Koola Maju Mathew
Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA.
Mol Neuropsychiatry. 2018 Oct;4(2):71-74. doi: 10.1159/000488797. Epub 2018 Jun 7.
Although first proposed in 1987, early diagnosis and intervention of psychotic disorders has only recently become a priority in the field. The interest in clinical high risk (CHR) for psychosis skyrocketed after attenuated psychosis syndrome (APS) was added to the DSM-5. There is evidence that in individuals with APS, attenuated mismatch negativity (MMN: functioning of the auditory sensory memory system) is a robust biomarker that can predict transition to psychosis. The underlying pathophysiological mechanism of MMN is via the interaction of -methyl-D-aspartate (NMDA) and alpha-7 nicotinic acetylcholine (α-7nACh) receptors. Galantamine is an acetylcholinesterase inhibitor and a positive allosteric modulator of the α-7nACh receptors. Memantine is an NMDA receptor antagonist. Memantine has been shown to enhance MMN in people with schizophrenia. Although no studies with galantamine have measured MMN, encenicline, an α-7 nicotinic partial agonist, increased MMN in people with schizophrenia. MMN has been suggested as a potential biomarker with the galantamine-memantine combination for the treatment of neuropsychiatric disorders. Hence, the galantamine-memantine combination may enhance MMN, thereby preventing CHR to psychosis. With no treatments available, randomized controlled trials are warranted with the galantamine-memantine combination to delay or prevent conversion to psychosis in individuals with CHR.
尽管精神病性障碍的早期诊断和干预早在1987年就已被提出,但直到最近才成为该领域的一个优先事项。在《精神疾病诊断与统计手册》第五版(DSM-5)中加入了亚临床精神病综合征(APS)后,对精神病临床高危(CHR)的关注度急剧上升。有证据表明,在患有APS的个体中,亚临床失配负波(MMN:听觉感觉记忆系统的功能)是一种可靠的生物标志物,可以预测向精神病的转变。MMN的潜在病理生理机制是通过N-甲基-D-天冬氨酸(NMDA)和α-7烟碱型乙酰胆碱(α-7nACh)受体的相互作用。加兰他敏是一种乙酰胆碱酯酶抑制剂,也是α-7nACh受体的正变构调节剂。美金刚是一种NMDA受体拮抗剂。美金刚已被证明可增强精神分裂症患者的MMN。虽然尚无关于加兰他敏的研究测量过MMN,但一种α-7烟碱型部分激动剂恩西尼cline可增加精神分裂症患者的MMN。MMN已被认为是加兰他敏-美金刚联合治疗神经精神疾病的一种潜在生物标志物。因此,加兰他敏-美金刚联合用药可能增强MMN,从而预防CHR发展为精神病。由于目前尚无有效治疗方法,有必要对加兰他敏-美金刚联合用药进行随机对照试验,以延缓或预防CHR个体发展为精神病。