Targeting the Organ-Brain Axis: The Modulatory Role of Peripheral Organs in Depression

Area of Science:

• Neuroscience
• Psychiatry
• Immunology

Background:

• Major Depressive Disorder (MDD) pathophysiology is not fully understood.
• Traditional view focuses on central nervous system (CNS) dysfunction.
• Emerging evidence suggests a brain-body framework involving peripheral abnormalities.

Purpose of the Study:

• Review communication pathways between peripheral organs and the brain.
• Explore the role of peripheral signals in MDD.
• Evaluate therapeutic strategies targeting peripheral systems.

Main Methods:

• Literature review of preclinical and clinical evidence.
• Analysis of neural, metabolic, immune, endocrine, and microbial pathways.
• Conceptual framework development for MDD phenotypes.

Main Results:

• Peripheral organs (gut, liver, heart, etc.) communicate with the brain.
• Peripheral signals may contribute to neuroinflammation and depressive phenotypes.
• Causal role in humans requires further investigation.

Conclusions:

• MDD may involve complex brain-body networks.
• Peripheral alterations can be contributors, correlates, or consequences of central states.
• Targeting peripheral systems offers potential therapeutic avenues with current limitations.