Inflammatory profiles of severe treatment-resistant depression

J Affect Disord. 2019 Mar 1;246:42-51. doi: 10.1016/j.jad.2018.12.037. Epub 2018 Dec 17.


Background: Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients.

Methods: 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge.

Results: TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline.

Limitations: The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results.

Conclusions: However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.

Keywords: Cytokines; Inflammation; Treatment response; Treatment-resistant depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / therapeutic use
  • Biomarkers / blood
  • Case-Control Studies
  • Cytokines / blood*
  • Depressive Disorder, Treatment-Resistant / blood*
  • Depressive Disorder, Treatment-Resistant / drug therapy
  • Empirical Research
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Inflammation / blood*
  • Male
  • Middle Aged
  • Tumor Necrosis Factor-alpha


  • Antidepressive Agents
  • Biomarkers
  • Cytokines
  • Tumor Necrosis Factor-alpha