Depression's multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways

Area of Science:

• Neuroscience
• Immunology
• Psychiatry

Background:

• Depression, characterized by melancholic, anxiety, and fatigue/somatic symptoms, is increasingly understood as a biological process.
• Evidence links depression to peripheral cell-mediated activation, inflammation, and induction of oxidative and nitrosative stress (IO&NS) pathways.
• Central nervous system involvement includes microglial activation, decreased neurogenesis, and increased apoptosis.

Purpose of the Study:

• To explain the co-morbidities between depression and various brain and medical disorders.
• To identify common pathophysiological pathways underlying depression and associated conditions.
• To elucidate the role of IO&NS pathways in the manifestation and progression of depression.

Main Methods:

• Review of existing scientific literature and evidence.
• Analysis of shared biological pathways in depression and related disorders.
• Examination of the role of microglial activation and IO&NS pathways.

Main Results:

• A common denominator for depression and numerous brain/medical disorders is microglial activation and/or peripheral IO&NS pathway activation.
• Shared peripheral and/or central IO&NS pathways underpin the pathophysiology of depression and co-morbid conditions.
• IO&NS pathways act as a 'smoke sensor,' signaling threats via depressive symptoms.

Conclusions:

• Activation of peripheral and/or central IO&NS pathways explains the co-occurrence of depression with neurodegenerative, medical, and stress-related disorders.
• Depression is proposed to belong to the spectrum of inflammatory and degenerative disorders.
• Concomitant depression increases morbidity and mortality in medical disorders due to heightened inflammatory burden.