Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Germany.
Eur Arch Psychiatry Clin Neurosci. 2012 Aug;262(5):403-14. doi: 10.1007/s00406-011-0281-8. Epub 2011 Dec 22.
The N-methyl-D-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. Administered to healthy individuals, a subanesthetic dose of the noncompetitive NMDAR antagonist ketamine reproduces several psychopathological symptoms commonly observed in patients with schizophrenia. In a counterbalanced, placebo-controlled, double-blind, within-participants study, fifteen healthy subjects were administered a continuous subanesthetic S-ketamine infusion while cortical activation was measured using functional magnetic resonance imaging. While being scanned, subjects performed an overt word generation task. Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine administration elicited effects on psychopathology, including difficulties in abstract thinking, lack of spontaneity and flow of conversation as well as formal thought disorder. On a behavioral level, verbal fluency performance was unaffected. The PANSS score for formal thought disorder positively correlated with activation measures encompassing the left superior temporal gyrus, the right middle and inferior frontal gyrus and the precuneus. Difficulty in abstract thinking was correlated with pronounced activations in prefrontal as well as in anterior cingulate regions, whereas hyperactivations in the left superior temporal gyrus were found in association with a lack of spontaneity and flow of conversation. In the absence of behavioral impairments during verbal fluency, NMDAR blocking evoked psychopathological symptoms and cortical activations in regions previously reported in schizophrenia patients. The results provide further support for the hypothesis of an NMDAR dysfunction in the pathophysiology of schizophrenia.
N-甲基-D-天冬氨酸受体（NMDAR）与精神分裂症的病理生理学有关。在健康个体中，给予亚麻醉剂量的非竞争性 NMDAR 拮抗剂氯胺酮可再现精神分裂症患者中常见的几种精神病理学症状。在一项平衡、安慰剂对照、双盲、内参与者研究中，十五名健康受试者接受了连续的亚麻醉 S-氯胺酮输注，同时使用功能磁共振成像测量皮质激活。在扫描过程中，受试者执行了显性单词生成任务。使用阳性和阴性综合征量表（PANSS）评估氯胺酮引起的精神病理学症状。氯胺酮给药引起了精神病理学效应，包括抽象思维困难、缺乏自发性和对话流畅性以及思维形式障碍。在行为水平上，言语流畅性表现不受影响。PANSS 思维形式障碍评分与包括左颞上回、右中回和下回以及楔前叶在内的激活测量值呈正相关。抽象思维困难与前额叶和前扣带区域的明显激活相关，而缺乏自发性和对话流畅性与左颞上回的过度激活相关。在言语流畅性测试中没有行为障碍的情况下，NMDAR 阻断引发了与精神分裂症患者先前报道的类似的精神病理学症状和皮质激活。这些结果进一步支持了 NMDAR 功能障碍在精神分裂症病理生理学中的假说。
