HEALTH NEWS

Study Title:

Low LDL and Depression Risk in Elderly Men

Study Abstract

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.

From press release:

Most people know that high cholesterol levels place them at increased risk for heart disease and stroke. Prior research has shown that particular types of strokes contribute to one's risk for depression, and that abnormal blood lipid levels can increase the risk of depression in the elderly.

However, new findings by French researchers, published in Biological Psychiatry, suggest the link between increased cholesterol and depression may be complicated. They evaluated a large population of elderly men and women (aged 65 and over) over a seven year follow-up period, assessing them for symptoms of depression and measuring their lipid levels.

They found that, in women, depression was associated with low levels of the "good" form of cholesterol, high density lipoprotein (HDL). This disturbance in their cholesterol levels put them at higher risk for vascular disease, including stroke, by increasing their risk for developing lesions in their blood vessels called atherosclerotic plaques.

In contrast, the men who were at greater risk of depression had low levels of the "bad" form of cholesterol, low density lipoprotein (LDL). This was especially true for those men with a genetic vulnerability to depression related to a serotonin transporter gene.

This finding in men raises important considerations. Although this pattern of low LDL levels seemingly protects them from developing cardiovascular diseases or strokes, this study suggests that it increases their mental health risk at the same time.

Dr. Marie-Laure Ancelin, corresponding author for this study, commented: "Our results suggest that clinical management of abnormal lipid levels may reduce depression in the elderly, but different treatment will be required according to sex. LDL-C serum level seems to be an important biological marker in men, with a narrow range for normal functioning. Above this range, cardio- or cerebro-vascular risk increases and below it, there is increased risk of depression."

Therefore, the authors suggest that properly regulating the levels of HDL and LDL may help to prevent depression in the elderly. However, particularly careful management of LDL levels in men seems to be warranted. Dr. John Krystal, Editor of Biological Psychiatry, agreed, noting that "these new data provide yet another important reason that doctors and patients should monitor and regulate cholesterol levels carefully, through a combination of diet and medication."

Study Information

1.Marie-Laure Ancelin, Isabelle Carrière, Jean-Philippe Boulenger, Alain Malafosse, Robert Stewart, Jean-Paul Cristol, Karen Ritchie, Isabelle Chaudieu, Anne-Marie Dupuy
Gender and Genotype Modulation of the Association Between Lipid Levels and Depressive Symptomatology in Community-Dwelling Elderly (The ESPRIT Study)
Biological Psychiatry
2010 May
Institut de la Santé et de la Recherche Médicale (Inserm) and University of Montpellier 1, Hopital La Colombiere, Centre Hospitalier Universitaire (CHU), Montpellier, France