Dietary selenium and major depression: a nested case-control study

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Summary

Objectives and methods

Alterations in redox biology are established in depression; however, there are no prospective epidemiological data on redox-active selenium in depression. We aimed to determine if low levels of dietary selenium are associated with an increased risk for de novo major depressive disorder (MDD). In this nested case-control study, women aged 20 years or more were identified from a randomly selected cohort being followed prospectively for the Geelong Osteoporosis Study. Cases were individuals with incident MDD, identified using the Structured Clinical Interview for DSM-IV-TR (SCID-I/NP); controls had no such history. Dietary selenium intake was measured using a food frequency questionnaire at baseline, together with anthropometric and lifestyle measures.

Results

Eighteen women who developed de novo MDD were classified as cases; there were 298 controls. Low dietary selenium intakes increased the likelihood of developing MDD; OR 2.74 (95%CI 0.95–7.89). After adjusting for age and SES, compared with a high selenium intake, a low intake (<8.9 μg/MJ/day) was associated with an approximate trebling of the likelihood for developing de novo MDD; OR 2.95 (95%CI 1.00–8.72). Smoking, alcohol consumption and physical activity did not confound the association.

Conclusion

These data suggest that lower dietary selenium intakes are associated with an increased risk of subsequent de novo MDD. We propose that selenium's function as an antioxidant, and as a constituent of selenoproteins that are important in redox homeostasis, warrants further investigation as a risk factor for depression, and suggest a potentially novel modifiable factor in the primary prevention and management of depression.

Introduction

Selenium is an essential micronutrient in humans, although it is toxic in large doses.1 Selenium is incorporated into selenoproteins, major forms of which are the glutathione peroxidases and thioredoxin reductases. These are important antioxidants that reduce hydrogen peroxide to water, and reduce the damaging lipid hydroperoxides to alcohol.1, 2 Selenium inhibits the activation of NF-kappaB by modulating the expression of selenoprotein genes and suppressing C-reactive protein production, leading to attenuation of inflammation.3 Consequently, selenium may play a role in inflammatory disease, and might modulate clinical outcomes in infective and inflammatory illnesses.

Depression is becoming recognised as an inflammatory disorder, accompanied by an accumulation of highly reactive oxygen species that overwhelm usual defensive physiological processes.4, 5, 6, 7, 8, 9, 10, 11 Several indicators support a role for selenium in normal brain function. During times of selenium deficiency, there is preferential storage of selenium in the brain.12 Selenium has significant modulatory effects on dopamine13, 14, 15 and dopamine plays a role in the pathophysiology of depression and other psychiatric illnesses.16, 17 Diminished levels of selenium in the brain are associated with cognitive decline18 and Alzheimer's disease.19 Selenium supplementation has been linked with improvements in mood20, 21 and protection against postpartum depression.22

What is unclear is if low dietary selenium is a risk factor for the development of depression. In recognition of selenium's biological activity, we hypothesised that low levels of dietary selenium would be associated with an increased risk of major depressive disorder (MDD) in a representative population-based sample of women.

Section snippets

Study subjects

This study focuses on women enrolled in the Geelong Osteoporosis Study (GOS). A cohort of 1494 women was selected at random from the Commonwealth electoral rolls for the Barwon Statistical Division in south-eastern Australia, enrolled in the period 1994–1997 with 77.1% participation23 and followed prospectively for a decade. At baseline, selenium intakes were evaluated for 575 randomly selected women aged 20–89 years; 19 individuals who had anomalous responses on dietary questionnaires were

Results

The median selenium intake was 71.2 μg/day (interquartile range, IQR, 55.9–87.0). One hundred and one women (32.0%) had intakes below the Australian recommended daily intake of 60 μg/day; no toxic levels were found. There was a strong correlation between selenium intake and energy intake (both log transformed, r = 0.7, p < 0.001). Median selenium intake corrected for energy intake was 8.9 μg/MJ/day (IQR 7.7–10.5). Subject characteristics are shown for cases and controls in Table 1. No differences in

Discussion

Our results support the hypothesis that lower dietary selenium intakes increase the risk of subsequent de novo MDD. Selenium-rich foods include brazil nuts, kidneys, liver, fish and eggs; however, wheat products, fish, vegetables, beef and fruit provide most of the daily selenium intake among Australian women living in the study region.25 These findings are in accordance with previously published data showing that diets rich in wholefoods are associated with a reduced likelihood for depression

Conflict of interest statement

None of the other authors has any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.

Acknowledgements

The study was supported by the Victorian Health Promotion Foundation and the NHMRC (Australia).

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    The study was funded, in part, by the Victorian Health Promotion Foundation and the NHMRC, but they played no part in the design or conduct of the study; collection, analysis, and interpretation of the data; or in the writing of the manuscript or in the decision to submit the manuscript for publication. Felice Jacka and Sharon Brennan are supported by NHMRC Early Career Fellowships (628912 and 1012472, respectively). Michael Berk has received Grant/Research Support from the Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma, Servier and Astra Zeneca. He has been a paid consultant for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck and Pfizer and a paid speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Organon, Pfizer, Sanofi Synthelabo, Solvay and Wyeth.

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