Increased Inflammation Predicts Nine-Year Change in Major Depressive Disorder Diagnostic Status

Nur Hani Zainal, Michelle G. Newman

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)829-840
Number of pages12
JournalJournal of abnormal psychology
Issue number8
StatePublished - 2021

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry


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