Objective:

Markers for treatment resistance in schizophrenia are needed to reduce delays in effective treatment. Nigrostriatal hyperdopaminergic function plays a critical role in the pathology of schizophrenia, yet antipsychotic nonresponders do not show increased dopamine function. Neuromelanin-sensitive MRI (NM-MRI), which indirectly measures dopamine function in the substantia nigra, has potential as a noninvasive marker for nonresponders. Increased NM-MRI signal has been shown in psychosis, but has not yet been assessed in nonresponders. In this study, the authors investigated whether nonresponders show lower NM-MRI signal than responders.

Methods:

NM-MRI scans were acquired in 79 patients with first-episode psychosis and 20 matched healthy control subjects. Treatment response was assessed at a 6-month follow-up. An a priori voxel-wise analysis within the substantia nigra tested the relation between NM-MRI signal and treatment response in patients.

Results:

Fifteen patients were classified as nonresponders and 47 patients as responders. Seventeen patients were excluded, primarily because of medication nonadherence or change in diagnosis. Voxel-wise analysis revealed 297 significant voxels in the ventral tier of the substantia nigra that were negatively associated with treatment response. Nonresponders and healthy control subjects had significantly lower NM-MRI signal than responders. Receiver operating characteristic curve analysis showed that NM-MRI signal separated nonresponders with areas under the curve between 0.62 and 0.85. In addition, NM-MRI signal in patients did not change over 6 months.

Conclusions:

These findings provide further evidence for dopaminergic differences between medication responders and nonresponders and support the potential of NM-MRI as a clinically applicable marker for treatment resistance in schizophrenia.

中文翻译：

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神经黑色素敏感 MRI 作为首发精神分裂症治疗抵抗的候选标志物

 客观的：

需要精神分裂症治疗抵抗的标志物来减少有效治疗的延误。黑质纹状体多巴胺能亢进功能在精神分裂症的病理学中起着关键作用，但抗精神病药物无反应者并未表现出多巴胺功能增加。神经黑色素敏感 MRI (NM-MRI) 可间接测量黑质中的多巴胺功能，有潜力作为无反应者的无创标记物。 NM-MRI 信号增加已在精神病中显示出来，但尚未在无反应者中进行评估。在这项研究中，作者调查了无反应者是否表现出比反应者更低的 NM-MRI 信号。

 方法：

对 79 名首发精神病患者和 20 名匹配的健康对照受试者进行了 NM-MRI 扫描。在 6 个月的随访中评估治疗反应。黑质内的先验体素分析测试了 NM-MRI 信号与患者治疗反应之间的关系。

 结果：

15 名患者被归类为无反应者，47 名患者被归类为有反应者。十七名患者被排除，主要是因为药物不依从或诊断改变。体素分析揭示了黑质腹侧层有 297 个与治疗反应呈负相关的显着体素。无反应者和健康对照受试者的 NM-MRI 信号明显低于反应者。受试者工作特征曲线分析显示，NM-MRI 信号将无应答者的曲线下面积介于 0.62 和 0.85 之间。此外，患者的 NM-MRI 信号在 6 个月内没有变化。

 结论：

这些发现为药物反应者和无反应者之间的多巴胺能差异提供了进一步的证据，并支持 NM-MRI 作为精神分裂症治疗抵抗的临床适用标记物的潜力。