based study in Aleppo, Syria. Int J Psychiatry Med. 2008; 38 (2): 169-84.
  7. Caraci, F. Copani, A. Nicoletti, F. Drago, F. Depression and Alzheimer’s disease: neurobiological links and common pharmacological targets. Eur J Pharmacol. 2010 Jan 10; 626 (1): 64-71.
  8. Ganji, V. Milone, C. Cody, M. M. McCarthy, F. Wang, Y. T. Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey. Int Arch Med. 2010 Nov 11; 3 (1): 29.