Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment
Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment
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DOI：
10.1038/npp.2015.90
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发表时间：
2015-09-01
影响因子：
7.6
通讯作者：
McDonald, Colm
中科院分区：
文献类型：
--
作者：
Ahmed, Mohamed;Cannon, Dara M.;McDonald, Colm
尽管有证据表明氯氮平可能具有神经保护作用，但很少有纵向磁共振成像（MRI）研究专门探讨氯氮平治疗精神分裂症的开始与局部脑容量或皮质厚度变化之间的关系。共有33名难治性精神分裂症患者和31名年龄和性别匹配的健康对照者在基线和开始服用氯氮平后6-9个月进行了结构MRI脑部扫描。使用SIENA（萎缩的结构图像评价，使用归一化）和FreeSurfer分析MRI图像，分别研究脑体积和皮质厚度随时间的变化。无论治疗反应如何，在患者组的右侧和左侧内侧前额叶皮质以及脑室周围区域中检测到显著更大的体积减少。与健康对照组相比，在患者中观察到广泛的进一步皮质变薄。在研究期间，大多数患者的脑功能和功能都有所改善，改善的患者更可能有较少的左内侧额叶皮质和右中颞叶皮质的皮质变薄。这些发现表明，在精神分裂症患者中，转换为氯氮平治疗的患者的脑体积和进行性皮质变薄正在减少。这种灰质丢失可能反映了一种与药物使用无关的进行性疾病过程，或者是由于转换为氯氮平治疗所致。大多数患者的临床改善表明，抗精神病药物相关的灰质体积损失可能不一定是有害的或反映神经毒性。
Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.