Pathophysiology of Neuropsychiatric Disorders Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Research and Development, Charlie Norwood VA Medical Center, Augusta, GA, USA. Electronic address: anilkumar.r.pillai@uth.tmc.edu.
2 papers in the library · 24 citations · publishing 2024-2025
Over 300 million people worldwide have major depressive disorder (MDD), but only 30-40% achieve remission with standard antidepressants. Ketamine offers rapid relief within hours, unlike weeks for conventional drugs. While many studies focus on ketamine's effects on glutamate, this review highlights its anti-inflammatory actions, especially through the complement system—a part of innate immunity involved in synaptic plasticity. The complement system is linked to depression, with increased complement component 3 (C3) expression found in the prefrontal cortex of suicidal individuals with depression. Given ketamine's anti-inflammatory properties and the complement system's role in glutamate modulation, the review suggests a common link between the complement system and ketamine's mechanism of action.
Ketamine, a rapid-acting antidepressant, may also regulate immune function. The complement system, part of the innate immune response involved in synaptic plasticity, has been linked to depression. This analysis of data from 39 people with major depressive disorder and 25 healthy volunteers, originally part of a randomized, double-blind trial comparing intravenous ketamine (0.5 mg/kg) to placebo, measured plasma levels of complement proteins C3a and C4a at baseline, 230 minutes, Day 1, and Day 3. A significant interaction between diagnosis and sex was found for C3a but not C4a levels. Ketamine's effects on C3a and C4a did not change over time. The findings suggest that targeting the complement pathway could lead to advances in treating major depressive disorder.