无法忍受不确定性与强迫症状严重程度的关联：小脑ALFF的中介作用

The Mediating Role of Cerebellar ALFF in the Association Between Intolerance of Uncertainty and Obsessive-Compulsive Symptom SeverityWang Shaoxia1, Zhang Xiang1, Lu Shihao1,Li Yuhan1, Song Fangqing1,Fang Jianqun2.

中文关键词:  强迫症  ALFF  小脑  无法忍受不确定性  中介效应

英文关键词:Obsessive-compulsive disorder  ALFF  Cerebellum  Intolerance of uncertainty  Mediation effect.

中文摘要:

      【摘要】背景 强迫症（OCD）致残负担高，无法忍受不确定性（IU）与强迫症状严重程度相关但其神经机制未明。小脑可能参与不确定性加工并在OCD患者中存在结构和功能的异常，但缺乏对其自发活动在IU与强迫症状关联中的直接证据。目的 探讨OCD患者小脑自发神经活动在IU与强迫症状之间的作用路径，为理解OCD的神经机制提供新的视角。方法 选取2022年11月—2024年11月在宁夏医科大学总医院心理卫生中心门诊就诊的、符合《国际疾病分类（第10版）》（ICD-10）OCD诊断标准的47例OCD患者以及40例同期社区招募的年龄性别与OCD匹配的对照者为研究对象。采集两组受试者的静息态功能磁共振成像数据，采用低频振幅（ALFF）分析方法比较两组全脑自发神经活动的差异；并使用耶鲁-布朗强迫量表（Y-BOCS）和简版无法忍受不确定性量表（IUS）进行临床评估。采用Pearson相关分析检验OCD患者各量表评分之间的相关性，进而以IU为自变量、强迫症状为因变量、组间差异脑区ALFF提取值为中介变量，使用SPSS24.0插件Process 4.0（模型4）检验差异脑区ALFF提取值在IU与强迫症状间的作用路径，采用Bootstrap进行中介效应检验。结果 共87例参与者完成研究并纳入统计分析。OCD组右侧小脑Crus II区的ALFF提取值较对照组降低（t=-5.254，FWE校正后P<0.01）。相关分析结果显示，OCD组右侧小脑Crus II区ALFF提取值与Y-BOCS总评分（r=-0.851）、强迫行为分量表评分（r=-0.647）、IUS总评分（r=-0.617）及预期性IU分量表评分（r=-0.717）均呈负相关（P均<0.01）；预期性IU分量表评分与Y-BOCS总评分（r=0.811）及强迫行为分量表评分（r=0.535）均呈正相关（P均<0.01）。中介效应分析显示，右侧小脑Crus II区ALFF提取值在预期性IU分量表评分对强迫行为分量表评分的影响中起部分中介作用，中介效应值为0.064，95% CI [0.004，0.136]，占总效应的24.57%。结论 OCD患者右侧小脑Crus II区自发神经活动降低，并与IU及强迫症状显著相关。该脑区在IU影响强迫行为中起部分中介作用，提示其可能参与OCD相关的神经机制。

英文摘要:

      【Abstract】Background Obsessive-compulsive disorder (OCD) carries a considerable disability burden. Intolerance of uncertainty (IU) is associated with OCD symptom severity, yet its neural underpinnings remain poorly understood. The cerebellum has been implicated in uncertainty processing and demonstrates structural and functional alterations in OCD; however, direct evidence regarding its spontaneous activity in mediating the IU–OCD symptom relationship remains lacking. Objective To explore the pathway through which spontaneous cerebellar neural activity may be involved in the association between intolerance of uncertainty and obsessive-compulsive symptoms in patients with OCD, with the aim of providing a new perspective for understanding the neural mechanisms of OCD. Methods A total of 47 patients with OCD who visited the Mental Health Center outpatient clinic of the General Hospital of Ningxia Medical University from November 2022 to November 2024 and met the diagnostic criteria for OCD according to the International Classification of Diseases, 10th Revision (ICD-10), together with 40 age- and sex-matched controls recruited from the community during the same period, were enrolled. Resting-state functional magnetic resonance imaging data were collected from all participants. Amplitude of low-frequency fluctuation (ALFF) analysis was used to compare whole-brain spontaneous neural activity between the two groups. Clinical assessments were conducted using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the short-form Intolerance of Uncertainty Scale (IUS). Pearson correlation analysis was used to examine correlations among scale scores in patients with OCD. Subsequently, with IU as the independent variable, obsessive-compulsive symptoms as the dependent variable, and ALFF values extracted from brain regions showing group differences as the mediating variable, PROCESS 4.0 for SPSS 24.0 (Model 4) was used to test the mediating role of ALFF in the pathway between IU and obsessive-compulsive symptoms. The Bootstrap method was used to test the mediation effect. Results A total of 87 participants completed the study and were included in the statistical analysis. Compared with the control group, the OCD group showed decreased ALFF values in the right cerebellar Crus II (t=-5.254, FWE-corrected P<0.01). Correlation analyses revealed that ALFF values in the right cerebellar Crus II were negatively correlated with Y-BOCS total scores (r=-0.851), compulsive behavior subscale scores (r=-0.647), IUS total scores (r=-0.617), and prospective IU subscale scores (r=-0.717) in the OCD group (all P<0.01). Prospective IU subscale scores were positively correlated with Y-BOCS total scores (r=0.811) and compulsive behavior subscale scores (r=0.535) (both P<0.01). Mediation analysis showed that ALFF values in the right cerebellar Crus II region partially mediated the effect of prospective intolerance of uncertainty scores on obsessive-compulsive behavior subscale scores, with a mediation effect of 0.064 (95% CI: 0.004–0.136), accounting for 24.57% of the total effect. Conclusion Patients with OCD showed reduced spontaneous neural activity in the right cerebellar Crus II region, which was significantly associated with intolerance of uncertainty and obsessive-compulsive symptoms. This region partially mediated the relationship between prospective uncertainty and compulsive behaviors, suggesting its potential involvement in the neural mechanisms underlying OCD.