Title:Therapeutic Strategies for Treatment of Inflammation-related Depression
Volume: 16
Issue: 2
Author(s): Miroslav Adzic*, Zeljka Brkic, Milos Mitic, Ester Francija, Milica J. Jovicic, Jelena Radulovic and Nadja P. Maric
Affiliation:
- Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, University of Belgrade,Serbia
Keywords:
Depression, inflammation, anti-inflammatory drugs, antidepressants, treatment, side effects.
Abstract: Background: Mounting evidence demonstrates enhanced systemic levels of inflammatory
mediators in depression, indicating that inflammation may play a role in the etiology and
course of mood disorders. Indeed, proinflammatory cytokines induce a behavioral state of conservation-
withdrawal resembling human depression, characterized by negative mood, fatigue, anhedonia,
psychomotor retardation, loss of appetite, and cognitive deficits. Neuroinflammation also contributes
to non-responsiveness to current antidepressant (AD) therapies. Namely, response to conventional
AD medications is associated with a decrease in inflammatory biomarkers, whereas resistance
to treatment is accompanied by increased inflammation.
Methods: In this review, we will discuss the utility and shortcomings of pharmacologic AD treatment
strategies focused on inflammatory pathways, applied alone or as an adjuvant component to
current AD therapies.
Results: Mechanisms of cytokine actions on behavior involve activation of inflammatory pathways
in the brain, resulting in changes of neurotransmitter metabolism, neuroendocrine function, and
neuronal plasticity. Selective serotonin reuptake inhibitors exhibit the most beneficial effects in
restraining the inflammation markers in depression. Different anti-inflammatory agents exhibit AD
effects via modulating neurotransmitter systems, neuroplasticity markers and glucocorticoid receptor
signaling. Anti-inflammatory add-on therapy in depression highlights such treatment as a candidate
for enhancement strategy in patients with moderate-to-severe depression.
Conclusion: The interactions between the immune system and CNS are not only involved in shaping
behavior, but also in responding to therapeutics. Even though, substantial evidence from animal
and human research support a beneficial effect of anti-inflammatory add-on therapy in depression,
further research with special attention on safety, particularly during prolonged periods of antiinflammatory
co-treatments, is required.
