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Positron emission tomography imaging of serotonin degeneration and beta-amyloid deposition in late-life depression evaluated with multi-modal partial least squares
Translational Psychiatry ( IF 6.8 ) Pub Date : 2021-09-13 , DOI: 10.1038/s41398-021-01539-9
Gwenn S Smith 1, 2 , Clifford I Workman 1 , Hillary Protas 3 , Yi Su 3 , Alena Savonenko 4 , Hiroto Kuwabara 2 , Neda F Gould 1 , Michael Kraut 5 , Jin Hui Joo 1 , Ayon Nandi 2 , Dimitri Avramopoulos 6 , Eric M Reiman 3 , Kewei Chen 3
Affiliation  

Depression in late-life is associated with increased risk of cognitive decline and development of all-cause dementia. The neurobiology of late-life depression (LLD) may involve both neurochemical and neurodegenerative mechanisms that are common to depression and dementia. Transgenic amyloid mouse models show evidence of early degeneration of monoamine systems. Informed by these preclinical data, the hypotheses were tested that a spatial covariance pattern of higher beta-amyloid (Aβ) and lower serotonin transporter availability (5-HTT) in frontal, temporal, and parietal cortical regions would distinguish LLD patients from healthy controls and the expression of this pattern would be associated with greater depressive symptoms. Twenty un-medicated LLD patients who met DSM-V criteria for major depression and 20 healthy controls underwent PET imaging with radiotracers for Aβ ([11C]-PiB) and 5-HTT ([11C]-DASB). A voxel-based multi-modal partial least squares (mmPLS) algorithm was applied to the parametric PET images to determine the spatial covariance pattern between the two radiotracers. A spatial covariance pattern was identified, including higher Aβ in temporal, parietal and occipital cortices associated with lower 5-HTT in putamen, thalamus, amygdala, hippocampus and raphe nuclei (dorsal, medial and pontine), which distinguished LLD patients from controls. Greater expression of this pattern, reflected in summary 5-HTT/Aβ mmPLS subject scores, was associated with higher levels of depressive symptoms. The mmPLS method is a powerful approach to evaluate the synaptic changes associated with AD pathology. This spatial covariance pattern should be evaluated further to determine whether it represents a biological marker of antidepressant treatment response and/or cognitive decline in LLD patients.



中文翻译:

用多模态偏最小二乘法评估晚年抑郁症中血清素变性和β-淀粉样蛋白沉积的正电子发射断层扫描成像

晚年抑郁症与认知能力下降和全因痴呆的风险增加有关。晚年抑郁症(LLD)的神经生物学可能涉及抑郁症和痴呆症常见的神经化学和神经退行性机制。转基因淀粉样蛋白小鼠模型显示出单胺系统早期退化的证据。根据这些临床前数据,我们测试了以下假设:额叶、颞叶和顶叶皮质区域中较高的 β-淀粉样蛋白 (Aβ) 和较低的血清素转运蛋白可用性 (5-HTT) 的空间协方差模式可以将 LLD 患者与健康对照区分开来。这种模式的表达与更严重的抑郁症状有关。20 名符合 DSM-V 重性抑郁症标准的未接受药物治疗的 LLD 患者和 20 名健康对照者接受了使用 Aβ ([ 11 C]-PiB) 和 5-HTT ([ 11 C]-DASB) 放射性示踪剂的 PET 成像。基于体素的多模态偏最小二乘 (mmPLS) 算法应用于参数化 PET 图像,以确定两种放射性示踪剂之间的空间协方差模式。确定了空间协方差模式,包括颞叶、顶叶和枕叶皮质中较高的 Aβ 与壳核、丘脑、杏仁核、海马和中缝核(背侧、内侧和脑桥)中 5-HTT 较低相关,这将 LLD 患者与对照组区分开来。这种模式的较高表达(反映在 5-HTT/Aβ mmPLS 科目总分中)与较高水平的抑郁症状相关。mmPLS 方法是评估与 AD 病理相关的突触变化的有效方法。应进一步评估这种空间协方差模式,以确定它是否代表 LLD 患者抗抑郁治疗反应和/或认知能力下降的生物标志物。

更新日期:2021-09-13
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