Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial

Description: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have shown initial promise in producing antidepressant effects, possibly due to these drugs being peroxisome proliferator-activated receptor gamma (PPARγ) agonists. There is some, albeit mixed, evidence that PPARγ agonists have antidepressant effects in human and animal studies. This double-blind, placebo-controlled, pharmacologic functional magnetic resonance imaging (ph-fMRI) study was conducted to elucidate the impact of ibuprofen on emotion-related neural activity and whether observed effects were due to changes in PPARγ gene expression. Twenty healthy volunteers completed an emotional face matching task during three fMRI sessions, conducted one week apart. Placebo, 200 mg, or 600 mg ibuprofen was administered 1 h prior to each scan in a pseudo-randomized order, and whole blood samples were taken at each session to isolate PPARγ gene expression. Ibuprofen dose was associated with decreased blood oxygenation level dependent (BOLD) activation in the dorsolateral prefrontal cortex and fusiform gyrus. Additionally, PPARγ gene expression was associated with increased BOLD activation in the insula and transverse and superior temporal gyri. No interaction effects between ibuprofen dose and PPARγ gene expression on BOLD activation were observed. Therefore, results suggest that ibuprofen and PPARγ may have independent effects on emotional neurocircuitry. Future studies are needed to further delineate the roles of ibuprofen and PPARγ in exerting antidepressant effects in healthy as well as clinical populations (clinicaltrials.gov; Identifier: NCT02507219).

Related article: http://doi.org/10.1016/j.bbi.2021.05.023