Task-evoked substantia nigra hyperactivity associated with prefrontal hypofunction, prefrontonigral disconnectivity and nigrostriatal connectivity predicting psychosis severity in medication naïve first episode schizophrenia.
Task-evoked substantia nigra hyperactivity associated with prefrontal hypofunction, prefrontonigral disconnectivity and nigrostriatal connectivity predicting psychosis severity in medication naïve first episode schizophrenia.
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DOI：
10.1016/j.schres.2014.09.022
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发表时间：
2014-11
影响因子：
4.5
通讯作者：
Carter CS
中科院分区：
文献类型：
--
作者：
Yoon JH;Westphal AJ;Minzenberg MJ;Niendam T;Ragland JD;Lesh T;Solomon M;Carter CS
被广泛引用的前额叶功能障碍-过量皮质下多巴胺精神分裂症模型认为，前额叶功能障碍引起认知障碍和皮质下多巴胺释放的去抑制，这是精神病的基础。虽然这是最有影响力的精神分裂症模型之一，但只有少数研究提供了直接支持精神分裂症患者的证据。我们以前证明了任务诱发的黑质活动过度的背景下，前额叶功能减退和前额叶黑质功能障碍。此外，黑质纹状体功能连接被确定为精神病的潜在标志物。因为在先前的研究中，患者患有慢性精神分裂症，并接受抗精神病药物治疗，在本研究中，我们通过在首次发作（FE）的抗精神病药物初治（antipsychotic naïve）患者的独立样本中重现这些结果，来测试这些结果是否受到疾病慢性化和药物作用的混淆。我们在认知测试中比较了12名FE患者和15名人口统计学匹配的健康对照组的事件相关fMRI激活。我们发现黑质活动过度与前额叶功能减退和前额叶黑质功能性连接障碍有关，黑质纹状体功能性连接的程度与精神病的严重程度呈正相关。这项研究增加了支持精神分裂症前额叶-多巴胺模型的证据，并进一步验证了黑质纹状体功能连接作为精神病标志物的作用。
The widely cited prefrontal dysfunction – excess subcortical dopamine model of schizophrenia posits that prefrontal deficits give rise to cognitive impairments and the disinhibition of subcortical dopamine release underlying psychosis. While this has been one of the most influential schizophrenia models, only a handful of studies have provided evidence supporting it directly in patients with schizophrenia. We previously demonstrated task-evoked substantia nigra hyperactivity in the context of prefrontal hypofunction and prefrontonigral functional disconnectivity. In addition, nigrostriatal functional connectivity was identified as a potential marker of psychosis. Because patients in this prior study had chronic schizophrenia and were treated with antipsychotics, in the present study we tested whether these findings were confounded by illness chronicity and medication effects by seeking to reproduce these findings in an independent sample of antipsychotic naïve, first episode (FE) patients. We compared event-related fMRI activations from12 FE patients with 15 demographically matched healthy control subjects during cognitive testing. We found substantia nigra hyperactivity associated with prefrontal hypofunction and prefrontonigral functional disconnectivity, as well as the magnitude of nigrostriatal functional connectivity positively correlating with severity of psychosis. This study adds to the body of evidence supporting the prefrontal – dopamine model of schizophrenia and further validates nigrostriatal functional connectivity as a marker of psychosis.
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