Ehrlich S, Yendiki A, Greve D N, Manoach D S, Ho B-C, White T, Schulz S C, Goff D C, Gollub R L, Holt D J
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
Psychol Med. 2012 Feb;42(2):267-82. doi: 10.1017/S003329171100119X. Epub 2011 Jul 7.
Previous studies have suggested that motivational aspects of executive functioning, which may be disrupted in schizophrenia patients with negative symptoms, are mediated in part by the striatum. Negative symptoms have been linked to impaired recruitment of both the striatum and the dorsolateral prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms are associated primarily with striatal dysfunction, using functional magnetic resonance imaging (fMRI).
Working-memory load-dependent activation and gray matter volumes of the striatum and DLPFC were measured using a region-of-interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls. In addition to testing for a linear relationships between striatal function and negative symptoms, we chose a second, categorical analytic strategy in which we compared three demographically and behaviorally matched subgroups: patients with a high burden of negative symptoms, patients with minimal negative symptoms, and healthy subjects.
There were no differences in striatal response magnitudes between schizophrenia patients and healthy controls, but right DLPFC activity was higher in patients than in controls. Negative symptoms were inversely associated with striatal, but not DLPFC, activity. In addition, patients with a high burden of negative symptoms exhibited significantly lower bilateral striatal, but not DLPFC, activation than schizophrenia patients with minimal negative symptoms. Working memory performance, antipsychotic exposure and changes in gray matter volumes did not account for these differences.
These data provide further evidence for a robust association between negative symptoms and diminished striatal activity. Future work will determine whether low striatal activity in schizophrenia patients could serve as a reliable biomarker for negative symptoms.
先前的研究表明，执行功能的动机方面可能在伴有阴性症状的精神分裂症患者中受到破坏，其部分由纹状体介导。阴性症状与纹状体和背外侧前额叶皮质（DLPFC）的募集受损有关。在此，我们使用功能磁共振成像（fMRI）测试了阴性症状主要与纹状体功能障碍相关的假设。
采用感兴趣区域（ROI）方法，测量了147例精神分裂症患者和160名健康对照者纹状体和DLPFC的工作记忆负荷依赖性激活及灰质体积。除了测试纹状体功能与阴性症状之间的线性关系外，我们还选择了第二种分类分析策略，即比较三个在人口统计学和行为学上匹配的亚组：阴性症状负担高的患者、阴性症状极少的患者和健康受试者。
精神分裂症患者与健康对照者之间纹状体反应幅度无差异，但患者右侧DLPFC活性高于对照者。阴性症状与纹状体活性呈负相关，但与DLPFC活性无关。此外，阴性症状负担高的患者双侧纹状体激活明显低于阴性症状极少的精神分裂症患者，但DLPFC激活无差异。工作记忆表现、抗精神病药物暴露及灰质体积变化不能解释这些差异。
这些数据为阴性症状与纹状体活动减弱之间的强烈关联提供了进一步证据。未来的研究将确定精神分裂症患者纹状体活动低是否可作为阴性症状的可靠生物标志物。
