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.
Brain, behavior, and immunity
April 1, 2025
Samantha M. Ayoub, Sunitha Vemuri, Elizabeth B. Hoang et al.
In a rat model of HIV, the psychoactive component of cannabis, THC, had opposite effects on different cognitive functions: it improved learning but worsened risk-based decision-making. HIV-transgenic rats and controls were tested on two tasks before and after acute and chronic THC injections. At baseline, HIV rats showed slower decision-making but intact cognition, suggesting early deficits. THC selectively altered performance in HIV rats, enhancing learning while impairing decision-making, effects not seen in controls. These findings mirror function-dependent cannabis effects observed in people with HIV and suggest THC may drive cannabis-induced cognitive changes in this population.
Brain, behavior, and immunity
October 1, 2024
Itay Ricon-Becker, Taylor N West, Barbara L. Fredrickson et al.
Baseline activity of the CREB transcription factor pathway, inferred from gene expression profiles in blood samples, predicted psychological responses to compassion-based meditation but not to mindfulness meditation. In two randomized controlled trials, individuals with higher pre-intervention CREB activity showed greater reductions in loneliness and negative emotions, and greater increases in life satisfaction, after compassion meditation. CREB activity was unrelated to baseline psychometric measures, suggesting that gene expression profiles may capture non-conscious psychobiological states that could help personalize intervention selection.
Brain, behavior, and immunity
October 1, 2023
Xinying Zhang, Teng He, Zifeng Wu et al.
In a mouse model of depression induced by lipopolysaccharide, CD38 expression increased in the hippocampus and cortex. Pharmacological inhibition or genetic knockout of CD38 reduced neuroinflammation, microglia activation, synaptic defects, and Sirt1/STAT3 signaling, and improved depression-like behaviors. Optogenetic activation of glutamatergic neurons in the hippocampal CA3 region reduced depression susceptibility and lowered CD38 expression. The antidepressant (R)-ketamine suppressed CD38 expression and reversed synaptic defects. Hippocampal CD38 is closely linked to depressive behaviors in this inflammation model, suggesting it as a potential therapeutic target.
Brain, behavior, and immunity
May 1, 2022
Emily K. Lindsay, J. D. Creswell, Harrison J. Stern et al.
Mindfulness training may boost immune responsivity in lonely older adults. In a trial of 190 adults aged 65–85, an 8-week Mindfulness-Based Stress Reduction program led to greater increases in stimulated interleukin-6 production—a marker of innate immune function—compared to a control health program. The effect was seen immediately after the intervention and persisted at a 3-month follow-up. No adverse events occurred. The findings suggest that mindfulness training could help counteract age- and stress-related declines in immunocompetence, potentially reducing infection risk and improving recovery.
Brain, behavior, and immunity
August 1, 2019
Laura Andrés-Rodríguez, Xavier Borràs, A. Feliu‐Soler et al.
Mindfulness-Based Stress Reduction (MBSR) reduced clinical severity in female fibromyalgia patients and prevented a decline in the anti-inflammatory cytokine IL-10 that occurred in the treatment-as-usual group. Higher baseline levels of the chemokine CXCL8 weakened MBSR's beneficial effects on pain, energy, stiffness, and sleep quality. Higher baseline ratios of pro-inflammatory IL-6/IL-10 and CXCL8/IL-10 were linked to less improvement in psychological inflexibility after MBSR. The authors propose that immune biomarkers may help predict who responds to MBSR.
Brain, behavior, and immunity
August 1, 2019
Linda Witek Janusek, Dina Tell, H. Mathews
Women newly diagnosed with early-stage breast cancer who participated in an 8-week mindfulness-based stress reduction (MBSR) program showed greater reductions in perceived stress, fatigue, sleep disturbance, and depressive symptoms compared to those in an active control condition of cancer recovery and health education classes. The MBSR group also exhibited faster restoration of natural killer cell activity, lower TNF-alpha and IL-6 levels, and greater IFN-gamma production over the study period. These results suggest that early MBSR provision benefits both psychological well-being and immune function relevant to cancer control.
Brain, behavior, and immunity
May 1, 2018
Quinn A Conklin, Brandon G King, Anthony P Zanesco et al.
Intensive meditation during a one-month residential Insight retreat was associated with an apparent increase in telomere length compared to a control group of experienced meditators not on retreat. Personality traits moderated this effect: retreat participants highest in neuroticism and lowest in agreeableness showed the greatest telomere length increases. Changes in telomere-related gene expression suggested improved telomere maintenance, including increases in Gar1 and HnRNPA1. No group-level changes in telomerase activity were observed, but retreat participants' telomerase activity at post-assessment was inversely related to retreat engagement and prior meditation experience. Neuroticism also predicted variation in telomerase activity across the retreat.
Brain, behavior, and immunity
January 23, 2017
A. Marsland, Dora C. H. Kuan, L. Sheu et al.
Plasma interleukin-6 (IL-6), an indicator of systemic inflammation, is associated with specific patterns of functional connectivity within the default mode network (DMN) of the brain. In 98 adults aged 30–54, higher IL-6 levels correlated with stronger connectivity in the sub-genual anterior cingulate cortex and weaker connectivity in the dorsal medial prefrontal cortex. These findings suggest a link between immune function and brain network activity that may relate to psychological and behavioral states in health and disease.
Brain, behavior, and immunity
August 1, 2013
Elizabeth A Hoge, Maxine M Chen, Esther Orr et al.
People who practice Loving-Kindness Meditation (LKM), a Buddhist-derived technique focusing on unselfish kindness toward all, tended to have longer telomeres—a cellular marker linked to slower aging—than non-meditators. In women, the difference was statistically significant even after accounting for body mass index and past depression. The study compared 15 LKM practitioners with 22 controls and found no significant differences in age, gender, race, education, or trauma exposure, though controls had higher BMI and lower rates of past depression. The results suggest LKM practice might influence telomere length, particularly in women, though the small sample size limits certainty.