The Salience Network’s Role in the Association Between Intolerance of Uncertainty and Anxiety in Adolescents

Anxiety disorders are highly prevalent in children and adolescents and are they cause of with considerable impairment at home, in school, and with friends. Intolerance of uncertainty (IU), or the inability to tolerate distress resulting from ambiguity, is one factor known to contribute to the development and maintenance of anxiety. The salience network (SN) is one brain pathway thought to underlie IU and anxiety, as dysfunction in this network has been observed in those with high IU and those with anxiety disorders. The current study utilized data collected as part of an NIMH-funded neuroimaging study of adolescents (ages 12-14, n=78) presenting with mild to severe anxiety. During this study, adolescents completed self-report measures of IU (Intolerance of Uncertainty Scale – Child Version), and anxiety (Screen for Anxiety Related Disorders), a clinical interview (Anxiety Disorders Interview Schedule), and a resting state fMRI scan. Fifty-three participants contributed usable clinical and scan data. Scan data were analyzed using CONN-fMRI Functional Connectivity Toolbox v18b. Statistical analyses were completed in SPSS; moderation analyses were completed using PROCESS for SPSS software. Regression analysis was used to relate IU to anxiety symptoms. Brain analyses associating IU with SN iFC and anxiety with SN iFC were completed. SN iFC was extracted and used as a moderator in regression analyses of IU predicting anxiety. Finally, several secondary analyses were completed, including SN whole brain analysis, and moderation analyses using the SN as a moderator on the associations between the two subfactors of IU, inhibitory IU and prospective IU, and children’s anxiety symptoms. Results supported that hypothesis that IU was related to children’s anxiety symptoms; however, no other hypotheses were supported. SN connectivity was not related to children’s IU, anxiety, or on the association between. These null results may have occurred for several reasons. First, an IU-related construct may have been a better predictor of anxiety than IU in this sample. Second, brain regions outside of the SN may contribute more to child IU and anxiety than those in the SN. Third, the study may have been underpowered to detect a moderation effect using brain data in anxious youth