Stuke Heiner
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Berlin, Germany.
Front Psychiatry. 2023 Jan 9;13:1100030. doi: 10.3389/fpsyt.2022.1100030. eCollection 2022.
Recent clinical studies have shown that agonists at muscarinic acetylcholine receptors effectively reduce schizophrenia symptoms. It is thus conceivable that, for the first time, a second substance class of procholinergic antipsychotics could become established alongside the usual antidopaminergic antipsychotics. In addition, various basic science studies suggest that there may be a subgroup of schizophrenia in which hypofunction of muscarinic acetylcholine receptors is of etiological importance. This could represent a major opportunity for individualized treatment of schizophrenia if markers can be identified that predict response to procholinergic vs. antidopaminergic interventions. In this perspective, non-response to antidopaminergic antipsychotics, specific symptom patterns like visual hallucinations and strong disorganization, the presence of antimuscarinic antibodies, ERP markers such as mismatch negativity, and radiotracers are presented as possible markers of muscarinic deficit and thus potentially of response to procholinergic therapeutics. Finally, open questions and further research steps are outlined.
最近的临床研究表明，毒蕈碱型乙酰胆碱受体激动剂可有效减轻精神分裂症症状。因此可以设想，首次可能会有一种与常用的抗多巴胺能抗精神病药物并行的新型促胆碱能抗精神病药物问世。此外，多项基础科学研究表明，可能存在一个精神分裂症亚组，其中毒蕈碱型乙酰胆碱受体功能低下具有病因学意义。如果能够识别出预测对促胆碱能与抗多巴胺能干预反应的标志物，这可能为精神分裂症的个体化治疗带来重大机遇。从这个角度来看，对抗多巴胺能抗精神病药物无反应、视觉幻觉和严重紊乱等特定症状模式、抗毒蕈碱抗体的存在、失配负波等事件相关电位标志物以及放射性示踪剂，都被视为毒蕈碱缺乏的可能标志物，因此也可能是对促胆碱能治疗产生反应的潜在标志物。最后，概述了一些未解决的问题和进一步的研究步骤。
