Increased inflammation predicts nine-year change in major depressive disorder diagnostic status.

Cytokine theory of depression proposes that increased baseline inflammatory activity may accumulate over time and lead to future major depressive disorder (MDD). However, most research conducted on this topic has been cross-sectional and examined between- (vs. within-) persons and symptom severity (vs. diagnosis). Therefore, we tested if elevated inflammatory activity at Time 1 (T1) would predict future within-person 9-year change in MDD diagnosis. Community-dwelling adults (n = 945) participated in the Midlife Development in the United States (MIDUS) study. T1 and Time 2 (T2) MDD status was assessed using the Composite International Diagnostic Interview-Short Form, and markers of inflammatory activity at T1 were measured (e.g., levels of serum interleukin-6 [IL-6], C-reactive protein [CRP], fibrinogen). Latent change score modeling was conducted. Higher T1 IL-6, CRP, and fibrinogen levels of inflammatory activity predicted T1-T2 development/relapse of MDD within persons. This effect occurred more strongly among women (vs. men; d = .149 vs. .042), younger (vs. older) adults (d = .137 vs. .119), persons with more (vs. less) chronic health issues (d = .133 vs. .065), low- (vs. middle- or high-) income earners (d = .161 vs. .050), and persons with more (vs. less) frequent childhood trauma (d = .156 vs. .017). Findings aligned with expanded cytokine theories, which posit that the impact of increased T1 inflammatory activity on future change in MDD status will be larger for subgroups vulnerable to increased stress exposure. Cognitive-behavioral or pharmacological approaches to reduce markers of inflammatory activity may prevent development/relapse of MDD. General Scientific Summary: Increased C-reactive protein (CRP), fibrinogen, and interleukin-6 (IL-6) levels predicted 9-year major depressive disorder (MDD) diagnostic status change more strongly in younger than older adults, women but not men, those with low (vs. high) income, as well as persons with high (vs. low) childhood trauma frequency and number of chronic illnesses. Findings aligned with expanded cytokine theories (e.g., social signal transduction theory of depression), which posit that markers of inflammatory activity predict future change in MDD status especially for populations vulnerable to heightened, chronic, and long-term exposure to environmental stressors. Continued efforts to empirically test expanded cytokine theories of depression may improve delineation of patterns of health disparities and facilitate effective measures to prevent the onset or recurrence of MDD. (PsycInfo Database Record (c) 2021 APA, all rights reserved).