Correspondence among gray matter atrophy and atlas-based neurotransmitter maps is clinically relevant in multiple sclerosis

被引:22
|
作者
Fiore, Alessia [1 ]
Preziosa, Paolo [1 ,2 ,3 ]
Tedone, Nicolo [1 ]
Margoni, Monica [1 ,2 ]
Vizzino, Carmen [1 ]
Mistri, Damiano [1 ]
Gueye, Mor [1 ,2 ]
Rocca, Maria A. [1 ,2 ,3 ]
Filippi, Massimo [1 ,2 ,3 ,4 ,5 ]
机构
[1] IRCCS San Raffaele Sci Inst, Div Neurosci, Neuroimaging Res Unit, Milan, Italy
[2] IRCCS San Raffaele Sci Inst, Neurol Unit, Milan, Italy
[3] Univ Vita Salute San Raffaele, Milan, Italy
[4] IRCCS San Raffaele Sci Inst, Neurorehabil Unit, Milan, Italy
[5] IRCCS San Raffaele Sci Inst, Neurophysiol Serv, Milan, Italy
关键词
AMINOBUTYRIC-ACID CONCENTRATION; BRAIN-DAMAGE; DISABILITY; DEPRESSION; FATIGUE; MECHANISMS; PATTERNS; SYSTEM; ABNORMALITIES; ASSOCIATION;
D O I
10.1038/s41380-023-01943-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1770 / 1782
页数:13
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