Gender and genotype modulation of the association between lipid levels and depressive symptomatology in community-dwelling elderly (the ESPRIT study).
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.
Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France. marie-laure.ancelin@inserm.fr
Marie-Laure
ML
Ancelin
Isabelle
I
Carrière
Jean-Philippe
JP
Boulenger
Alain
A
Malafosse
Robert
R
Stewart
Jean-Paul
JP
Cristol
Karen
K
Ritchie
Isabelle
I
Chaudieu
Anne-Marie
AM
Dupuy
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood* / Q000235:genetics; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007406:Interview, Psychological; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012737:Sex Factors
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D050486:Serotonin Plasma Membrane Transport Proteins