A multimodal analysis of antipsychotic effects on brain structure and function in first-episode schizophrenia.
A multimodal analysis of antipsychotic effects on brain structure and function in first-episode schizophrenia.
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DOI：
10.1001/jamapsychiatry.2014.2178
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发表时间：
2015-03
期刊：
影响因子：
25.8
通讯作者：
Carter CS
中科院分区：
文献类型：
--
作者：
Lesh TA;Tanase C;Geib BR;Niendam TA;Yoon JH;Minzenberg MJ;Ragland JD;Solomon M;Carter CS
最近的数据表明，抗精神病药物治疗与精神分裂症患者皮质灰质减少有关。这些发现引起了人们对抗精神病药物治疗对大脑结构和功能的影响的关注;然而，迄今为止还没有研究直接测量精神分裂症患者的皮质功能，并显示抗精神病药物相关的灰质减少。在事件相关功能磁共振成像期间，使用皮质厚度测量和连续执行任务（AX-CPT）的AX版本管理，检查抗精神病药物对首发精神分裂症患者脑结构和功能的影响。这项病例对照横断面研究于2004年11月至2012年7月在加州大学戴维斯分校成像研究中心进行。参与者在入院时被招募到早期诊断和预防治疗诊所，这是一家专门治疗首发精神病的门诊诊所。接受非典型抗精神病药物治疗的首发精神分裂症患者（用药患者组）（n = 23）和未接受抗精神病药物治疗的患者（未用药患者组）（n = 22）以及健康对照参与者（n = 37）使用1.5-T扫描仪进行功能性磁共振成像。行为表现通过试验准确性、反应时间和d′-上下文得分来测量。体素统计参数图测试了AX-CPT期间功能活动的差异，皮质厚度的顶点图测试了整个大脑皮质厚度的差异。与对照组相比，用药患者组的前额叶（平均减少[MR]，0.27 mm; P <0.001）、颞叶（MR，0.34 mm; P = 0.02）、顶叶（MR，0.21 mm; P = 0.001）和枕叶（MR，0.24 mm; P = 0.001）皮质明显变薄。未用药的患者组在聚类校正后与对照组的皮质厚度无显著差异。与未用药患者组相比，用药患者组的背外侧前额叶皮质（DLPFC）（MR，0.26 mm; P = 0.001）和颞叶皮质（MR，0.33 mm; P = 0.047）的皮质更薄。在AX-CPT期间，与对照组相比，两个患者组均显示DLPFC活性降低（与给药组相比P = 0.02，与未给药组相比P <0.001）。然而，与未用药患者组相比，用药患者组表现出更高的DLPFC激活（P = 0.02）和更好的行为表现（P = 0.02）。这些发现强调了抗精神病药物治疗与精神分裂症中反复发现的结构、功能和行为缺陷之间的复杂关系。虽然短期抗精神病药物治疗与前额叶皮层变薄有关，但治疗也与更好的认知控制和前额叶功能活动增加有关。这项研究增加了重要的背景下，越来越多的文献抗精神病药物对大脑的影响，并建议谨慎解释神经解剖学的变化与脑功能的潜在不良影响。
Recent data suggest that treatment with antipsychotics is associated with reductions in cortical gray matter in patients with schizophrenia. These findings have led to concerns about the effect of antipsychotic treatment on brain structure and function; however, no studies to date have measured cortical function directly in individuals with schizophrenia and shown antipsychotic-related reductions of gray matter. To examine the effects of antipsychotics on brain structure and function in patients with first-episode schizophrenia, using cortical thickness measurements and administration of the AX version of the Continuous Performance Task (AX-CPT) during event-related functional magnetic resonance imaging. This case-control cross-sectional study was conducted at the Imaging Research Center of the University of California, Davis, from November 2004 through July 2012. Participants were recruited on admission into the Early Diagnosis and Preventive Treatment Clinic, an outpatient clinic specializing in first-episode psychosis. Patients with first-episode schizophrenia who received atypical antipsychotics (medicated patient group) (n = 23) and those who received no antipsychotics (unmedicated patient group) (n = 22) and healthy control participants (n = 37) underwent functional magnetic resonance imaging using a 1.5-T scanner. Behavioral performance was measured by trial accuracy, reaction time, and d′-context score. Voxelwise statistical parametric maps tested differences in functional activity during the AX-CPT, and vertexwise maps of cortical thickness tested differences in cortical thickness across the whole brain. Significant cortical thinning was identified in the medicated patient group relative to the control group in prefrontal (mean reduction [MR], 0.27 mm; P < .001), temporal (MR, 0.34 mm; P = .02), parietal (MR, 0.21 mm; P = .001), and occipital (MR, 0.24 mm; P = .001) cortices. The unmedicated patient group showed no significant cortical thickness differences from the control group after clusterwise correction. The medicated patient group showed thinner cortex compared with the unmedicated patient group in the dorsolateral prefrontal cortex (DLPFC) (MR, 0.26 mm; P = .001) and temporal cortex (MR, 0.33 mm; P = .047). During the AX-CPT, both patient groups showed reduced DLPFC activity compared with the control group (P = .02 compared with the medicated group and P < .001 compared with the unmedicated group). However, the medicated patient group demonstrated higher DLPFC activation (P = .02) and better behavioral performance (P = .02) than the unmedicated patient group. These findings highlight the complex relationship between antipsychotic treatment and the structural, functional, and behavioral deficits repeatedly identified in schizophrenia. Although short-term treatment with antipsychotics was associated with prefrontal cortical thinning, treatment was also associated with better cognitive control and increased prefrontal functional activity. This study adds important context to the growing literature on the effects of antipsychotics on the brain and suggests caution in interpreting neuroanatomical changes as being related to a potentially adverse effect on brain function.