Altered resting-state amygdala-cerebellar functional connectivity is associated with intolerance of uncertainty in patients with obsessive-compulsive disorder: A longitudinal study.

J Anxiety Disord

State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

Published: August 2025


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Article Abstract

Objectives: Intolerance of uncertainty (IU) plays an important role in the pathology of obsessive-compulsive disorder (OCD). The amygdala and anterior insula (AI) appear to be important neural correlates of IU. However, the relationship between altered resting-state functional connectivity (rsFC) and IU in OCD patients has not been reported.

Methods: This study recruited 39 patients with OCD and 45 healthy controls (HC). IU was measured using the Intolerance of Uncertainty Scale (IUS). The seed-to-voxel method was used to construct rsFC maps. Between-group differences in rsFC and their correlations with IU were analyzed. Following an eight-week psychological intervention, OCD patients underwent a second assessment. The association between rsFC changes and IU changes was investigated.

Results: OCD patients exhibited significantly higher IUS scores. Significant alterations in rsFC were observed between the left amygdala and the left cerebellum posterior lobe (CPL), as well as between the left AI and the left cuneus in OCD patients. In the OCD group, only the left amygdala - left CPL rsFC significantly correlated with IUS scores. No significant correlations were found between rsFC and IUS scores in the HC group. Longitudinal analysis revealed that changes in the left amygdala - left CPL rsFC were significantly associated with changes in IUS scores.

Conclusions: This study establishes amygdala-cerebellar rsFC as a specific neural signature of IU in patients with OCD, patterns absent in healthy controls. Moreover, the amygdala-cerebellar rsFC displayed longitudinal coupling with IU changes. These findings provide novel insights into the neural mechanisms of OCD pathology.

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http://dx.doi.org/10.1016/j.janxdis.2025.103048DOI Listing

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