Bartzokis George, Lu Po H, Nuechterlein Keith H, Gitlin Michael, Doi Clarissa, Edwards Nancy, Lieu Christopher, Altshuler Lori L, Mintz Jim
Department of Neurology, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1769, United States.
Schizophr Res. 2007 Jul;93(1-3):13-22. doi: 10.1016/j.schres.2007.02.011. Epub 2007 Apr 3.
Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination even in adulthood. Atypical antipsychotics have been shown to have a wide spectrum of efficacy across multiple psychiatric diseases and to be particularly efficacious in treatment resistant cases of disorders such as schizophrenia.
To test the a priori hypothesis that antipsychotic medications may differentially impact frontal lobe myelination in patients with schizophrenia.
DESIGN, SETTING, AND PARTICIPANTS: Participants ranged in age from 18-35 years, were all male, and were recruited by a single group of investigators using the same criteria. Two cohorts of subjects with schizophrenia early in their disease who were treated either with oral risperidone (Ris) or fluphenazine decanoate (Fd) were imaged in conjunction with cohorts of healthy controls. Each cohort was imaged using a different MRI instrument using identical imaging sequences.
MRI measures of frontal lobe white matter volume.
We estimated differences due to differences in the MRI instruments used in the two studies in the two healthy control groups matched to the patient samples, adjusting for age and other covariates. We then statistically removed those differences (which we assumed were due to instrument effects) from the data in the schizophrenia samples by subtraction. Relative to the differences seen in controls, the two groups of schizophrenic patients differed in their pattern of frontal lobe structure with the Ris-treated group having significantly larger white matter volume than the Fd group.
The results suggest that the choice of antipsychotic treatment may differentially impact brain myelination in adults with schizophrenia. Prospective studies are needed to confirm this finding. MRI can be used to dissect subtle differences in brain tissue characteristics and thus could help clarify the effect of pharmacologic treatments on neurodevelopmental and pathologic processes in vivo.
影像学和尸检研究提供了相互印证的证据，表明精神分裂症患者即使在成年期，额叶髓鞘形成的发育轨迹也存在失调。非典型抗精神病药物已被证明对多种精神疾病具有广泛的疗效，并且在精神分裂症等疾病的难治性病例中特别有效。
检验抗精神病药物可能对精神分裂症患者的额叶髓鞘形成产生不同影响这一先验假设。
设计、地点和参与者：参与者年龄在18至35岁之间，均为男性，由一组研究人员按照相同标准招募。两组处于疾病早期的精神分裂症患者，分别接受口服利培酮（Ris）或癸酸氟奋乃静（Fd）治疗，并与健康对照组一起接受成像。每个队列使用不同的MRI仪器，但成像序列相同。
额叶白质体积的MRI测量值。
我们在与患者样本匹配的两个健康对照组中，估计了两项研究中使用的MRI仪器差异所导致的差异，并对年龄和其他协变量进行了调整。然后，我们通过减法从精神分裂症样本的数据中统计去除这些差异（我们认为这是仪器效应所致）。相对于对照组的差异，两组精神分裂症患者的额叶结构模式不同，利培酮治疗组的白质体积明显大于癸酸氟奋乃静组。
结果表明，抗精神病治疗的选择可能对成年精神分裂症患者的脑髓鞘形成产生不同影响。需要进行前瞻性研究来证实这一发现。MRI可用于剖析脑组织特征的细微差异，从而有助于阐明药物治疗对体内神经发育和病理过程的影响。
