Depression and altered serum lipids in cynomolgus monkeys consuming a Western diet

Research over the past 15 years has suggested a high comorbidity of depression and coronary heart disease (CHD). However the mechanisms responsible for this relationship are poorly understood. This study was designed to examine the relationships between depressive behaviors and concentrations of circulating lipids and lipid signaling molecules that may be common to both CHD and depression in a cohort of cynomolgus monkeys (Macaca fascicularis) consuming a ‘Western’ diet, enriched with saturated fat and cholesterol. Socially-housed adult female cynomolgus monkeys (n = 36) were fed the Western diet for 27 months and depressive behavior was recorded weekly. Body weight, body mass index and circulating cholesterol profiles were measured in all animals, and fatty acids (FA) and FA-based signaling molecules were measured in the 6 least and 6 most depressed monkeys. Monkeys consuming the Western diet exhibited a broad range of percent time spent in depressive behavior. The percent time spent depressed was positively correlated with total plasma and LDL cholesterol and negatively correlated with HDL cholesterol. Despite being leaner, depressed monkeys had higher concentrations of monounsaturated fats (C16:1 and C17:1), a higher ω6/ω3 polyunsaturated fatty acid (PUFA) ratio and higher concentrations of omega-6 (ω6) PUFAs, particularly C18:2ω6 and C20:3ω6. FA ratios suggest that stearoyl CoA desaturase 1 activity was increased in depressed monkeys. Depressed female cynomolgus monkeys had elevated concentrations of serum lipids and lipid signaling molecules that are typically associated with obesity, insulin resistance and cardiovascular disease, which may account in part for the comorbidity of depression and CHD.

Research Highlights
► Monkeys consuming a Western diet may exhibit depressive behavior.
► Time spent depressed is correlated with plasma cholesterol concentrations.
► Depressed monkeys are leaner.
► Depressed monkeys have higher omega-6 fatty acids, and a higher omega 6:3 ratio.
► Stearoyl CoA desaturase 1 activity may be increased in depressed monkeys.
► These lipid metabolism characteristics are typical of obesity, diabetes, and CVD.