Cortisol and C-reactive protein interact to predict depressive symptoms

A growing literature has sought to characterize the physiological correlates of depression, particularly with respect to inflammatory hypothalamic-pituitary-adrenal functioning and inflammation. These systems are intricately interrelated, but in relation to depression, have primarily been investigated independently. This study examined interactions between C-reactive protein (CRP), a widely studied inflammatory biomarker, and salivary cortisol in relation to depressive symptoms in a non-clinical sample of 18- to 25-year-olds. We analyzed data from 184 participants (M_age = 19.43 years, SD_age = 1.11, 59.8 % female) who provided dried blood spot and saliva samples, assayed for CRP and cortisol concentrations, respectively. Salivary cortisol was collected across the Trier Social Stress Task. Depressive symptoms were assessed with the Beck Depression Inventory. Covariate-adjusted linear regression models were used to test for main and interaction effects between cortisol and CRP on depressive symptoms. Controls included sex, age, parent income, race/ethnicity, BMI, and study site. In our sample, neither cortisol (b = -.01, SE b =.01, p = .17) nor CRP (b = -1.25, SE =.92, p = .18) were related to depressive symptom severity. However, there was a significant interaction effect (b =.04, SE b =.01, p = .001), such that cortisol reactivity was inversely related to depression among participants with low, but not moderate or high levels of CRP. Cortisol reactivity to moderate stressors appears to be beneficial, but our results suggest these benefits are attenuated by high inflammation. This indicates that inflammatory activity is an important contextual factor shaping the relationship between cortisol and depression, highlighting the utility of multi-system approaches to studying the physiological correlates of depression.