Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo-猫眼课题宝

DOI：

10.1038/s44220-023-00187-w

发表时间：

2024-01

期刊：

Nature. Mental Health

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Cynthia H. Y. Fu;Mathilde Antoniades;G. Erus;Jose A. Garcia;Yong Fan;Danilo Arnone;S. Arnott;Taolin Chen;K. S. Choi;Cherise R. Chin Fatt;B. N. Frey;V. Frokjaer;M. Ganz;Beata R. Godlewska;S. Hassel;K. Ho;Andrew M. McIntosh;Kun Qin;S. Rotzinger;M. Sacchet;J. Savitz;H. Shou;Ashish Singh;A. Stolicyn;Irina Strigo;S. Strother;D. Tosun;Teresa A. Victor;D. Wei;T. Wise;Roland Zahn;Ian M. Anderson;W. E. Craighead;J. Deakin;B. Dunlop;Rebecca Elliott;Qiyong Gong;I. Gotlib;C. Harmer;Sidney H. Kennedy;G. Knudsen;H. Mayberg;Martin P. Paulus;Jiang Qiu;Madhukar H. Trivedi;H. Whalley;Chao-Gan Yan;Allan H. Young;Christos Davatzikos

重性抑郁症（MDD）是一种异质性临床综合征，具有广泛的微妙神经解剖学相关性。我们的目的是确定神经解剖学的尺寸，其特点是抑郁症和预测治疗反应的选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药或安慰剂。在COCODINATE-MDD联盟中，共享了来自国际样本（N= 1，384）的原始MRI数据，这些样本来自当前抑郁发作（至少为中度）中首次发作和复发MDD（N= 685）的未用药个体，但不是难治性抑郁症，以及健康对照（N= 699）。MDD个体亚组（N= 359）的治疗反应前瞻性纵向数据可用。治疗为SSRI抗抑郁药物（艾司西酞普兰、西酞普兰、舍曲林）或安慰剂。协调多中心MRI数据，并利用HYDRONIC（一种半监督机器学习聚类算法）来识别与疾病相关的局部脑容量模式。MDD的最佳特征是两个神经解剖学维度，对安慰剂和SSRI抗抑郁药物表现出不同的治疗反应。维度1的特征在于保留的灰质和白色物质（N= 290 MDD），而维度2的特征在于相对于健康对照，灰质和白色物质（N= 395 MDD）广泛轻微减少。虽然在发病年龄、患病年数、发作次数或当前发作持续时间方面维度之间没有显著差异，但维度和治疗反应之间存在显著的相互作用效应。维度1显示SSRI药物治疗后抑郁症状显著改善（51.1%），但安慰剂治疗后变化有限（28.6%）。相比之下，维度2显示与SSRI（46.9%）或安慰剂（42.2%）相当的改善（β=-18.3，95%CI（-34.3至-2.3），P= 0.03）。这项病例对照研究的结果表明，基于神经成像的标记物可以帮助识别构成MDD的疾病维度并预测治疗反应。

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N= 1,384) of medication-free individuals with first-episode and recurrent MDD (N= 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N= 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N= 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N= 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N= 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (β= –18.3, 95% CI (–34.3 to –2.3),P= 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

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