Abnormalities in the inflammatory system are linked to many brain-based disorders, including but not limited to, MDD and bipolar disorder (BD). The impetus to consider inflammation as potentially relevant to the pathoetiology of domain-based psychopathology (eg, anhedonia) and/or mental disorders, is provided by a confluence of factors.
Many individuals who receive conventional treatments for mood disorders do not achieve/sustain symptom remission. Patient reports also indicate that among those who experience “clinically relevant improvement,” significant deficiencies and dissatisfaction with treatment remain, particularly as it relates to experiences in positive mental health, vitality, resiliency, and premorbid levels of function.
Support for research on inflammation in psychiatry comes from advances in the characterization of neurobiological alterations in individuals with brain-based disorders. The ability to identify and characterize genomic variants in large data sets using Genome-Wide Association Studies, as well as a fuller understanding of the role of microRNA. Finally, the Research Domain Criteria initiative of the NIH, has brought the field to the attention of common dimensions/domains of psychopathology regardless of DSM category.
Evidence implicates inflammation as a fundamental neurobiological alteration, thus targeting this system may provide beneficial effect on illness trajectory. Preliminary evidence indicates that some anti-inflammatory treatments are not only generally effective in mitigating dimensional psychopathology measures, but may have additional benefits on comorbidity that differentially affects individuals with mood disorders (eg, obesity).1
Dr. McIntyre reports that he is on the Speakers Bureau for AstraZeneca, Bristol-Myers Squibb, Janssen-Ortho, Eli Lilly, Lundbeck, Pfizer, Shire, Otsuka, Purdue, Takeda, and Allergan; he has received research support/grants from Stanley Medical Research Institute, National Alliance for Research on Schizophrenia and Depression (NARSAD), and National Institutes of Mental Health. Dr. Rong reports no conflicts of interest concerning the subject matter of this article.
1. Rosenblat JD, Kakar R, Berk M, et al. Anti-inflammatory agents in the treatment of bipolar depression: a systematic review and meta-analysis. Bipolar Dis. 2016;18:89-101.
2. Ragguett R-M, Cha DS, Subramaniapillai M, et al. Air pollution, aeroallergens and suicidality: a review of the effects of air pollution and aeroallergens on suicidal behavior and an exploration of possible mechanisms. Rev Environ Health. 2017;32:343-359.
3. Fernandes BS, Steiner J, Molendijk ML, et al. C-reactive protein concentrations across the mood spectrum in bipolar disorder: a systematic review and meta-analysis. Lancet Psychiatry. 2016;3:1147-1156.
4. Wikipedia. Julius Wagner-Jauregg. https://en.wikipedia.org/wiki/Julius_Wagner-Jauregg. Accessed February 22, 2018.
5. Papakostas GI, Shelton RC, Zajecka JM, et al. Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial. J Clin Psychiatry. 2014;75:855-863.
6. Rapaport MH, Nierenberg AA, Schettler PJ, et al. Inflammation as a predictive biomarker for response to Omega-3 fatty acids in major depressive disorder: a proof-of-concept study. Mol Psychiatry. 2016;21:71-79.
7. Machado-Vieira R, Gold PW, Luckenbaugh DA, et al. The role of adipokines in the rapid antidepressant effects of ketamine. Mol Psychiatry. 2017;22:127-133.
8. Schwieler L, Samuelsson M, Frye MA, et al. Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients. J Neuroinflam. 2016;13:51.
9. Wetherell JL, Hershey T, Hickman S, et al. Mindfulness-based stress reduction for older adults with stress disorders and neurocognitive difficulties: a randomized controlled trial. J Clin Psychiatry. 2017;78:e734-743.
10. Rosenblat JD, McIntyre RS. Efficacy and tolerability of minocycline for depression: a systematic review and meta-analysis of clinical trials. J Affect Disord. 2017;227:219-225.
11. Soczynska JK, Kennedy SH, Alsuwaidan M, et al. A pilot, open-label, 8-week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression. Bipolar Dis. 2017;19:198-213.
12. Mansur RB, Ahmed J, Cha DS, et al. Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: a pilot, open-label study. J Affect Dis. 2017;207:114-120.