Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Mol Psychiatry. 2023 Apr;28(4):1770-1782. doi: 10.1038/s41380-023-01943-1. Epub 2023 Jan 19.
In multiple sclerosis (MS), gray matter (GM) atrophy progresses in a non-random manner, possibly in regions with a high distribution of specific neurotransmitters involved in several relevant central nervous system functions. We investigated the associations among regional GM atrophy, atlas-based neurotransmitter distributions and clinical manifestations in a large MS patients' group. Brain 3 T MRI scans, neurological examinations and neuropsychological evaluations were obtained from 286 MS patients and 172 healthy controls (HC). Spatial correlations among regional GM volume differences and atlas-based nuclear imaging-derived neurotransmitter maps, and their associations with MS clinical features were investigated using voxel-based morphometry and JuSpace toolbox. Compared to HC, MS patients showed widespread GM atrophy being spatially correlated with the majority of neurotransmitter maps (false discovery rate [FDR]-p ≤ 0.004). Patients with a disease duration ≥ 5 vs < 5 years had significant cortical, subcortical and cerebellar atrophy, being spatially correlated with a higher distribution of serotoninergic and dopaminergic receptors (FDR-p ≤ 0.03). Compared to mildly-disabled patients, those with Expanded Disability Status Scale ≥ 3.0 or ≥ 4.0 had significant cortical, subcortical and cerebellar atrophy being associated with serotonergic, dopaminergic, opioid and cholinergic maps (FDR-p ≤ 0.04). Cognitively impaired vs cognitively preserved patients had widespread GM atrophy being spatially associated with serotonergic, dopaminergic, noradrenergic, cholinergic and glutamatergic maps (FDR-p ≤ 0.04). Fatigued vs non-fatigued MS patients had significant cortical, subcortical and cerebellar atrophy, not associated with neurotransmitter maps. No significant association between GM atrophy and neurotransmitter maps was found for depression. Regional GM atrophy with specific neurotransmitter systems may explain part of MS clinical manifestations, including locomotor disability, cognitive impairment and fatigue.
在多发性硬化症（MS）中，灰质（GM）萎缩以非随机的方式进展，可能发生在涉及多个相关中枢神经系统功能的特定神经递质分布较高的区域。我们在一个大型 MS 患者群体中研究了区域 GM 萎缩、基于图谱的神经递质分布与临床表现之间的关联。从 286 名 MS 患者和 172 名健康对照者（HC）中获得了脑 3T MRI 扫描、神经学检查和神经心理学评估。使用基于体素的形态计量学和 JuSpace 工具包研究了区域 GM 体积差异与基于图谱的核成像衍生神经递质图谱之间的空间相关性，及其与 MS 临床特征的相关性。与 HC 相比，MS 患者表现出广泛的 GM 萎缩，与大多数神经递质图谱具有空间相关性（假发现率[FDR]-p≤0.004）。病程≥5 年与病程<5 年的患者表现出皮质、皮质下和小脑萎缩，与 5-羟色胺能和多巴胺能受体的更高分布具有空间相关性（FDR-p≤0.03）。与轻度残疾患者相比，扩展残疾状态量表≥3.0 或≥4.0 的患者表现出皮质、皮质下和小脑萎缩，与 5-羟色胺能、多巴胺能、阿片能和胆碱能图谱相关（FDR-p≤0.04）。认知障碍与认知正常的患者表现出广泛的 GM 萎缩，与 5-羟色胺能、多巴胺能、去甲肾上腺素能、胆碱能和谷氨酸能图谱具有空间相关性（FDR-p≤0.04）。疲劳与非疲劳的 MS 患者表现出皮质、皮质下和小脑萎缩，与神经递质图谱无关。GM 萎缩与神经递质图谱之间没有发现与抑郁相关的显著相关性。特定神经递质系统的区域 GM 萎缩可能解释了 MS 临床表现的一部分，包括运动障碍、认知障碍和疲劳。
