Moderators of inflammation-related depression: a prospective study of breast cancer survivors

Abstract

Inflammation has been shown to predict depression, but sensitivity to inflammation varies across individuals. Experimental studies administering potent pro-inflammatory agents have begun to characterize this sensitivity. However, risk factors for inflammation-associated depression in naturalistic contexts have not been determined. The present study examined key psychological and behavioral risk factors (state anxiety, perceived stress, negative affect, disturbed sleep, and childhood adversity) as potential moderators of the relationship between inflammation and depressive symptoms in a prospective longitudinal study of breast cancer survivors. Women with early stage breast cancer were recruited after completing primary cancer treatment (n_final = 161). Depressive symptoms, inflammatory markers (CRP, IL-6, and sTNF-RII), and key risk factors were assessed post treatment (T1), at 6 and 12-month follow-ups (T2 and T3), and during a final follow-up (TF) 3-6 years after T1; childhood adversity was measured only at T3. Inflammatory markers were combined into a single inflammatory index prior to analyses. Women who reported higher levels of state anxiety, perceived stress, negative affect, and/or sleep disturbance at T1 (post-treatment) exhibited higher depressive symptoms at times when inflammation was higher than typical (interaction βs ranged from .06 to .08; all ps < .014). Results demonstrate the relevance of these risk factors for understanding inflammation-associated depression in a clinical context and could inform targeted strategies for prevention and treatment among at-risk populations.

Fig. 1. Study flow chart. A total of 161 participant contributed 544 (151 + 155 + 152 + 86) sampling occasions across the full study period.

It should be noted that some participants contributed valid level 1 observations at some time points but not others, and were still in analyses if they contributed at least 2 valid sampling occasions (e.g., missing T1 inflammation and depression data but valid data at T2 and T3). For this reason, the total number of level 2 units (161 participants) is greater than the total number of level 1 units (sampling occasions) at any given time point of the study (151, 155, 152, and 86).

Fig. 2. Predicted depressive symptom scores (at any given time) as a function of person-centered inflammation (at any given time) and T1 psychological risk factors (state anxiety, perceived stress, negative affect, and sleep disturbance).

Inflammation (as indexed by a composite measure of CRP, IL-6, and sTNF-RII) was positively associated with depressive symptoms at any given time among women who reported high levels of T1 anxiety, perceived stress, negative affect, and sleep disturbance. Predicted depressive symptom scores were adjusted for age, BMI, race, surgery, cancer stage, and receipt of chemotherapy, radiation therapy, and endocrine therapy. Shaded areas depict confidence intervals of simple slopes. The asterisk symbols (*) index statistically significant simple slopes (p < 0.05).