Brain, behavior, and immunity
July 1, 2025
Brandi Quintanilla, Dede Greenstein, Ashutosh Tripathi et al.
7 citations
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.
Brain, behavior, and immunity
April 4, 2025
Manivel Rengasamy, Benjamin Panny, Zakary Hutchinson et al.
3 citations
In adults with treatment-resistant depression, a single ketamine infusion did not produce detectable changes in blood markers of neurotrophic and inflammatory factors compared with a saline placebo, nor were those markers linked to depression improvement over five days. Among 133 participants, only one subgroup—those with a body-mass index below 25—showed an association: rising levels of interleukin-1 receptor antagonist in the first day after ketamine correlated with less reduction in depression symptoms. The results do not support the idea that peripheral neurotrophic or inflammatory factors mediate ketamine's rapid antidepressant effects, though central nervous system activity may still be involved.
Brain, behavior, and immunity
July 5, 2026
Bruno Pedraz-Petrozzi, Marta Marszalek-Grabska, Emilia Fornal et al.
In adults with treatment-resistant depression receiving six intravenous ketamine infusions over three weeks, higher baseline levels of the neuroprotective metabolite kynurenic acid (KYNA) in the kynurenine pathway were associated with greater symptom improvement by day 18. KYNA remained stable over time and did not track with symptom changes, suggesting it acts as a trait-like marker rather than a state-dependent one. Early shifts toward the neurotoxic branch of the pathway (kynurenine and 3-hydroxykynurenine) were linked to reductions in hopelessness and suicidality scores after the first infusion. These exploratory findings indicate that a kynurenine pathway profile biased toward neuroprotective metabolites may inform future biomarker studies of ketamine response, but require validation in larger samples.
Brain, behavior, and immunity
July 2, 2026
Samuel C Woodburn, Alexander M Kuhn, Kelly E Bosis et al.
Ketamine promotes spine growth on the apical dendrites of pyramidal neurons in the prefrontal cortex (PFC), and brain-derived neurotrophic factor (BDNF) signaling is critical for these effects. In mice, ketamine (10 mg/kg) reduced immobility in the forced swim test and increased dendritic spine density on PFC pyramidal neurons. These effects were associated with reduced microglia ramification and increased Bdnf expression in sorted PFC microglia. Mice with microglial Bdnf depletion (Cx3cr1Cre/+:Bdnffl/fl) showed decreased GluN2B levels in PFC synaptosomes, attenuated behavioral responses, and no change in dendritic spine density after ketamine. The results implicate microglia in the neurobiological and behavioral effects of ketamine.
Brain, behavior, and immunity
May 1, 2026
Havilah P Ravula, Barkha J Yadav-Samudrala, Laith E Sawaqed et al.
In a mouse model of HIV (Tg26 transgenic mice), chronic daily treatment with the cannabinoid THC for 90 days reduced the effects of a later high-dose THC challenge, particularly in females. Female mice with a history of chronic THC showed less THC-induced drop in body temperature, less pain relief, and less reduced movement after the acute high dose, and they also displayed more anxiety-like behavior on the elevated plus maze. HIV genotype influenced some of these effects. In the brain, chronic THC lowered levels of both pro- and anti-inflammatory cytokines in several regions of female mice, and HIV-positive mice showed increased microglial CCL3/MIP-1α co-occurrence in a sex- and brain-region-specific pattern.