Prospect of Anti-Inflammatories in the Treatment and Prevention of Late-Life Depression

Ty Fields

Introduction. The link between inflammation and mental health disease has been an exciting development, prompting an outpouring of research analyzing the extent and nature of its involvement. While this link is most robustly understood and supported for depression, there are differences within sub-categories of depression that have yet to be addressed. For example, Late-Life depression (LLD) is a form of depression with similar symptomology to Major Depressive Disorder (MDD), but with a significantly lower remission rate.1 While there have been a multitude of studies exploring the pathological roles of inflammatory cytokines in MDD, research tailored to the same in LLD is lacking. Because of the disparity in remission rates between LLD and MDD, the objective of the current work is to understand the differences in symptomology as they relate to specific inflammatory biomarkers. It is the hope of this study to explore how current treatments effect inflammatory biomarkers, and the efficacy of anti-inflammatories in combination therapies for treatment-resistant patients. Methods. This review represents a compilation of 10 recent studies found through PubMed.  Results. Anti-depressants effective in precipitating remission in MDD were shown to exert anti-inflammatory effects by significantly lowering plasma levels of TNF-alpha, IL-6, IL-7, IL-8, IL-10, G-CSF and IFN-gamma.2 However, other inflammatory biomarkers associated with depressive symptoms were not significantly altered between remitted and treatment-resistant patients, such as IL-1Beta. Furthermore, a novel inflammatory biomarker unique to LLD, Neutrophil Gelatinase-Associated Ligand (NGAL), was implicated in production of the cognitive decline distinctive to LLD.3 NGAL concentration has been implicated in treatment resistance.3  Conclusion. Through this investigation, it has become apparent that anti-depressants do indeed carry anti-inflammatory properties2. Confirming this suggests that bolstering treatment with traditional or alternative anti-inflammatories could have efficacy. The discovery of the novel inflammatory marker, NGAL, and its correlation with cognitive decline in older patients, suggests that a possible next step is to develop therapeutics specific for the molecule. In addition, a clinical trial is scheduled to explore the efficacy of aspirin as a mono-therapy specifically in LLD4.  Using aspirin as a therapeutic in LLD would be an exciting step for public health, as this medication is affordable, available, used in treatment of other late-life diseases, and it would be the first time a therapeutic could be used to prevent mental health disease4.

 

  1. Comijs HC, Nieuwesteeg J, Kok R, et al. The two-year course of late-life depression; results from the Netherlands study of depression in older persons. BMC Psychiatry. 2015;15:20. doi:10.1186/s12888-015-0401-5.
  2. Johan Dahl a,*, Heidi Ormstad b, Hans Christian D. Aass c, Ulrik Fredrik Malt d,e, Lil Tra¨skman Bendz f, Leiv Sandvik g, Lena Brundin h,i, Ole A. Andreassen. The plasma levels of various cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocrinology , Volume 45 , 77 – 86
  3. Naudé PJ, den Boer JA, Comijs HC, Bosker FJ, Zuidersma M, Groenewold NA, De Deyn PP, Luiten PG, Eisel UL, Oude Voshaar RC. Sex-Specific Associations Between Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cognitive domains in late-life depression. Psychoneuroendocrinology. 2014 Oct;48:169-77. doi: 10.1016/j.psyneuen.2014.06.016. Epub 2014 Jun 27.
  4. Berk M, Woods RL, Nelson MR, Shah RC, Reid CM, Storey E, Fitzgerald SM, Lockery JE, Wolfe R, Mohebbi M, Murray AM, Kirpach B, Grim R, McNeil JJ. ASPREE-D: Aspirin for prevention of depression in the elderly. Int. Psychogeriatr. 2016 Oct;28(10):1741-8. Doi:10.1017/S104161021600079X