Kantrowitz Joshua T, Nolan Karen A, Epstein Michael L, Lehrfeld Nayla, Shope Constance, Petkova Eva, Javitt Daniel C
From the *Schizophrenia Research Center, Nathan Kline Institute, Orangeburg; †Department of Psychiatry, Columbia University; ‡Department of Psychiatry, New York University School of Medicine; §Graduate Center, City University of New York; and ∥Department of Child and Adolescent Psychiatry, New York University School of Medicine, New York, NY.
J Clin Psychopharmacol. 2017 Aug;37(4):447-451. doi: 10.1097/JCP.0000000000000722.
PURPOSE/BACKGROUND: Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist D-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport. This study investigates effects of bitopertin on NMDAR-related event-related potential deficits in schizophrenia.
METHODS/PROCEDURES: Patients with schizophrenia/schizoaffective disorder were treated with bitopertin (10 mg, n = 29), in a double-blind, parallel group investigation. Auditory mismatch negativity served as primary outcome measures. Secondary measures included clinical symptoms and neurocognitive performance.
FINDINGS/RESULTS: No significant changes were seen with bitopertin for neurophysiological, clinical, or neurocognitive assessments.
IMPLICATIONS/CONCLUSIONS: These findings represent the first assessment of the effect of bitopertin on neurophysiological biomarkers. Bitopertin did not significantly affect either symptoms or NMDAR-related biomarkers at the dose tested (10 mg). Mismatch negativity showed high test-retest reliability, supporting its use as a target engagement measure.
目的/背景：N-甲基-D-天冬氨酸受体（NMDAR）功能缺陷导致精神分裂症的症状和认知功能障碍，并与包括听觉失配负波在内的事件相关电位测量的生成受损有关。对NMDAR激动剂D-丝氨酸的平行研究表明，这些测量对基于谷氨酸的干预措施的敏感性与症状和认知反应有关。比特佩汀是一种甘氨酸转运的选择性抑制剂。本研究调查了比特佩汀对精神分裂症中与NMDAR相关的事件相关电位缺陷的影响。
方法/程序：在一项双盲平行组研究中，对精神分裂症/分裂情感性障碍患者使用比特佩汀（10毫克，n = 29）进行治疗。听觉失配负波作为主要结局指标。次要指标包括临床症状和神经认知表现。
在神经生理学、临床或神经认知评估方面，比特佩汀未显示出显著变化。
意义/结论：这些发现是对比特佩汀对神经生理学生物标志物影响的首次评估。在测试剂量（10毫克）下，比特佩汀对症状或与NMDAR相关的生物标志物均无显著影响。失配负波显示出较高的重测信度，支持其作为一种靶点参与度测量指标的应用。
