Faculty, Staff and Student Publications
Publication Date
9-1-2024
Journal
Molecular Psychiatry
Abstract
Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants. Many research endeavors have sought to identify ketamine's mechanism of action in mood disorders; while many studies have focused on ketamine's role in glutamatergic modulation, several studies have implicated its role in regulating neuroinflammation. The complement system is an important component of the innate immune response vital for synaptic plasticity. The complement system has been implicated in the pathophysiology of depression, and studies have shown increases in complement component 3 (C3) expression in the prefrontal cortex of suicidal individuals with depression. Given the role of the complement system in depression, ketamine and the complement system's abilities to modulate glutamatergic transmission, and our current understanding of ketamine's anti-inflammatory properties, there is reason to suspect a common link between the complement system and ketamine's mechanism of action. This review will summarize ketamine's anti- inflammatory roles in the periphery and central nervous system, with an emphasis on complement system regulation.
Keywords
Ketamine, Humans, Antidepressive Agents, Depressive Disorder, Major, Complement System Proteins, Animals, Neuroimmunomodulation, Prefrontal Cortex
DOI
10.1038/s41380-024-02507-7
PMID
38575806
PMCID
PMC11804209
PubMedCentral® Posted Date
2-7-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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Medical Sciences Commons, Mental and Social Health Commons, Psychiatry Commons, Psychiatry and Psychology Commons