Cortico-limbic volume abnormalities in late life depression are distinct from β amyloid and white matter pathologies

IF 9.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Psychiatry Pub Date : 2024-11-07 DOI:10.1038/s41380-024-02677-4
R. Scott Mackin, Emma Rhodes, Michelle Kassel, Maria Kryza-Lacombe, Emily Burns, David Bickford, Ruth Morin, Duygu Tosun, Susan Landau, Meryl A. Butters, Paul Aisen, Rema Raman, Andrew J. Saykin, Arthur Toga, Robert Koeppe, Clifford Jack, Michael W. Weiner, Craig Nelson, Philip S. Insel
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Abstract

This study was conducted to clarify patterns of cortico-limbic volume abnormalities in late life depression (LLD) relative to non-depressed (ND) adults matched for amyloid β (Aβ) deposition and to evaluate the relationship of volume abnormalities with cognitive performance. Participants included 116 LLD and 226 ND. Classification accuracy of LLD status was estimated using area under the receiver operator characteristic curve. Twenty-one percent of LLD and ND participants were Aβ positive and the groups did not differ on white matter hyperintensity volume (WMH (logscale); β = 0.12, p = 0.28). Compared to ND, the LLD group exhibited significantly lower bilateral volume in the lateral orbitofrontal cortex, hippocampus, accumbens area, superior temporal lobe, temporal pole, and amygdala after multiple comparison correction (p < 0.009 for all). Cortico-limbic volumes significantly improved classification of LLD beyond demographic characteristics, Aβ status, and WMH (AUCVol = 0.71, AUCWMH,  = 0.62, AUC difference, 0.09 [0.03 to 0.15]). LLD exhibited poorer performance on measures of global cognition, set shifting, and verbal learning and memory relative to ND. Cognitive function was positively associated with cortico-limbic volumes and these relationships did not differ by group. Secondary analyses with an ND sample additionally matched for Mild Cognitive Impairment (MCI) diagnosis showed a similar but attenuated pattern of volume abnormalities. Overall, our results support LLD as being associated with cortico-limbic volume abnormalities that are distinct from Aβ and white matter pathologies and that these volume abnormalities are important factors associated with cognitive dysfunction in LLD.

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晚年抑郁症的皮质-边缘体积异常有别于β淀粉样蛋白和白质病变
本研究旨在阐明晚期抑郁症(LLD)与淀粉样蛋白β(Aβ)沉积相匹配的非抑郁症(ND)成人皮质边缘体积异常的模式,并评估体积异常与认知能力的关系。参与者包括 116 名 LLD 和 226 名 ND。使用接收者操作特征曲线下面积估算了LLD状态分类的准确性。21%的 LLD 和 ND 参与者的 Aβ 呈阳性,两组在白质高密度体积(WMH(对数刻度);β = 0.12,p = 0.28)方面没有差异。与 ND 相比,经多重比较校正后,LLD 组的双侧眶额叶外侧皮层、海马、延脑区、颞上叶、颞极和杏仁核的体积均显著降低(均为 p < 0.009)。皮质-边缘体积显著改善了对 LLD 的分类,超越了人口统计学特征、Aβ 状态和 WMH(AUCVol = 0.71,AUCWMH,Aβ = 0.62,AUC 差异,0.09 [0.03 至 0.15])。与 ND 相比,LLD 在全局认知、集合转换以及言语学习和记忆方面的表现较差。认知功能与皮质-边缘体积呈正相关,这些关系在不同组别中并无差异。对与轻度认知功能障碍(MCI)诊断相匹配的 ND 样本进行的二次分析表明,体积异常的模式相似,但有所减弱。总之,我们的研究结果表明,LLD 与皮质-边缘体积异常有关,与 Aβ 和白质病变不同,这些体积异常是导致 LLD 认知功能障碍的重要因素。
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来源期刊
Molecular Psychiatry
Molecular Psychiatry 医学-精神病学
CiteScore
20.50
自引率
4.50%
发文量
459
审稿时长
4-8 weeks
期刊介绍: Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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