Department of Radiology and Nuclear Medicine (van der Pluijm, Reijers, Tjong Tjin Joe, Booij, van de Giessen) and Department of Psychiatry (van der Pluijm, de Haan), Amsterdam UMC, University of Amsterdam, Amsterdam; Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical Center, New York (Wengler, Horga); Royal's Institute of Mental Health Research, University of Ottawa, Ottawa (Cassidy); Arkin Mental Health Care, Amsterdam (de Peuter).
Am J Psychiatry. 2024 Jun 1;181(6):512-519. doi: 10.1176/appi.ajp.20220780. Epub 2024 Mar 13.
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.
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.
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.
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.
需要寻找精神分裂症治疗抵抗的标志物，以减少有效治疗的延误。黑质纹状体多巴胺功能亢进在精神分裂症的病理中起着关键作用，但抗精神病药物无反应者并没有表现出多巴胺功能增加。神经黑色素敏感 MRI（NM-MRI），可以间接测量黑质中的多巴胺功能，具有作为无反应者的非侵入性标志物的潜力。NM-MRI 信号增加已在精神病中得到证实，但尚未在无反应者中进行评估。在这项研究中，作者研究了无反应者的 NM-MRI 信号是否低于有反应者。
对 79 例首发精神病患者和 20 例匹配的健康对照者进行 NM-MRI 扫描。在 6 个月的随访中评估治疗反应。在黑质内进行的预先设定的体素分析测试了 NM-MRI 信号与患者治疗反应之间的关系。
15 例患者被归类为无反应者，47 例患者为有反应者。17 例患者被排除在外，主要是因为药物不依从或诊断改变。体素分析显示，黑质腹侧层有 297 个显著体素与治疗反应呈负相关。无反应者和健康对照组的 NM-MRI 信号明显低于有反应者。受试者工作特征曲线分析显示，NM-MRI 信号将无反应者与曲线下面积在 0.62 到 0.85 之间区分开来。此外，患者的 NM-MRI 信号在 6 个月内没有变化。
这些发现为药物反应者和无反应者之间的多巴胺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一种临床应用标志物的潜力。
