Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial.
Impact of ibuprofen and peroxisome proliferator-activated receptor gamma on emotion-related neural activation: A randomized, placebo-controlled trial.
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DOI：
10.1016/j.bbi.2021.05.023
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Paulus MP
中科院分区：
文献类型：
--
作者：
Cosgrove KT;Kuplicki R;Savitz J;Burrows K;Simmons WK;Khalsa SS;Teague TK;Aupperle RL;Paulus MP
布洛芬等非甾体抗炎药 (NSAID) 已初步显示出产生抗抑郁作用的希望。这可能是因为这些药物除了抑制环氧合酶外，还是过氧化物酶体增殖物激活受体γ (PPARγ) 激动剂。一些证据（尽管好坏参半）表明 PPARγ 激动剂对人类和动物具有抗抑郁作用。这项双盲、安慰剂对照、药理学功能磁共振成像 (ph-fMRI) 研究旨在阐明布洛芬对情绪相关神经活动的影响，并确定观察到的影响是否是由于 PPARγ 基因表达的变化所致。 20 名健康志愿者在相隔一周的 3 次功能磁共振成像会议中完成了情感面部匹配任务。每次扫描前 1 小时以伪随机顺序给予安慰剂、200 mg 或 600 mg 布洛芬。每次收集外周血单核细胞以分离 PPARγ 基因表达的 RNA。在所使用的剂量下，布洛芬没有显着改变 PPARγ 基因表达。布洛芬剂量与情绪面部处理（面部形状）过程中背外侧前额皮质和梭状回的血氧水平依赖性（BOLD）激活减少有关。此外，PPARγ 基因表达与岛叶、横回和颞上回（面部形状）的 BOLD 激活增加相关。没有观察到布洛芬剂量和 PPARγ 基因表达对 BOLD 激活的相互作用影响。因此，结果表明布洛芬和 PPARγ 可能对情绪神经回路具有独立的影响。未来的研究需要进一步阐明布洛芬和 PPARγ 在健康和临床人群中发挥抗抑郁作用的作用。
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have shown initial promise in producing antidepressant effects. This is perhaps due to these drugs being peroxisome proliferator-activated receptor gamma (PPARγ) agonists, in addition to their inhibition of cyclooxygenase enzymes. Some, albeit mixed, evidence suggests that PPARγ agonists have antidepressant effects in humans and animals. This double-blind, placebo-controlled, pharmacologic functional magnetic resonance imaging (ph-fMRI) study aimed to elucidate the impact of ibuprofen on emotion-related neural activity and determine 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. Peripheral blood mononuclear cells were collected at each session to isolate RNA for PPARγ gene expression. At the doses used, ibuprofen did not significantly change PPARγ gene expression. Ibuprofen dose was associated with decreased blood oxygen level-dependent (BOLD) activation in the dorsolateral prefrontal cortex and fusiform gyrus during emotional face processing (faces-shapes). Additionally, PPARγ gene expression was associated with increased BOLD activation in the insula and transverse and superior temporal gyri (faces-shapes). No interaction effects between ibuprofen dose and PPARγ gene expression on BOLD activation were observed. Thus, 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.
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DOI：
10.1093/cercor/bhw157
发表时间：
2016-08
期刊：
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