Elsevier

Biological Psychiatry

Volume 63, Issue 6, 15 March 2008, Pages 563-568
Biological Psychiatry

Original Article
A Functional Magnetic Resonance Imaging Investigation of Uncertainty in Adolescents with Anxiety Disorders

https://doi.org/10.1016/j.biopsych.2007.06.011Get rights and content

Background

Pediatric anxiety disorders, although highly prevalent, are understudied with little known about their pathophysiology. Intolerance of uncertainty (IU) is a trait associated with worry, a key characteristic of these disorders. Neural responses to uncertainty in healthy subjects involve the same frontal–limbic circuits that are hyper-responsive in pediatric anxiety. As such, the present study examines the relationship between IU and neural responses to uncertainty in anxious adolescents.

Methods

Sixteen adolescents (ages 13–17) diagnosed with generalized anxiety disorder and/or social phobia (ANX) and 13 non-anxious control subjects completed a decision-making task while functional magnetic resonance imaging scans were acquired.

Results

The ANX group endorsed greater task-related anxiety and less certainty than control subjects on a post-task questionnaire. Compared with control subjects, the ANX group did not demonstrate hyper-responsivity of brain regions as hypothesized. Across groups, IU was positively correlated with activity in several frontal and limbic regions. Further analyses identified subgroups within the ANX group: those with high IU activated frontal/limbic regions, whereas those with low IU and less anxiety during the task deactivated the same regions in response to uncertainty.

Conclusions

Results substantiate the hypothesized link between IU and neural responses to uncertainty in some adolescents with anxiety disorders. Our findings, if replicated, suggest that trait measures, such as IU, can significantly improve our understanding of the neurobiological basis of pediatric anxiety disorders.

Section snippets

Participants

Eighteen adolescents with an anxiety disorder diagnosis (10 boys), ages 13–17 years (mean = 15.4; SD = 1.3), and 17 healthy adolescents (9 boys), ages 13–17 years (mean = 15.4; SD = 1.3) were scanned. Of these participants, 6 were excluded because of scanner-related imaging artifacts (2 control subjects, 1 anxious) or incomplete behavioral data (2 control subjects, 1 anxious). As a result, complete data from 16 adolescents with an anxiety disorder diagnosis (mean age = 15.2 years; SD = 1.3; 9

Behavioral Results

The ANX and control groups did not differ significantly on age, IQ, SES, and gender. Furthermore, these variables were not significantly related to behavioral variables of interest including IUS scores, task-based measures (response time, accuracy, and variability), and scores on the post-scan questionnaire.

Discussion

This is the first study to link IU in participants with anxiety disorders to the neural substrates believed to underlie these disorders. High levels of IU characteristic of clinical anxiety were associated with increased activation in frontal and limbic regions in response to uncertainty, consistent with study hypotheses. An unexpected finding was that adolescents with anxiety disorders demonstrated different patterns of neural responsiveness depending upon IU: those who endorsed low IU showed

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      This pattern of results could be interpreted as evidence that questionnaire measures of IU may capture subjective, affective reactions to uncertainty when pre-adolescent children self-report. This is consistent with the findings of Krain and colleagues (Krain et al., 2006; Krain et al., 2008) who also found that self-reported IU was associated with subjective worry and certainty but not behavioural measures such as decision making time. Parents, on the other hand, may be more likely to respond to items on the questionnaire measure of IU on the basis of observable behaviour and we may therefore expect to see more associations with behaviour when we use parent-report of IU.

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