Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada.
J Affect Disord. 2021 Feb 15;281:61-66. doi: 10.1016/j.jad.2020.11.128. Epub 2020 Dec 3.
To explore the relationship between inflammation and neuronal metabolism in bipolar disorder (BD) by evaluating the neurochemical effects of the tumor necrosis factor-α (TNF-α) antagonist infliximab among individuals with bipolar depression METHODS: This is a post-hoc, exploratory analysis from a 12-week, randomized, double-blind, placebo-controlled trial with infliximab for adults with bipolar depression. We assessed the effects of infliximab on concentration of metabolites in the prefrontal cortex, using proton-magnetic resonance spectroscopy (H-MRS), as well as its association with clinical outcomes (i.e. depressive symptom severity and cognitive function).
Eighteen participants in the placebo and 15 in the infliximab group were included in this analysis. In the pre-specified primary outcome, there were no significant effects of treatment on prefrontal concentrations of N-acetylaspartate (NAA; p = 0.712). In the secondary analyses, there was a significant treatment by time interaction for glutamate (Glx; p = 0.018), indicating that Glx levels decreased in infliximab-treated patients, relative to placebo. Treatment group significantly moderated the association between changes in Glx levels and changes in a neurocognitive test (i.e. Digit Symbol Substitution Test; p = 0.014), indicating that in infliximab-treated participants reductions in Glx were associated with cognitive improvement.
Treatment with infliximab did not affect prefrontal NAA concentration in adults with BD. Exploratory analysis suggested a potential effect of treatment on the glutamate system, a finding that should be confirmed and validated by additional studies.
通过评估肿瘤坏死因子-α（TNF-α）拮抗剂英夫利昔单抗对双相情感障碍（BD）个体的神经化学影响，探讨炎症与神经元代谢之间的关系。
这是一项英夫利昔单抗治疗成人双相抑郁的 12 周、随机、双盲、安慰剂对照试验的事后探索性分析。我们使用质子磁共振波谱（H-MRS）评估英夫利昔单抗对前额叶皮质代谢物浓度的影响，并评估其与临床结局（即抑郁症状严重程度和认知功能）的关联。
本分析纳入了安慰剂组 18 名和英夫利昔单抗组 15 名参与者。在预先指定的主要结局中，治疗对前额叶 N-乙酰天冬氨酸（NAA；p=0.712）浓度没有显著影响。在次要分析中，谷氨酸（Glx；p=0.018）存在治疗与时间的交互作用，表明英夫利昔单抗治疗组患者的 Glx 水平降低，与安慰剂组相比。治疗组显著调节了 Glx 水平变化与神经认知测试（即数字符号替代测试；p=0.014）变化之间的关联，表明英夫利昔单抗治疗组参与者的 Glx 降低与认知改善相关。
英夫利昔单抗治疗对 BD 成人的前额叶 NAA 浓度没有影响。探索性分析表明治疗对谷氨酸系统可能有影响，这一发现需要通过其他研究进一步证实和验证。
