Thiebes Stephanie, Leicht Gregor, Curic Stjepan, Steinmann Saskia, Polomac Nenad, Andreou Christina, Eichler Iris, Eichler Lars, Zöllner Christian, Gallinat Jürgen, Hanganu-Opatz Ileana, Mulert Christoph
From the Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Thiebes, Leicht, Curic, Steinmann, Polomac, Andreou, Mulert); the Center for Gender Research and Early Detection, University of Basel Psychiatric Clinics, Basel, Switzerland (Andreou); the Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Eichler, Zöllner); the Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Gallinat); and the Developmental Neurophysiology, Institute of Neuroanatomy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Hanganu-Opatz).
J Psychiatry Neurosci. 2017 Jun;42(4):273-283. doi: 10.1503/jpn.160187.
Targeting the -methyl-D-aspartate receptor (NMDAR) is a major translational approach for treating negative symptoms of schizophrenia. Ketamine comprehensively produces schizophrenia-like symptoms, such as positive, cognitive and negative symptoms in healthy volunteers. The amplitude of the mismatch negativity (MMN) is known to be significantly reduced not only in patients with schizophrenia, but also in healthy controls receiving ketamine. Accordingly, it was the aim of the present study to investigate whether changes of MMN amplitudes during ketamine administration are associated with the emergence of schizophrenia-like negative symptoms in healthy volunteers.
We examined the impact of ketamine during an MMN paradigm with 64-channel electroencephalography (EEG) and assessed the psychopathological status using the Positive and Negative Syndrome Scale (PANSS) in healthy male volunteers using a single-blind, randomized, placebo-controlled crossover design. Low-resolution brain electromagnetic tomography was used for source localization.
Twenty-four men were included in our analysis. Significant reductions of MMN amplitudes and an increase in all PANSS scores were identified under the ketamine condition. Smaller MMN amplitudes were specifically associated with more pronounced negative symptoms. Source analysis of MMN generators indicated a significantly reduced current source density (CSD) under the ketamine condition in the primary auditory cortex, the posterior cingulate and the middle frontal gyrus.
The sample included only men within a tight age range of 20-32 years.
The MMN might represent a biomarker for negative symptoms in schizophrenia related to an insufficient NMDAR system and could be used to identify patients with schizophrenia with negative symptoms due to NMDAR dysfunction.
靶向N-甲基-D-天冬氨酸受体（NMDAR）是治疗精神分裂症阴性症状的一种主要转化方法。氯胺酮能在健康志愿者中全面诱发类似精神分裂症的症状，如阳性、认知和阴性症状。已知不仅精神分裂症患者，接受氯胺酮的健康对照者的失配负波（MMN）波幅也会显著降低。因此，本研究旨在调查氯胺酮给药期间MMN波幅的变化是否与健康志愿者中类似精神分裂症阴性症状的出现有关。
我们在MMN范式中使用64导脑电图（EEG）检查氯胺酮的影响，并使用阳性和阴性症状量表（PANSS）通过单盲、随机、安慰剂对照交叉设计评估健康男性志愿者的精神病理状态。使用低分辨率脑电磁断层扫描进行源定位。
24名男性纳入我们的分析。在氯胺酮条件下，MMN波幅显著降低，所有PANSS评分均升高。较小的MMN波幅与更明显的阴性症状具体相关。MMN发生器的源分析表明，在氯胺酮条件下，初级听觉皮层、后扣带回和额中回的电流源密度（CSD）显著降低。
样本仅包括年龄在20至32岁狭窄范围内的男性。
MMN可能代表与NMDAR系统不足相关的精神分裂症阴性症状的生物标志物，可用于识别因NMDAR功能障碍而出现阴性症状的精神分裂症患者。
