Abstract：
BACKGROUND: Striatal hyperdopaminergia is implicated in the pathoetiology of schizophrenia, but how this relates to dopaminergic midbrain activity is unclear. Neuromelanin-sensitive MRI (NM-MRI) provides a marker of long-term dopamine function. We examined if midbrain NM-MRI contrast-to-noise ratio (NM-CNR) was higher in people with schizophrenia relative to controls and if this correlated with dopamine synthesis capacity.
METHODS: N=154 participants (n=74 individuals with schizophrenia and n=80 healthy controls) underwent NM-MRI of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n=38) also received [18F]-DOPA PET to measure dopamine synthesis capacity (Kicer) in the SN-VTA and striatum.
RESULTS: SN-VTA NM-CNR was significantly higher in patients with schizophrenia relative to controls (effect size=0.38, p=0.019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA Kicer positively correlated with SN-VTA NM-CNR (r=0.44, p=0.005) and striatal Kicer (r=0.71, p<0.001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal Kicer (r=0.53, p=0.005) and that this relationship appeared strongest between the ventral SN-VTA and associative striatum in schizophrenia.
CONCLUSIONS: Our results suggest that neuromelanin levels are higher in patients with schizophrenia relative to controls, particularly in midbrain regions that project to parts of the striatum which receive innervation from the limbic and association cortices. The direct relationship between measures of neuromelanin 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, potential therapeutic targets.
METHODS: N=154 participants (n=74 individuals with schizophrenia and n=80 healthy controls) underwent NM-MRI of the substantia nigra and ventral tegmental area (SN-VTA). A subset of the schizophrenia group (n=38) also received [18F]-DOPA PET to measure dopamine synthesis capacity (Kicer) in the SN-VTA and striatum.
RESULTS: SN-VTA NM-CNR was significantly higher in patients with schizophrenia relative to controls (effect size=0.38, p=0.019). This effect was greatest for voxels in the medial and ventral SN-VTA. In patients, SN-VTA Kicer positively correlated with SN-VTA NM-CNR (r=0.44, p=0.005) and striatal Kicer (r=0.71, p<0.001). Voxelwise analysis demonstrated that SN-VTA NM-CNR was positively associated with striatal Kicer (r=0.53, p=0.005) and that this relationship appeared strongest between the ventral SN-VTA and associative striatum in schizophrenia.
CONCLUSIONS: Our results suggest that neuromelanin levels are higher in patients with schizophrenia relative to controls, particularly in midbrain regions that project to parts of the striatum which receive innervation from the limbic and association cortices. The direct relationship between measures of neuromelanin 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, potential therapeutic targets.
摘要：
背景：纹状体高多巴胺与精神分裂症的病因学有关，但这与多巴胺能中脑活动的关系尚不清楚。神经黑色素敏感性MRI（NM-MRI）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-MRI对比噪声比（NM-CNR）是否高于对照组，以及这是否与多巴胺合成能力相关。
方法：N=154名参与者（n=74名精神分裂症患者和n=80名健康对照者）接受了黑质和腹侧被盖区（SN-VTA）的NM-MRI检查。精神分裂症组的一个子集（n=38）也接受了[18F]-DOPAPET来测量SN-VTA和纹状体中的多巴胺合成能力（Kicer）。
结果：精神分裂症患者的SN-VTANM-CNR明显高于对照组（效应大小=0.38，p=0.019）。对于内侧和腹侧SN-VTA中的体素，这种影响最大。在患者中，SN-VTAKicer与SN-VTANM-CNR（r=0.44，p=0.005）和纹状体Kicer（r=0.71，p<0.001）呈正相关。体素分析表明，SN-VTANM-CNR与纹状体Kicer呈正相关（r=0.53，p=0.005），并且这种关系在精神分裂症的腹侧SN-VTA与关联纹状体之间最强。
结论：我们的结果表明，精神分裂症患者的神经黑色素水平高于对照组，特别是在投射到纹状体部分的中脑区域，这些纹状体接受边缘和缔合皮质的神经支配。神经黑色素的测量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。我们的发现强调了特定的中纹状体回路作为精神分裂症多巴胺功能障碍的基因座，因此，潜在的治疗目标。
方法：N=154名参与者（n=74名精神分裂症患者和n=80名健康对照者）接受了黑质和腹侧被盖区（SN-VTA）的NM-MRI检查。精神分裂症组的一个子集（n=38）也接受了[18F]-DOPAPET来测量SN-VTA和纹状体中的多巴胺合成能力（Kicer）。
结果：精神分裂症患者的SN-VTANM-CNR明显高于对照组（效应大小=0.38，p=0.019）。对于内侧和腹侧SN-VTA中的体素，这种影响最大。在患者中，SN-VTAKicer与SN-VTANM-CNR（r=0.44，p=0.005）和纹状体Kicer（r=0.71，p<0.001）呈正相关。体素分析表明，SN-VTANM-CNR与纹状体Kicer呈正相关（r=0.53，p=0.005），并且这种关系在精神分裂症的腹侧SN-VTA与关联纹状体之间最强。
结论：我们的结果表明，精神分裂症患者的神经黑色素水平高于对照组，特别是在投射到纹状体部分的中脑区域，这些纹状体接受边缘和缔合皮质的神经支配。神经黑色素的测量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。我们的发现强调了特定的中纹状体回路作为精神分裂症多巴胺功能障碍的基因座，因此，潜在的治疗目标。
