Abstract：
The role of cerebellar-cerebral functional connectivity (CC-FC) in obsessive-compulsive disorder (OCD), its trajectory post-pharmacotherapy, and its potential as a prognostic biomarker and genetic mechanism remain uncertain. To address these gaps, this study included 37 drug-naive OCD patients and 37 healthy controls (HCs). Participants underwent baseline functional magnetic resonance imaging (fMRI), followed by four weeks of paroxetine treatment for patients with OCD, and another fMRI scan post-treatment. We examined seed-based CC-FC differences between the patients and HCs, and pre- and post-treatment patients. Support vector regression (SVR) based on CC-FC was performed to predict treatment response. Correlation analysis explored associations between CC-FC and clinical features, as well as gene profiles. Compared to HCs, drug-naive OCD patients exhibited reduced CC-FC in executive, affective-limbic, and sensorimotor networks, with specific genetic profiles associated with altered CC-FC. Gene enrichment analyses highlighted the involvement of these genes in various biological processes, molecular functions, and pathways. Post-treatment, the patients showed partial clinical improvement and partial restoration of the previously decreased CC-FC. Abnormal CC-FC at baseline correlated negatively with compulsions severity and social functional impairment, while changes in CC-FC correlated with cognitive function changes post-treatment. CC-FC emerged as a potential predictor of symptom severity in patients following paroxetine treatment. This longitudinal resting-state fMRI study underscores the crucial role of CC-FC in the neuropsychological mechanisms of OCD and its pharmacological treatment. Transcriptome-neuroimaging spatial correlation analyses provide insight into the neurobiological mechanisms underlying OCD pathology. Furthermore, SVR analyses hold promise for advancing precision medicine approaches in treating patients with OCD.
摘要：
小脑-脑功能连接（CC-FC）在强迫症（OCD）中的作用，药物治疗后的轨迹，其作为预后生物标志物和遗传机制的潜力仍不确定。为了弥补这些差距,这项研究包括37例未接受药物治疗的强迫症患者和37例健康对照(HCs).参与者接受基线功能磁共振成像（fMRI），随后帕罗西汀治疗强迫症患者四周，和另一个fMRI扫描治疗后。我们检查了患者和HC之间基于种子的CC-FC差异，以及治疗前和治疗后的患者。基于CC-FC进行支持向量回归(SVR)以预测治疗反应。相关分析探讨CC-FC与临床特征之间的关联，以及基因图谱。与HC相比，未服用药物的强迫症患者在执行中表现出降低的CC-FC，情感边缘，和感觉运动网络，具有与改变的CC-FC相关的特定遗传特征。基因富集分析强调了这些基因参与各种生物过程，分子功能，和路径。后处理,患者表现出部分临床改善和部分恢复先前降低的CC-FC.基线CC-FC异常与强迫严重程度和社会功能损害呈负相关，而CC-FC的变化与治疗后的认知功能变化相关。CC-FC是帕罗西汀治疗后患者症状严重程度的潜在预测因子。这项纵向静息状态fMRI研究强调了CC-FC在OCD的神经心理学机制及其药物治疗中的关键作用。转录组-神经成像空间相关性分析提供了对OCD病理学基础的神经生物学机制的见解。此外，SVR分析有望促进治疗强迫症患者的精准医学方法。
