Elsevier

Biological Psychiatry

Volume 74, Issue 12, 15 December 2013, Pages 872-878
Biological Psychiatry

Archival Report
Zinc in Depression: A Meta-Analysis

https://doi.org/10.1016/j.biopsych.2013.05.008Get rights and content

Background

Zinc is an essential micronutrient with diverse biological roles in cell growth, apoptosis and metabolism, and in the regulation of endocrine, immune, and neuronal functions implicated in the pathophysiology of depression. This study sought to quantitatively summarize the clinical data comparing peripheral blood zinc concentrations between depressed and nondepressed subjects.

Methods

PubMed, Cumulated Index to Nursing and Allied Health Literature, and PsycINFO were searched for original peer-reviewed studies (to June 2012) measuring zinc concentrations in serum or plasma from depressed subjects (identified by either screening or clinical criteria) and nondepressed control subjects. Mean (±SD) zinc concentrations were extracted, combined quantitatively in random-effects meta-analysis, and summarized as a weighted mean difference (WMD).

Results

Seventeen studies, measuring peripheral blood zinc concentrations in 1643 depressed and 804 control subjects, were included. Zinc concentrations were approximately −1.85 µmol/L lower in depressed subjects than control subjects (95% confidence interval: [CI]: −2.51 to −1.19 µmol/L, Z17 = 5.45, p < .00001). Heterogeneity was detected (χ217 = 142.81, p < .00001, I2 = 88%) and explored; in studies that quantified depressive symptoms, greater depression severity was associated with greater relative zinc deficiency (B = −1.503, t9 = −2.82, p = .026). Effect sizes were numerically larger in studies of inpatients (WMD −2.543, 95% CI: −3.522 to −1.564, Z9 = 5.09, p < .0001) versus community samples (WMD −.943, 95% CI: −1.563 to −.323, Z7 = 2.98, p = .003) and in studies of higher methodological quality (WMD −2.354, 95% CI: −2.901 to −1.807, Z7 = 8.43, p < .0001).

Conclusions

Depression is associated with a lower concentration of zinc in peripheral blood. The pathophysiological relationships between zinc status and depression, and the potential benefits of zinc supplementation in depressed patients, warrant further investigation.

Section snippets

Data Sources

Methodology was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (18). The MEDLINE, Embase, the Cochrane Collaboration, Allied and Complementary Medicine Database, and Cumulated Index to Nursing and Allied Health Literature were searched up to June 2012. A sample search strategy (for PubMed, National Library of Medicine) is detailed in Supplement 1. Reference lists of retrieved studies were searched for additional reports.

Study Selection

Inclusion criteria were:

Characteristics of Included Studies

Search criteria identified 299 unique records, of which 23 studies met inclusion criteria (Figure 1). Data could be extracted from 15 studies, and the authors of 2 additional studies provided means and SDs 14, 15. The characteristics of the included studies are summarized in Table 1. Of those studies, 10 reported on psychiatric inpatients, whereas 7 reported on community samples. The included studies ranged in sample size from 13 to 328, including a total of 1643 depressed patients and 804

Discussion

The present meta-analysis reports the concentration of zinc in the peripheral blood of depressed patients to be approximately 1.850 µmol/L lower than that of control subjects. Most of the included studies reported the means of depressed and control groups to be within normal laboratory reference ranges (i.e., 10.1–16.8 µmol/L) (35); however, the depressed group means were often near the lower boundary of the normal range.

Some variation in peripheral blood zinc concentrations might be explained

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