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HDL cholesterol and the risk of depression over 5 years

Molecular Psychiatry volume 19, pages 637–638 (2014)Cite this article

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Abnormalities in lipid metabolism have been associated with prevalent depression and suicide behaviour, with low concentration of plasma high-density lipoprotein (HDL) cholesterol being consistently linked to depression.1 As most studies that have investigated this association have had a cross-sectional design, reverse causality and confounding could plausibly explain their findings. This prospective study sought to determine whether the plasma concentration of lipids, and more specifically of HDL cholesterol, was associated with increased risk of depression 5 years later, independent of cardiovascular diseases, diabetes, body mass, lifestyle factors and history of past depression.

These results revealed a reverse dose effect of HDL cholesterol on the 5-year risk of depression, which was particularly prominent in men with history of past depression. The plasma concentration of lipids declines in very old age,3 and this may negatively affect health.4 Data from the Whitehall II Study have implicated low HDL cholesterol in the decline of memory over 5 years,5 and preliminary evidence suggests that older people with low HDL cholesterol show a relative loss of cerebral grey matter volume compared with controls.6 These findings, together with those linking low HDL cholesterol to depression,1 suggest that lipid metabolism may have an important role in maintaining brain health.7 Kim and colleagues8 recruited 732 community-dwelling men and women aged 65 years or over for a study designed to assess the prevalence and 2-year incidence of dementia and depression in later life. In addition to measuring serum lipids, they extracted DNA to ascertain the serotonin gene-linked promoter region (5-HTTLPR). They found that low HDL cholesterol was associated with depression, but this association was only significant for participants carrying one or two copies of the s-allele of the 5-HTTLPR gene, which are associated with depression in the context of environmental adversity.9 One possible, albeit speculative, scenario would be that the brain has to handle increasing cumulative stress over time, which would decrease brain reserve and disrupt homeostatic systems. The ability of these systems to handle stress would be partly determined by susceptibility genes and partly by environmental factors, some of which would facilitate regeneration. One such factor could be HDL cholesterol.

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Authors and Affiliations

  1. School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia

    O P Almeida

  2. WA Centre for Health and Ageing of the Centre for Medical Research, University of Western Australia, Perth, WA, Australia

    O P Almeida & L Flicker

  3. Department of Psychiatry, Royal Perth Hospital, Perth, WA, Australia

    O P Almeida

  4. School of Medicine and Pharmacology of the University of Western Australia, Perth, WA, Australia

    B B Yeap, G J Hankey & L Flicker

  5. Department of Endocrinology, Fremantle Hospital, Fremantle, WA, Australia

    B B Yeap

  6. Department of Neurology, Royal Perth Hospital, Perth, Australia

    G J Hankey

  7. Queensland Research Centre for Peripheral Vascular Disease, School of Medicine and Dentistry of the James Cook University, Townsville, QLD, Australia

    J Golledge

  8. Department of Geriatric Medicine, Royal Perth Hospital, Perth, WA, Australia

    L Flicker

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  1. O P Almeida
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  2. B B Yeap
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  3. G J Hankey
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  5. L Flicker
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Corresponding author

Correspondence to O P Almeida.

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Almeida, O., Yeap, B., Hankey, G. et al. HDL cholesterol and the risk of depression over 5 years. Mol Psychiatry 19, 637–638 (2014). https://doi.org/10.1038/mp.2013.113

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