Abstract P248: Plasma Proteins Associated With Depressive Symptoms and Perceived Global Stress Among African American Adults in the Jackson Heart Study

Analyzing plasma proteins is a novel approach to uncover molecular mechanisms by which psychosocial stress may lead to chronic illness, including cardiometabolic disease. Proteomic analyses of cardiometabolic disease have been reported; however, proteomic studies of stress and depressive symptoms are limited. We hypothesized that plasma protein concentrations are both positively and negatively associated with greater depressive symptoms and perceived global stress, respectively, in African American adults from the Jackson Heart Study (JHS). Participants from exam 1 (2000-2004) with SomaScan 1.3k platform proteomics data were utilized (n=2143, mean age=55.3). Depressive symptoms and global stress scores were measured via the 20-item Centers for Epidemiological Studies (CES-D) Scale and an 8-item global perceived stress scale adapted for the JHS, respectively. Multivariable linear models were used to test the association between depressive symptoms and global stress scores and proteins, controlling for age, sex, and proteomics batch. Bonferroni correction was used to adjust the p-value threshold for multiple testing (3.78e-5, for 1,322 tested proteins). Six (6) proteins were found to be significantly associated with either depressive symptoms or perceived global stress. Angiopoietin-2 (β=0.014, SE=0.003, =1.33e-5), growth/differentiation factor 15 or MIC-1 (β=0.014, SE=0.003, p=7.08e-8), and kynureninase (β=0.014, SE=0.003, =1.55e-5) were positively associated with depressive symptoms. Contactin-5 (β=-0.017, SE=0.003, =1.40e-7) and neural cell adhesion molecule 1 (120 kDa isoform) (β=-0.016, SE=0.003, =6.74e-7) were negatively associated with depressive symptoms. Leukotriene A-4 hydrolase or LKHA4 (β=0.024, SE=0.005, =2.72e-6) was positively associated with perceived stress. We note that several of these proteins which are associated with higher levels of stress or depression symptoms have also been associated with cardiovascular disease and related phenotypes; for example, LKHA4 was the lead association with left ventricular mass in previous JHS analyses. JHS proteomic profiles revealed differences in protein concentrations by psychosocial measures. We will next explore the extent to which identified proteins may mediate relationships between stress and depressive symptoms and cardiovascular endpoints. Future investigations may identify potentially targetable proteomic mechanisms by which psychosocial stressors manifest into disease.

Duke Scholars

Author LaShaunta Glover Population Health Sciences