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Gender and Genotype Modulation of the Association Between Lipid Levels and Depressive Symptomatology in Community-Dwelling Elderly (The ESPRIT Study)

  • Marie-Laure Ancelin
    Correspondence
    Address correspondence to Marie-Laure Ancelin, Ph.D., Inserm U888, Hopital La Colombiere, pav 42, 39, Avenue C, Flahault, BP 34493, 34093 Montpellier CEDEX 5, France
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France
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  • Isabelle Carrière
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France
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  • Jean-Philippe Boulenger
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France

    Service de Psychiatrie Adulte, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France
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  • Alain Malafosse
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France

    University Hospital and School of Medicine of Geneva, University of Geneva, Switzerland
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  • Robert Stewart
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France

    Institute of Psychiatry, King's College London, London, United Kingdom
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  • Jean-Paul Cristol
    Affiliations
    Laboratoire de Biochimie, Hopital Lapeyronie, CHU, Montpellier, France
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  • Karen Ritchie
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France
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  • Isabelle Chaudieu
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France
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  • Anne-Marie Dupuy
    Affiliations
    Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France

    Laboratoire de Biochimie, Hopital Lapeyronie, CHU, Montpellier, France
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      Background

      Lipids appear to mediate depressive vulnerability in the elderly; however, sex differences and genetic vulnerability have not been taken into account in previous prospective studies.

      Methods

      Depression was assessed in a population of 1040 women and 752 men aged 65 years and older at baseline and after 7-year follow-up. Clinical level of depression (DEP) was defined as having either a score of 16 or higher on the Centre for Epidemiology Studies Depression scale or a diagnosis of current major depression on the Mini-International Neuropsychiatric Interview. Lipid levels, apolipoprotein E, and serotonin transporter linked promoter region (5-serotonin transporter gene linked promoter region) genotypes were evaluated at baseline.

      Results

      Multivariate analyses adjusted by sociodemographic and behavioral variables, measures of physical health including ischemic pathologies, and genetic vulnerability indicated gender-specific associations between dyslipidemia and DEP, independent of the use of lipid-lowering agents or apolipoprotein E status. Men with low low-density lipoprotein cholesterol levels had twice the risk of prevalent and incident DEP, whereas in women low high-density lipoprotein cholesterol levels were found to be significantly associated with increased prevalent DEP (odds ratio = 1.5) only. A significant interaction was observed between low low-density lipoprotein-cholesterol and 5-serotonin transporter gene linked promoter region genotype, men with s/s or s/l genotype being at increased risk of DEP (odds ratio = 6.0 and 2.7, respectively). No significant gene–environment interaction was observed for women.

      Conclusions

      DEP is associated with higher atherogenic risk in women (low high-density lipoprotein cholesterol), whereas the reverse is observed in men (low low-density lipoprotein cholesterol). Late-life depression may have a complex gender-specific etiology involving genetic vulnerability in men.

      Key Words

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