Elsevier

Psychiatry Research

Volume 227, Issue 1, 30 May 2015, Pages 46-51
Psychiatry Research

Associations between vitamin D levels and depressive symptoms in healthy young adult women

https://doi.org/10.1016/j.psychres.2015.02.016Get rights and content

Highlights

  • Depressive symptoms and vitamin D were measured in 185 healthy women across 4 weeks.

  • Significant symptoms and vitamin D insufficiency were common, and differed by season.

  • Initially low vitamin D levels were associated with clinically significant depressive symptoms across follow-up.

  • Between-subjects differences in depression by season were partially explained by seasonal changes in vitamin D.

  • Racial-ethnic differences in depression were partially explained by group differences in vitamin D levels.

Abstract

There have been few studies of whether vitamin D insufficiency is linked with depression in healthy young women despite women׳s high rates of both problems. Female undergraduates (n=185) living in the Pacific Northwest during fall, winter, and spring academic terms completed the Center for Epidemiologic Studies Depression (CES-D) scale weekly for 4 weeks (W1–W5). We measured serum levels of vitamin D3 and C (ascorbate; as a control variable) in blood samples collected at W1 and W5. Vitamin D insufficiency (<30 ng/mL) was common at W1 (42%) and W5 (46%), and rates of clinically significant depressive symptoms (CES-D≥16) were 34–42% at W1–W5. Lower W1 vitamin D3 predicted clinically significant depressive symptoms across W1–W5 (β=−0.20, p<0.05), controlling for season, BMI, race/ethnicity, diet, exercise, and time outside. There was some evidence that lower levels of depressive symptoms in Fall participants (vs. Winter and Spring) were explained by their higher levels of vitamin D3. W1 depressive symptoms did not predict change in vitamin D3 levels from W1 to W5. Findings are consistent with a temporal association between low levels of vitamin D and clinically meaningful depressive symptoms. The preventive value of supplementation should be tested further.

Introduction

Depression is a major public health problem that is linked with premature death by suicide and other causes (Chesney et al., 2014), and disability and economic burden (Greenberg et al., 2003). According to a nationally representative study lifetime prevalence of major depressive disorder was 25% among American women (vs. 16% for men; Kessler et al., 2003). Moreover, a longterm repeated measures study through age 30 years recently indicated the cumulative incidence rate was a staggering 63.4% for women (vs. 34.7% among men; Rohde et al., 20131). Thus, depression places an enormous health burden on young women, in particular.

Some epidemiological studies suggest low levels of vitamin D [25-hydroxyvitamin D or 25(OH)D] may contribute to depression. Proposed biological mechanisms for this association include that vitamin D: 1) has receptors that are distributed in brain areas involved in emotional processing and affective disorders (Eyles et al., 2013, Kesby et al., 2011); 2) regulates serotonin synthesis via transcriptional activation of the tryptophan hydroxylase 2 gene (Patrick and Ames, 2014); and 3) impacts innate immunity and the production of proinflammatory cytokines that in turn influence mood by activating the stress response (Capuron and Miller, 2004, Raison et al., 2006, Silverman et al., 2005, Zhang et al., 2012).

However, evidence for an association between vitamin D sufficiency status and depression is inconclusive. Meta-analyses (Li et al., 2013, Shaffer et al., 2014) indicate vitamin D supplementation trials have not shown significant effects on depression. Likewise, a meta-analysis of 10 cross-sectional studies indicated the odds of depression were not significantly elevated among those with low levels of vitamin D compared to others (Anglin et al., 2013). Importantly, researchers often have not adjusted for important confounders, and have used definitions of vitamin D insufficiency or deficiency that are based on risk for medical conditions. These cut-offs may be arbitrary with respect to risk for depression, and thus their use in research may have contributed to null findings. Indeed, levels (vs. cut-offs) of vitamin D in 18–65 year olds were found to be lower among participants with current or remitted depression relative to controls, and associated with symptom severity and a worsened 2-year course (Milaneschi et al., 2013). Thus, alternative measurement and design approaches are needed.

Another problem with the current evidence base on relations between vitamin D and depression is that findings may not generalize to healthy young women. Indeed, most experimental and observational research concerns older or medically compromised populations (e.g., Jorde et al., 2008; Parker and Brotchie, 2011; Sanders et al., 2011). In an important exception, Ganji et al. (2010) found that rates of current depression were associated with vitamin D deficiency in a nationally representative U.S. sample of young adults. Of note, however, they did not control for season of the year or some other important confounds.

Studying young healthy women minimizes the possibility that observed associations between vitamin D and depression are explained by significant health conditions, age variation, or gender. However, a number of potential confounders remain, including race/ethnicity, health behaviors, and season (Ganji et al., 2010, Hollis, 2005, Norman, 1998). Regarding seasonal effects, humans can generate sufficient vitamin D subcutaneously when exposed to sunlight (Norman, 1998). During non-summer months, however, meteorological and behavioral factors can limit skin exposure to sunlight and lead to decreased production of vitamin D3 and rapid depletion of body reserves. For this reason, individuals from a range of climates often become vitamin D insufficient in the winter and do not regain sufficiency for months (Holick, 2007).

Given that vitamin D levels vary with season of the year and may have an inverse relationship with depressive symptoms, some have suggested vitamin D may play a role in explaining seasonal affective disorder (SAD) and seasonality (the milder spectrum of sensitivity of mood and behavior to seasonal changes). Leading models of SAD emphasize the disruption of vulnerable individuals׳ circadian rhythms following seasonal changes in day length (Rohan et al., 2009). However, day length is confounded with other factors (intensity of solar radiation, cloud cover, clothing) that explain seasonal variation in vitamin D. Thus, it is possible that seasonal changes in vitamin D levels account for some of the seasonal variation in depressive symptoms. Despite the intuitive appeal of this theory, it has not been studied extensively. In a case control study Kjærgaard et al., 2012 found that participants from Northern Norway showed a range of seasonality scores, but scores did not differ for those with insufficient versus sufficient vitamin D levels. Furthermore, they found that seasonality scores did not decrease more following high-dose vitamin D supplementation than following placebo. Reviews of the topic yield little conclusive support for a role of vitamin D in the etiology and treatment of SAD or seasonality (see Bertone‐Johnson, 2009; Parker and Brotchie, 2011). However, further research is needed using larger samples and stronger study designs.

The present study builds on the extant literature in several ways. First, we test whether vitamin D levels are associated with depressive symptoms in healthy young women; such women rarely have been considered in this literature despite their high risk for depression and the straightforward implications such research may have for prevention. Second, we use a latent variable to estimate clinically significant depressive symptoms over a 4 week period, a measurement approach that is more reliable than using a cut-off score based on a single assessment. Third, in addition to controlling for participant characteristics and health behaviors, we control for vitamin C levels to evaluate the specificity of the vitamin D path of interest. Finally, we integrate prior findings on seasonal and racial/ethnic group differences in the separate literatures on vitamin D sufficiency and depressive symptoms (Eisenberg et al., 2013, Ganji et al., 2010, Hollis, 2005, Norman, 1998). That is, we hypothesize that any differences in depressive symptoms by season or race/ethnicity will be explained in part by group differences in vitamin D levels (i.e., indirect effects).

Section snippets

Participants

Participants were 185 undergraduate women ages 18–25 years [mean (S.D.)=19.66 (1.56)] who were enrolled at a large university in the northwestern United States. Inclusion criteria for participation were: female gender; not currently pregnant; self-reported weight of 110 pounds or greater2; and willingness to complete web-based surveys and contribute two 10-mL blood samples. From the initial sample of 190 enrolled participants, 5

Descriptive statistics

Descriptive statistics are reported in Table 1. At each of five observations, 34–42% of participants reported clinically significant depressive symptoms. Rates of vitamin D insufficiency [n=58 (31%) at 20–29.99 ng/mL] and deficiency [n=19 (10%) at <20 ng/mL] at baseline and at 4 week follow-up [n=57 (31%) insufficient and n=27 (15%) deficient, out of 182 participants] were common. Antidepressant medication and multivitamin use were reported by 10% and 42% of participants, respectively. Statistics

Discussion

Vitamin D3 levels were negatively related to clinically significant depressive symptoms across five weekly assessments in healthy young adult women. These findings are important given that previous studies often have concerned older adults and special medical populations, or have not controlled for important confounds (Ganji et al., 2010, Jorde et al., 2008, Sanders et al., 2011). Without an experimental design we cannot conclude that low vitamin D levels caused depressive symptoms (or that

Conflict of interest

David T. Zava is CEO of ZRT Laboratory. The authors have no other conflicts to disclose.

Contributors

David Kerr conceptualized the study, served as PI on the grant and study, conducted the data analyses, and had primary responsibility for writing the manuscript. David Zava supervised the vitamin D assays, wrote critical portions of the methods and limitations, and edited and approved the manuscript. Walter Piper played a chief role in recruiting participants, and the collection, processing, and storage of blood samples; contributed to study conceptualization and literature review; and reviewed

Acknowledgments

The authors thank phlebotomy and lab staff Mary Garrard, Deborah Hobbs, Taylor Wolf, Teresa Wolfe, and Jill Redmond for their assistance with data and sample collection, and David Kimball for technical assistance on vitamin D assays. This study was supported by Grant from the John C. Erkkila, M.D. Endowment for Health and Human Performance of Good Samaritan Hospital Foundation, and by Grant number P30 ES000210 from the National Institute of Environmental Health Sciences (NIEHS). Neither funding

References (36)

  • E.R. Bertone‐Johnson

    Vitamin D and the occurrence of depression: causal association or circumstantial evidence?

    Nutrition Reviews

    (2009)
  • S.J. Blalock et al.

    Development and assessment of a short instrument for assessing dietary intakes of calcium and vitamin D

    Journal of the American Pharmacists Association

    (2002)
  • E. Chesney et al.

    Risks of all-cause and suicide mortality in mental disorders: a meta-review

    World Psychiatry

    (2014)
  • K. Choi et al.

    Prevalence and characteristics of indoor tanning use among men and women in the United States

    Archives of Dermatology

    (2010)
  • D. Eisenberg et al.

    Mental health in American colleges and universities: variation across student subgroups and across campuses

    The Journal of Nervous and Mental Disease

    (2013)
  • V. Ganji et al.

    Serum vitamin D concentrations are related to depression in young adult US population: the Third National Health and Nutrition Examination Survey

    International Archives of Medicine

    (2010)
  • P.E. Greenberg et al.

    The economic burden of depression in the United States: how did it change between 1990 and 2000?

    The Journal of Clinical Psychiatry

    (2003)
  • M.F. Holick

    Vitamin D deficiency

    The New England Journal of Medicine

    (2007)
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