Wilson James D, Gerlach Andrew R, Karim Helmet T, Aizenstein Howard J, Andreescu Carmen
Department of Mathematics and Statistics, University of San Francisco, San Francisco, CA, USA.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
Mol Psychiatry. 2023 Dec;28(12):5228-5236. doi: 10.1038/s41380-023-02158-0. Epub 2023 Jul 6.
The efficacy of antidepressant treatment in late-life is modest, a problem magnified by an aging population and increased prevalence of depression. Understanding the neurobiological mechanisms of treatment response in late-life depression (LLD) is imperative. Despite established sex differences in depression and neural circuits, sex differences associated with fMRI markers of antidepressant treatment response are underexplored. In this analysis, we assess the role of sex on the relationship of acute functional connectivity changes with treatment response in LLD. Resting state fMRI scans were collected at baseline and day one of SSRI/SNRI treatment for 80 LLD participants. One-day changes in functional connectivity (differential connectivity) were related to remission status after 12 weeks. Sex differences in differential connectivity profiles that distinguished remitters from non-remitters were assessed. A random forest classifier was used to predict the remission status with models containing various combinations of demographic, clinical, symptomatological, and connectivity measures. Model performance was assessed with area under the curve, and variable importance was assessed with permutation importance. The differential connectivity profile associated with remission status differed significantly by sex. We observed evidence for a difference in one-day connectivity changes between remitters and non-remitters in males but not females. Additionally, prediction of remission was significantly improved in male-only and female-only models over pooled models. Predictions of treatment outcome based on early changes in functional connectivity show marked differences between sexes and should be considered in future MR-based treatment decision-making algorithms.
抗抑郁治疗在老年期的疗效有限，而人口老龄化和抑郁症患病率上升使这一问题更加突出。了解老年期抑郁症（LLD）治疗反应的神经生物学机制势在必行。尽管抑郁症和神经回路中存在已确定的性别差异，但与抗抑郁治疗反应的功能磁共振成像（fMRI）标记相关的性别差异尚未得到充分研究。在这项分析中，我们评估了性别在LLD中急性功能连接变化与治疗反应关系中的作用。对80名LLD参与者在基线和SSRI/SNRI治疗第1天进行静息态fMRI扫描。功能连接的一天变化（差异连接）与12周后的缓解状态相关。评估了区分缓解者和未缓解者的差异连接图谱中的性别差异。使用随机森林分类器，通过包含人口统计学、临床、症状学和连接性测量的各种组合的模型来预测缓解状态。用曲线下面积评估模型性能，用排列重要性评估变量重要性。与缓解状态相关的差异连接图谱在性别上有显著差异。我们观察到男性缓解者和未缓解者之间一天连接变化存在差异的证据，而女性则没有。此外，仅男性和仅女性模型的缓解预测在合并模型的基础上有显著改善。基于功能连接早期变化的治疗结果预测显示出明显的性别差异，应在未来基于磁共振成像的治疗决策算法中予以考虑。
