A hierarchical uncertainty framework of anxiety: Preregistered meta-analytic structural model of intolerance of uncertainty and worry across anxiety disorders.
Level 3 - non-randomized controlled study
Meta-analysis and structural equation modeling of observational and correlational studies
PubMed 42419154 · doi:10.1016/j.cpr.2026.102773
What was done
A pre-registered meta-analysis and meta-analytic structural equation model evaluated relationships among intolerance of uncertainty (IU), worry, and anxiety outcomes across clinical phenotypes and methodological moderators. The analysis synthesized 738 effect sizes from 115 studies or dissertations encompassing 138 independent samples (N = 28,693).
What was found
IU was robustly associated with worry (r = .59) and showed a hierarchical association with specific anxiety disorders: generalized anxiety disorder (GAD; r = .54), non-specific anxiety (r = .48), PTSD (r = .46), social anxiety disorder (r = .45), OCD (r = .41), and panic disorder (r = .27). Worry was strongly associated with GAD (r = .67) and partially mediated the IU-anxiety relationship, with indirect effects ranging from r = .32 (GAD) to r = .13 (OCD). Overlapping self-report measurement inflated effect sizes for IU-GAD, IU-non-specific anxiety, and worry-non-specific anxiety (p < .05), but weakened IU-OCD associations. Concurrent depressive symptoms also attenuated IU-anxiety links.
Why it matters
This framework demonstrates that the transdiagnostic role of intolerance of uncertainty varies along a disorder-specific hierarchy, positioning IU as a distal vulnerability and worry as a proximal mediator.
Limits
The synthesized literature relies primarily on cross-sectional and correlational designs, preventing causal confirmation of the temporal sequence. Measurement overlap in self-report instruments inflated multiple effect sizes, and co-occurring depressive symptoms confounded phenotype-specific associations.