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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?

WHO. Mental Health Gap Action Programme: Scaling


Up Care for Mental, Neurological, and Substance Use
Disorders. WHO, 2008.

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

2N

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
N Engl J Med
2007;357:266-81

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
Chan
et al., 2011
May
et al. 2010
Milaneschi
et al., 2010

N
629

7358

639

Mean
age,
years Female
72.8

73.1

74.3

0%

58.8%

46.6%

Low
vitamin
D

Length
Definition
Type of
of
of low
vitamin D followvitamin D assessment
up

Site

GDS

5.2%

25(OH)D
<50 nmol/L

18.0%

25(OH)D
<37.4
nmol/L

CIA

1 year

USA

ICD-9 codes
via chart
review

31.0%

25(OH)D
<31.7
nmol/L

RIA

6 years

Italy

CES-D
16

RIA

4 years

Hong
Kong

Depression
measure/
definition
8

Abbreviations. 25(OH)D, 25-hydroxyvitamin D; nmol/L, nanomole/Liter; RIA, radioimmunoassay; CIA,


chemiluminescent immunoassay; GDS, Geriatric Depression Scale; ICD-9, International Classification of
Diseases9th edition; CES-D. Center for Epidemiologic StudiesDepression Scale.

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