Cognitive Neuropsychology Laboratory, Monash Alfred Psychiatry Research Centre, Monash University School of Psychology and Psychiatry, Faculty of Medicine, Nursing and Health Sciences, Melbourne, Australia.
J Clin Psychopharmacol. 2011 Dec;31(6):690-7. doi: 10.1097/JCP.0b013e318234ee1e.
Semantic deficits constitute a core cognitive abnormality in schizophrenia. In the current study, the N-methyl-d-aspartate receptor antagonist ketamine was administered to healthy individuals acutely while they performed semantic processing tasks that included word pairs of differing degrees of semantic relatedness. Two dimensions of semantic processing were investigated: (1) explicit versus implicit processing, that is, unconscious versus conscious processing of semantic relationships and (2) direct versus indirect processing, that is, word pairs that are closely (LION-TIGER) or distantly (LION-STRIPES) related. The immediate effects of ketamine (0.8 mg/kg per hour during 80 minutes with approximate target plasma levels of 200 ng/mL) were examined in a placebo-controlled double-blind repeated-measures group design with 19 participants. It was predicted that ketamine would disrupt access to semantic memory as evidenced in schizophrenia, especially the indirectly related word pairs. In addition, implicit processing and explicit processing were predicted to be differentially affected. Ketamine administration did result in an abnormal performance in the reaction time responses to implicitly presented indirectly related word pairs (ie, greater priming) and reduced accuracy for explicit pairs. Performance on the directly related word pair tasks (both implicit and explicit) was similar across ketamine and placebo conditions, except for the suggestion of abnormal semantic matching in the accuracy data in the implicit task. This study confirms that implicit indirect semantic processing is changed under the influences of ketamine akin to schizophrenia. Future research comparing a schizophrenia group and a ketamine group directly about these tasks is needed to determine the similarity of impairments.
语义缺陷是精神分裂症的核心认知异常之一。在当前的研究中，我们给健康个体急性施用 N-甲基-D-天冬氨酸受体拮抗剂氯胺酮，同时让他们执行语义处理任务，包括语义关联程度不同的词对。我们研究了语义处理的两个维度：（1）显式与隐式处理，即对语义关系的无意识与有意识处理；（2）直接与间接处理，即紧密相关（狮子-老虎）或不那么紧密相关（狮子-条纹）的词对。在一项有 19 名参与者参与的安慰剂对照、双盲、重复测量组设计中，我们考察了氯胺酮（80 分钟内每小时 0.8 毫克/千克，目标血浆浓度约为 200 纳克/毫升）的即时效应。我们预测氯胺酮会像在精神分裂症中那样破坏语义记忆的获取，尤其是间接相关的词对。此外，我们预测隐式和显式处理会受到不同的影响。氯胺酮给药确实导致对隐式呈现的间接相关词对的反应时间反应异常（即更大的启动），并且对显式词对的准确性降低。在直接相关词对任务上（包括隐式和显式），氯胺酮和安慰剂条件下的表现相似，除了在隐式任务的准确性数据中暗示出异常的语义匹配。这项研究证实，隐式间接语义处理在氯胺酮的影响下发生改变，类似于精神分裂症。未来需要直接比较精神分裂症组和氯胺酮组在这些任务上的表现，以确定损伤的相似性。
