Low vitamin D and depression: A systematic review and meta-analysis

Jonathan A. Shaffer, PhD; Donald Edmondson, PhD, MPH; Lauren Taggart Wasson, MD; Louise Falzon, PGDipInf; Kirsten Homma, BA; Peter Li, Nchedochukwu Ezeokoli,

Karina W. Davidson, PhD

Acknowledgments American Heart Association Clinical Research Program Award

12CRP8870004 Thank you to Dr. Joe Schwartz for guidance with analyses.

No conflicts of interest to disclose

The Vast Public Health Impact & Unknown Pathogenesis of Depression

Associated with significant disability, mortality, and healthcare costs

Third leading cause of disability in high-income countries Affects approximately 840 million people worldwide 1

Unknown underlying pathophysiology Possible role for vitamin D deficiency?

1 WHO. Mental Health Gap Action Programme: Scaling Up Care for Mental, Neurological, and Substance Use Disorders. WHO, 2008.

2 N Engl J Med 2007;357:266-81

The Vast Public Health Impact of Vitamin D Deficiency

Vitamin D, a neurosteroid hormone with numerous skeletal and non-skeletal functions Mostly produced in body following

exposure to and penetration of skin by ultraviolet B radiation

Public health impact

1 billion people worldwide 40 to 100% of U.S. and European

community-dwelling elderly men and women2

N Engl J Med 2007;357:266-81

Role of Vitamin D Deficiency in Depression: Biological Plausibility

Vitamin D receptors (VDR) and enzymes required for vitamin D metabolism are abundant throughout the brain Neurons and glia Substantia nigra, limbic

system, cortex, cerebellum

May stimulate neurotrophins, which regulate neuronal development

Role of Vitamin D Deficiency in Depression: Empirical Support

Numerous cross-sectional studies Mixed support Reverse causation

A few prospective studies

Numerous narrative reviews No systematic, quantitative reviews *

Objective of the Current Study

To conduct a systematic review and meta-analysis of prospective cohort studies of the association of vitamin D deficiency with onset of depression in non-depressed individuals

Methods

Electronic databases searched through May 2012 (MEDLINE, EMBASE, CINAHL, AMED PsycINFO) Two independent reviewers of titles, abstracts, and/or full-text

Extraction of demographic, clinical, and methodologic variables

Definitions of vitamin D deficiency Type of depression assessment Method of assessing vitamin D

Heterogeneity assessment using the Cochrane Q statistic

Methods: Search Strategy Search terms for MEDLINE: exp depression OR exp depressive

disorders OR depress$.tw, exp vitamin d OR exp vitamin D deficiency OR vitamin d.tw. OR 25-hydroxyvitamin D.tw. OR cholecalciferol.tw. OR dihydrotachysterol.tw. OR ergosterol.tw.

Adapted for other databases

Search of reference lists from relevant studies

Related Articles search in PubMed and ISI Web of Science

Results: Study Selection

Results: Description of Included Studies Source, y

N

Mean age,

years

Female

Low

vitamin D

Definition

of low vitamin D

Type of

vitamin D assessment

Length of

follow-up

Site

Depression measure/ definition

Chan et al., 2011

629 72.8 0% 5.2% 25(OH)D

Results: Magnitude & Consistency of the Depression-Vitamin D Deficiency Association

2.3-fold increased risk of developing depression among individuals with vitamin D deficiency compared to those with sufficient vitamin D (95% confidence interval, 1.6 3.2, p < 0.001)

Effect size estimates ranging from 0.45 to 2.70, but no statistically significant heterogeneity (Q2 = 2.0, p = 0.36)

Forest Plot of the Association of Vitamin D Deficiency and Incident Depression

Forest Plot of the Association of Vitamin D Deficiency and Incident Depression *

* British J Psychiatry 2013;202:100-107

Conclusions Vitamin D deficiency is associated with an increased risk of

developing depression, but more prospective observational studies may be needed. Unclear prospective associations in adults younger than 50

Efficacy of vitamin D supplementation for preventing onset of

depressive disorders is unknown. Unclear cross-lagged associations Unknown dosing requirements

Efficacy of vitamin D supplementation for reducing depressive symptoms is largely unstudied

Thank you

Epilogue

Assessment of Publication Bias

Characteristics of cross-sectional studies of vitamin D and depression

Meta-analysis of cross-sectional studies of vitamin D deficiency and depression