Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin (NM)-sensitive magnetic resonance imaging provides a marker of long-term dopamine function. We examined whether midbrain NM-sensitive magnetic resonance imaging contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia than in healthy control (HC) participants and whether this correlated with dopamine synthesis capacity. One hundred fifty-four participants (schizophrenia group: = 74, HC group: = 80) underwent NM-sensitive magnetic resonance imaging of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group ( = 38) also received [F]-DOPA positron emission tomography to measure dopamine synthesis capacity (K) in the SN-VTA and striatum. SN-VTA NM-CNR was significantly higher in patients with schizophrenia than in HC participants (effect size = 0.38, = .019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA K positively correlated with SN-VTA NM-CNR ( = 0.44, = .005) and striatal K ( = 0.71, < .001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal K ( = 0.53, = .005) and that this relationship seemed strongest between the ventral SN-VTA and associative striatum in schizophrenia. Our results suggest that NM levels are higher in patients with schizophrenia than in HC individuals, particularly in midbrain regions that project to parts of the striatum that receive innervation from the limbic and association cortices. The direct relationship between measures of NM and dopamine synthesis suggests that these aspects of schizophrenia pathophysiology are linked. Our findings highlight specific mesostriatal circuits as the loci of dopamine dysfunction in schizophrenia and thus as potential therapeutic targets.

中文翻译：

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精神分裂症中的中纹状体多巴胺能回路功能障碍：多模式神经黑色素敏感磁共振成像和 [18F]-DOPA 正电子发射断层扫描研究


纹状体多巴胺能亢进与精神分裂症的病理学有关，但其与多巴胺能中脑活动的关系尚不清楚。神经黑色素 (NM) 敏感磁共振成像提供了长期多巴胺功能的标记。我们检查了精神分裂症患者的中脑 NM 敏感磁共振成像对比噪声比 (NM-CNR) 是否高于健康对照 (HC) 参与者，以及这是否与多巴胺合成能力相关。 154 名参与者（精神分裂症组：= 74，HC 组：= 80）接受了黑质和腹侧被盖区（SN-VTA）的 NM 敏感磁共振成像。精神分裂症组的一个子集 (= 38) 还接受了 [F]-DOPA 正电子发射断层扫描，以测量 SN-VTA 和纹状体中的多巴胺合成能力 (K)。精神分裂症患者的 SN-VTA NM-CNR 显着高于 HC 参与者（效应大小 = 0.38, = .019）。这种效应对于内侧和腹侧 SN-VTA 的体素来说最为明显。在患者中，SN-VTA K 与 SN-VTA NM-CNR (= 0.44, = .005) 和纹状体 K (= 0.71, < .001) 呈正相关。体素分析表明，SN-VTA NM-CNR 与纹状体 K (= 0.53，= .005) 呈正相关，并且在精神分裂症中，腹侧 SN-VTA 和关联纹状体之间的这种关系似乎最强。我们的结果表明，精神分裂症患者的 NM 水平高于正常人，特别是在投射到纹状体部分、接受边缘皮质和联合皮质神经支配的中脑区域。 NM 测量值与多巴胺合成之间的直接关系表明，精神分裂症病理生理学的这些方面是相关的。 我们的研究结果强调了特定的中纹状体回路是精神分裂症多巴胺功能障碍的位点，因此是潜在的治疗靶点。