Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chiba, 260-8670, Japan.
Eur Arch Psychiatry Clin Neurosci. 2023 Oct;273(7):1513-1525. doi: 10.1007/s00406-023-01570-5. Epub 2023 Feb 14.
Cognitive impairment has been observed in patients with various psychiatric disorders, including schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD). Although modern therapeutic drugs can improve certain symptoms (i.e., psychosis, depression) in these patients, these drugs have not been found to improve cognitive impairment. The N-methyl-D-aspartate receptor antagonist (R,S)-ketamine has attracted attention as a rapidly acting antidepressant. In addition to its robust antidepressant effects, (R,S)-ketamine has been suggested to improve cognitive impairment in patients with MDD and BD, despite causing cognitive impairment in healthy control subjects. (R,S)-ketamine is a racemic mixture of equal amounts of (R)-ketamine (or arketamine) and (S)-ketamine (or esketamine). Arketamine has been found to have more potent antidepressant-like actions than esketamine in rodents. Interestingly, arketamine, but not esketamine, has been suggested to improve phencyclidine-induced cognitive deficits in mice. Furthermore, arketamine has been suggested to ameliorate cognitive deficits in rodent offspring after maternal immune activation. In the current article, it is proposed that arketamine has therapeutic potential for treating cognitive impairment in patients with psychiatric disorders. Additionally, the potential role of the gut-microbiome-brain axis in cognitive impairment in psychiatric disorders is discussed.
认知障碍在各种精神疾病患者中都有观察到,包括精神分裂症、重性抑郁障碍(MDD)和双相情感障碍(BD)。尽管现代治疗药物可以改善这些患者的某些症状(即精神病、抑郁症),但这些药物并未被发现可以改善认知障碍。N-甲基-D-天冬氨酸受体拮抗剂(R,S)-氯胺酮作为一种快速起效的抗抑郁药引起了关注。除了具有强大的抗抑郁作用外,(R,S)-氯胺酮被认为可以改善 MDD 和 BD 患者的认知障碍,尽管它会导致健康对照组的认知障碍。(R,S)-氯胺酮是(R)-氯胺酮(或 arketamine)和(S)-氯胺酮(或 esketamine)等量的外消旋混合物。在啮齿动物中,发现 arketamine 比 esketamine 具有更强的抗抑郁样作用。有趣的是,只有 arketamine,而不是 esketamine,被认为可以改善小鼠的苯环己哌啶诱导的认知缺陷。此外,arketamine 被认为可以改善母体免疫激活后啮齿动物后代的认知缺陷。在当前的文章中,提出 arketamine 有可能治疗精神疾病患者的认知障碍。此外,还讨论了肠道微生物群-大脑轴在精神疾病认知障碍中的潜在作用。