Associations between Melatonin, Neuroinflammation, and Brain Alterations in Depression

Abstract

Pro-inflammatory systemic conditions that can cause neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder (MDD). A prominent feature of MDD is disruption of circadian rhythms, of which melatonin is considered a key moderator, and alterations in the melatonin system have been implicated in MDD. Melatonin is involved in immune system regulation and has been shown to possess anti-inflammatory properties in inflammatory conditions, through both immunological and non-immunological actions. Melatonin has been suggested as a highly cytoprotective and neuroprotective substance and shown to stimulate all stages of neuroplasticity in animal models. The ability of melatonin to suppress inflammatory responses through immunological and non-immunological actions, thus influencing neuroinflammation and neurotoxicity, along with subsequent alterations in brain regions that are implicated in depression, can be demonstrated by the antidepressant-like effects of melatonin. Further studies that investigate the associations between melatonin, immune markers, and alterations in the brain structure and function in patients with depression could identify potential MDD biomarkers.

Keywords: biomarker; major depressive disorder; melatonin; neuroinflammation.

Figure 1

Disruption of the melatonin system can exacerbate inflammatory conditions, which increase neurotoxic metabolites through the kynurenine pathway or directly exert neurotoxic effects on specific brain regions. Disruption of the melatonin system can also lead to oxidative stress and excitotoxicity, further contributing to neuroinflammation, as well as exerting direct neurotoxic effects. Neuroinflammation and subsequent alterations in brain regions involved in emotional regulation have been suggested as an underlying mechanism for the pathophysiology of major depressive disorder.