Objective: To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties.
Methods: Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale.
Results: Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial variance explained by their interaction: 13% for IL-6 and 31% for TNF-α, whereas full models accounted for 18% and 40%, respectively. Although predicted cytokine levels were consistent across n-6:n-3 ratios with low depressive symptoms, higher n-6:n-3 ratios were associated with progressively elevated TNF-α and IL-6 levels as depressive symptoms increased. Higher levels of sIL-6r were associated with higher n-6:n-3 ratios. Six individuals who met the criteria for major depressive disorder had higher n-6:n-3 ratios and TNF-α, IL-6, and sIL-6r levels than those who did not meet the criteria; excluding these six individuals reduced the variance explained by the depressive symptoms and n-6:n-3 ratio interaction.
Conclusions: Diets with high n-6:n-3 PUFA ratios may enhance the risk for both depression and inflammatory diseases.
AA = arachidonic acid; BMI = body mass index; CES-D = Center for Epidemiological Studies Depression Scale; DHA = docosahexanoic acid; EPA = eicosapentaenoic acid; IL-6 = interleukin-6; sIL-6r = IL-6 soluble receptor; n-3 = omega-3; n-6 = omega-6; NF-κB = nuclear factor kappa B; PSQI = Pittsburgh Sleep Quality Index; PUFA = polyunsaturated fatty acid; TNF-α = tumor necrosis factor-α.
From the Departments of Psychiatry (J.K.K.-G.), Human Nutrition (M.A.B.), Ohio State University Center for Biostatistics (K.P., S.L.), Neurology (D.Q.B.), Ohio State University School of Public Health (S.L.), Molecular Virology, Immunology, and Medical Genetics (R.G.), Ohio State Institute for Behavioral Medicine Research (J.K.K.-G., S.L., R.G.); Ohio State University, Columbus, Ohio.
Address correspondence and reprint requests to Janice K. Kiecolt-Glaser, Department of Psychiatry, Ohio State University College of Medicine, 1670 Upham Drive, Columbus, OH 43210. E-mail: Kiecolt-Glaser.email@example.com
Received for publication July 18, 2006; revision received October 20, 2006.
The study was supported in part by Grant AG025732 from the National Institutes of Health, Grant MO1-RR-0034 from General Clinical Research Center, Grant CA16058 from Ohio State University Comprehensive Cancer Center Core, and funds from the Carol S. Kennedy endowment.