Antipsychotic drug effects on brain morphology in first-episode psychosis
Antipsychotic drug effects on brain morphology in first-episode psychosis
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DOI：
10.1001/archpsyc.62.4.361
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发表时间：
2005-04-01
影响因子：
--
通讯作者：
Tohen, M
中科院分区：
文献类型：
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作者：
Lieberman, JA;Tollefson, GD;Tohen, M
背景：早在精神分裂症首次发作时就发生的脑病理形态学改变已被广泛描述。纵向研究表明，这些变化可能是渐进的，并与临床结果相关。这就提出了抗精神病药物可能改变早期精神分裂症的这种病理形态学进展的可能性。目的：检验奥氮平治疗患者的全脑灰质体积和侧脑室体积随时间的变化小于氟哌啶醇治疗患者的先验假设，以及灰质和侧脑室体积的变化与精神病理学和神经认知的变化相关。设计：纵向、随机、对照、多中心、双盲研究。患者接受治疗并随访长达104周。在第0（基线）、12、24、52和104周进行神经认知和磁共振成像（MRI）评估。采用时间依赖性协变量的混合模型分析评估了治疗对MRI终点的影响，并探讨了MRI、精神病理学和神经认知结果之间的关系。（美国，11例;加拿大，1例;荷兰，1例;英格兰，1例）。参与者：首发精神病患者（DSM-IV）和健康志愿者。随机分配至常规抗精神病药氟哌啶醇组（2-20 mg/d），或非典型抗精神病药奥氮平（5-20 mg/d）。主要结果测量：通过MRI评估脑体积变化。在263例随机化患者中，161例接受了基线和至少1次基线后MRI评价。氟哌啶醇治疗的患者表现出灰质体积显著减少，而奥氮平治疗的患者则没有。一个匹配的健康志愿者（n = 58）同期检查的样本显示灰质volume.Conclusions没有变化：首发精神病患者表现出显着的治疗间差异MRI体积变化。氟哌啶醇与灰质体积的显著减少相关，而奥氮平与此无关。事后分析表明，对脑容量和精神分裂症的精神病理学的治疗效果可能相关。对脑形态的不同治疗效应可能是由于氟哌啶醇相关毒性或奥氮平的治疗效应更大。
Background: Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia.Objective: To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition.Design: Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes.Setting: Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1).Participants: Patients with first-episode psychosis (DSM-IV) and healthy volunteers.Interventions: Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d).Main Outcome Measures: Brain volume changes assessed by MRI.Results: Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume.Conclusions: Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.