Clozapine for comorbid substance use disorder and schizophrenia: Do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine?
Clozapine for comorbid substance use disorder and schizophrenia: Do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine?
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DOI：
10.3109/10673229909017206
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发表时间：
1999-03-01
影响因子：
3.8
通讯作者：
Schildkraut, JJ
中科院分区：
文献类型：
--
作者：
Green, AI;Zimmet, SV;Schildkraut, JJ
酒精和其他滥用药物是精神分裂症患者普遍使用的药物，是导致精神障碍总体发病率的原因之一。标准或典型的抗精神病药物并不限制此类物质的使用，甚至可能使其更有可能发生。然而，来自我们小组和其他人的初步数据表明，非典型抗精神病药物氯氮平可能会减少该人群中的物质使用。虽然认识到物质使用可能会减少精神分裂症患者的阴性症状(包括锥体外系症状和锥体外系症状)，但我们假设，物质使用的生物学基础与继发于这些人中功能障碍的多巴胺介导的皮质边缘系神经元功能障碍的“奖赏缺乏综合征”有关。我们进一步认为，氯氮平对合并精神分裂症和物质使用障碍的患者的有益作用可能与其通过对多巴胺能神经元、5-羟色胺能神经元，特别是去甲肾上腺素能神经元的不同作用，改善中皮质和中边缘多巴胺能神经元投射的缺陷有关。
Alcohol and other drugs of abuse are commonly used by persons with schizophrenia and contribute to the overall morbidity of the disorder. Standard, or typical, antipsychotic drugs do not limit such substance use and may even render it more likely. However, preliminary data from our group and others suggest that the atypical antipsychotic clozapine may decrease substance use in this population. While recognizing the likelihood that substance use decreases negative symptoms las well as extrapyramidal symptoms) in persons with schizophrenia, we hypothesize that the biological basis of substance use relates to a "reward-deficiency syndrome" secondary to dysfunctional dopamine-mediated mesocorticolimbic neurons in these individuals. We further suggest that clozapine's beneficial effect in patients with comorbid schizophrenia and substance use disorders may relate to its presumed ability to ameliorate the deficits in both the mesocortical and mesolimbic dopaminergic neuronal projections through its various actions on dopaminergic, serotonergic, and particularly noradrenergic neurons.