PDF(Pubmed)
Abstract：
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.
摘要：
重度抑郁症（MDD）是一种异质性的临床综合征，具有广泛的细微的神经解剖学相关性。我们的目标是确定表征MDD的神经解剖学维度，并预测对选择性5-羟色胺再摄取抑制剂（SSRI）抗抑郁药或安慰剂的治疗反应。在COORDINATE-MDD联盟中，原始MRI数据来自国际样本（N=1,384），在目前至少中度抑郁发作的首次发作和复发性MDD（N=685）患者，但不是难治性抑郁症，以及健康对照（N=699）。关于治疗反应的前瞻性纵向数据可用于MDD个体的子集(N=359)。治疗是SSRI抗抑郁药(艾司西酞普兰，西酞普兰,舍曲林）或安慰剂。多中心MRI数据进行了协调，和九头蛇,半监督机器学习聚类算法，用于识别与疾病相关的区域大脑体积的模式。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的特征是保留的灰质和白质(N=290MDD)，而Dimension2的特征是相对于健康对照，灰质和白质（N=395MDD）普遍轻微减少。尽管发病年龄没有显着差异，多年的疾病，剧集的数量，或维度之间当前情节的持续时间，各维度与治疗反应之间存在显著的交互作用.维度1显示使用SSRI药物治疗后抑郁症状有显着改善（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，基于神经影像学的标志物可以帮助识别构成MDD的基于疾病的维度并预测治疗反应。
