Schizophrenia: Attention Deficits and the NMDA Hypothesis

精神分裂症：注意力缺損NMDA假說

藍先元(Hsien-Yuan Lane) ； 呂宗達(Tsung-Ta Lu) ； 張文和(Wen-Ho Chang)

《慈濟醫學雜誌》 15卷3期 (2003/06) Pp. 141-148

https://doi.org/10.6440/TZUCMJ.200306.0141

摘要

精神分裂症除了有活性與負性症狀，更有認知功能缺損，其中，注意力的缺損被認為是精神分裂症一種穩定的表現型(endophenotype)，且不隨症狀起伏或是藥物治療而有所變異。例如，Serotonin-dopamine antagonists(SDA)雖已被認為對於負性症狀與某些認知功能也所助益，但risperidone(目前許多國家最常用的SDA)卻與傳統抗精神病劑(主為dopamine antagonists)相若一皆對精神分裂症的注意力缺損無所增進。近年來，N-methyl-D-aspartate(NMDA)的功能低下被認為是精神分裂症(特別是認知缺損)的重要原因之ㄧ。最近更發現，健康志願者接受低於麻醉劑量的ketamine(一種NMDA的拮抗劑)除了會形成類似精神分裂症的活性與負性症狀，也會導致注意力的障礙。因此，精神分裂症的注意力缺損是否也與NMDA功能不足相關以及是否可以NMDA促進劑加以改善，直得探討。最近發現的若干人體內生性胺基酸(如D-serine或D-alanine)被認為具有NMDA促進劑之活性，然過去的小規模研究均以抗精神病劑無效的病患再加上這些NMDA促進劑以研究其療效，至於這些NMDA促進劑是否可做為精神分裂症單一治療之用藥、是否可改善注意力的缺損、以及血液藥物濃度與臨床反應之相關性則仍未被探討。最後，精神分裂症患者NMDA功能低下之機制亦有待未來的研究加以釐清。(慈濟醫學 2003; 15:141-148)

關鍵字

精神分裂症 ； 注意力的缺損

並列摘要

Schizophrenic patients reveal positive symptoms, negative symptoms, and cognitive impairment. Among them, attention deficit is considered one of the schizophrenic endophenotypes. Serotonin-dopamine antagonists (SDAs) are beneficial for positive and negative symptoms as well as certain cognitive deficits. However, neither risperidone (a commonly used SDA) nor typical antipsychotics improve attention in schizophrenic patients. Hypofunction of the N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. A recent study showed that sub-anesthetic doses of ketamine (an NMDA antagonist) could produce positive symptoms, negative symptoms, and attention deficits in healthy volunteers. Therefore, the relationship between NMDA hypofunction and impaired attention in schizophrenia deserves investigation. Pilot studies demonstrated adjunctive effects of NMDA-enhancing agents (e.g., D-serine and D-alanine, both endogenous amino acids) in certain schizophrenic patients who were concomitantly receiving other antipsychotics. Nonetheless, the attention (and other cognitive) effects and clinical responses of these agents (particularly as monotherapy) in the treatment of schizophrenia require further investigation. Furthermore, the mechanism of NMDA hypofunction in schizophrenia remains unclear. In the human brain, several proteins (including serine racemase, subunits of NMDA receptors, and others) could determine the NMDA's function; the impacts of their genetic variances on attention and other cognitive domains also warrant elucidation. (Tzu Chi Med J 2003; 15:141-148)

並列關鍵字

D-serine ； N-methyl-D-aspartate receptor ； schizophrenia ； attention deficit