Fijtman Adam, Yavi Mani, Vogeley Abigail, Greenstein Dede, Gilbert Jessica R, Zarate Carlos A
Section on the Neurobiology and Treatment of Mood Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA.
Bipolar Disord. 2025 Jun;27(4):316-322. doi: 10.1111/bdi.70027. Epub 2025 Apr 2.
Treatment-resistant depression (TRD) remains a challenge, necessitating novel interventions that address associated cognitive deficits. The glutamatergic modulator ketamine exerts rapid antidepressant effects, prompting investigators to assess its impact on cognitive function, specifically working memory. This study explored ketamine's influence on working memory and magnetoencephalography (MEG) patterns during a working memory task in individuals with TRD.
To examine the effects of ketamine on working memory, attention, and concentration, and to study MEG patterns during a working memory task in individuals with TRD.
Twenty-one individuals with TRD (14 with bipolar disorder, 7 with major depressive disorder) received ketamine and placebo infusions in a crossover trial. Behavioral and MEG data were collected at baseline and 6 to 9 h after ketamine and placebo (normal saline) infusion. Working memory, attention, and concentration were assessed with the N-back task.
Ketamine significantly improved depressive symptoms but had no effect on cognitive performance. MEG revealed increased gamma power in the parieto-occipital junction coupled with decreased gamma power in the posterior superior temporal sulcus and inferior frontal gyrus after ketamine administration compared to placebo.
Despite robust antidepressant effects, ketamine did not affect working memory, attention, or concentration. However, distinct gamma power changes in brain regions linked to attention and working memory highlight the need to further explore the neurobiological mechanisms underlying ketamine's cognitive effects in TRD. Future research with larger samples, broader cognitive batteries, and repeated ketamine infusions are needed to fully elucidate ketamine's cognitive effects in individuals with TRD.
难治性抑郁症（TRD）仍然是一个挑战，需要新的干预措施来解决相关的认知缺陷。谷氨酸能调节剂氯胺酮具有快速抗抑郁作用，促使研究人员评估其对认知功能的影响，特别是工作记忆。本研究探讨了氯胺酮对TRD患者在工作记忆任务期间的工作记忆和脑磁图（MEG）模式的影响。
研究氯胺酮对TRD患者工作记忆、注意力和专注力的影响，并研究其在工作记忆任务期间的MEG模式。
21名TRD患者（14名双相情感障碍患者，7名重度抑郁症患者）在交叉试验中接受氯胺酮和安慰剂输注。在基线以及氯胺酮和安慰剂（生理盐水）输注后6至9小时收集行为和MEG数据。使用n-back任务评估工作记忆、注意力和专注力。
氯胺酮显著改善了抑郁症状，但对认知表现没有影响。与安慰剂相比，MEG显示氯胺酮给药后顶枕交界处的γ功率增加，而后颞上沟和额下回的γ功率降低。
尽管氯胺酮具有强大的抗抑郁作用，但它并未影响工作记忆、注意力或专注力。然而，与注意力和工作记忆相关的脑区中γ功率的明显变化突出了进一步探索氯胺酮在TRD中的认知作用的神经生物学机制的必要性。未来需要进行更大样本、更广泛认知测试组以及重复氯胺酮输注的研究，以充分阐明氯胺酮对TRD患者的认知作用。
