氯胺酮对情绪处理过程中大脑活动的影响：抑郁症患者与健康对照组参与者的差异发现。
Effects of Ketamine on Brain Activity During Emotional Processing: Differential Findings in Depressed Versus Healthy Control Participants.
机构信息
Section on Neurobiology and Treatment of Mood Disorders, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Section on Neurobiology and Treatment of Mood Disorders, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
出版信息
Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Jul;4(7):610-618. doi: 10.1016/j.bpsc.2019.01.005. Epub 2019 Jan 25.
BACKGROUND
In the search for novel treatments for depression, ketamine has emerged as a unique agent with rapid antidepressant effects. Experimental tasks involving emotional processing can be used during functional magnetic resonance imaging scanning to investigate ketamine's effects on brain function in major depressive disorder (MDD). This study examined ketamine's effects on functional magnetic resonance imaging activity during an emotional processing task.
METHODS
A total of 33 individuals with treatment-resistant MDD and 24 healthy control participants (HCs) took part in this double-blind, placebo-controlled crossover study. Participants received ketamine and placebo infusions 2 weeks apart, and functional magnetic resonance imaging scans were conducted at baseline and 2 days after each infusion. Blood oxygen level-dependent signal was measured during an emotional processing task, and a linear mixed-effects model was used to analyze differences in activation among group, drug, and task-specific factors.
RESULTS
A group-by-drug interaction was observed in several brain regions, including a right frontal cluster extending into the anterior cingulate cortex and insula. Participants with MDD had greater activity than HCs after placebo infusion but showed lower activity after ketamine infusion, which was similar to the activity in HCs after placebo. A group-by-drug-by-task condition interaction was also found, which showed further differences that varied between implicit and explicit emotional conditions.
CONCLUSIONS
The main results indicate that ketamine had differential effects on brain activity in participants with MDD versus HCs. The pattern of activation in participants with MDD after ketamine infusion resembled the activation in HCs after placebo infusion, suggesting a normalization of function during emotional processing. The findings contribute to a better understanding of ketamine's actions in the brain.
背景
在寻找治疗抑郁症的新方法时，氯胺酮作为一种具有快速抗抑郁作用的独特药物脱颖而出。在功能磁共振成像扫描期间，可以使用涉及情绪处理的实验任务来研究氯胺酮对重度抑郁症（MDD）患者大脑功能的影响。本研究考察了氯胺酮对情绪处理任务中功能磁共振成像活动的影响。
方法
共有 33 名治疗抵抗性 MDD 患者和 24 名健康对照者（HCs）参加了这项双盲、安慰剂对照交叉研究。参与者在 2 周内接受氯胺酮和安慰剂输注，在每次输注前后进行功能磁共振成像扫描。在情绪处理任务期间测量血氧水平依赖信号，并使用线性混合效应模型分析组间、药物间和任务特异性因素的激活差异。
结果
在几个脑区观察到组-药物相互作用，包括一个延伸到前扣带皮层和岛叶的右侧额区簇。与 HCs 相比，MDD 患者在接受安慰剂输注后表现出更大的活性，但在接受氯胺酮输注后表现出较低的活性，与 HCs 接受安慰剂后的活性相似。还发现了组-药物-任务条件的相互作用，进一步显示了在隐式和显式情绪条件之间存在差异。
结论
主要结果表明，氯胺酮对 MDD 患者和 HCs 的大脑活动具有不同的影响。MDD 患者在接受氯胺酮输注后的激活模式与 HCs 在接受安慰剂输注后的激活模式相似，表明在情绪处理过程中功能正常化。这些发现有助于更好地理解氯胺酮在大脑中的作用。
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