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.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Six-year predictors of problems in a national sample of children and youth: I.J Am Acad Child Adolesc Psychiatry. 1995; 34: 336-347
- Prevalence and development of psychiatric disorders in childhood and adolescence.Arch Gen Psychiatry. 2003; 60: 837-844
- Anxiety.The Oxford English Dictionary, 2nd ed. 1989. Oxford University Press, 2007 (OED Online. 26 Feb)
- The role of intolerance of uncertainty in etiology and maintenance.in: Heimberg R.G. Turk C.L. Mennin D.S. Generalized Anxiety Disorder: Advances in Research and Practice. Guilford Press, New York2004: 143-163
- Understanding adolescent worry: The application of a cognitive model.J Abnorm Child Psychology. 2003; 31: 55-64
- Group cognitive-behavioral therapy for generalized anxiety disorder: Treatment outcome and long-term follow-up.J Consult Clin Psychol. 2003; 71: 821-825
- Efficacy of a cognitive-behavioral treatment for generalized anxiety disorder: Evaluation in a controlled clinical trial.J Consult Clin Psychol. 2000; 68: 957-964
- Cognitive-behavioral treatment of generalized anxiety disorder among adolescents: A case series.J Am Acad Child Adolesc Psychiatry. 2003; 42: 327-330
- Behavioral expressions of intolerance of uncertainty in worry.Behav Modif. 1997; 21: 355-371
- Elevated evidence requirements and worry.Personality and Individual Differences. 1991; 12: 21-27
- Neural systems responding to degrees of uncertainty in human decision-making.Science. 2005; 310: 1680-1683
- Inverse amygdala and medial prefrontal cortex responses to surprised faces.Neuroreport. 2003; 14: 2317-2322
- A functional MRI study of human amygdala responses to facial expressions of fear versus anger.Emotion. 2001; 1: 70-83
- Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.Arch Gen Psychiatry. 2006; 64: 97-106
- Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder.Am J Psychiatry. 2006; 163: 1091-1097
- Amygdala response to fearful faces in anxious and depressed children.Arch Gen Psychiatry. 2001; 58: 1057-1063
- Social anxiety predicts amygdala activation in adolescents viewing fearful faces.Neuroreport. 2005; 16: 1671-1675
- Anterior cingulate activation in high trait anxious subjects is related to altered error processing during decision making.Biol Psychiatry. 2004; 55: 1179-1187
- An fMRI examination of developmental differences in the neural correlates of uncertainty and decision-making.J Child Psychol Psychiatry. 2006; 47: 1023-1030
- The Anxiety Disorders Interview Schedule for Children for DSM-IV, Child and Parent Versions.Psychological Corporation, San Antonio, Texas1996
- Comorbidity in childhood anxiety disorders and treatment outcome.J Am Acad Child Adolesc Psychiatry. 2001; 40: 787-794
- Information-processing factors in childhood anxiety: A review and developmental perspective.in: Vasey M.W. Dadds M.R. The Developmental Psychopathology of Anxiety. Oxford University Press, London2001: 253-277
- Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.Arch Gen Psychiatry. 2007; 64: 97-106
- Wechsler Abbreviated Scale of Intelligence (WASI).Psychological Corporation, San Antonio, Texas1999
- Manual for the Child Behavior Checklist 4-18 and 1991 Profile.University of Vermont, Burlington1991
- Why do people worry?.Personality & Individual Differences. 1994; 17: 791-802
- Multidimensional Anxiety Scale for Children.Multi-Health Systems, North Tonawanda, New York1998
- Assessment of worry in children and adolescents: An adaptation of the Penn State Worry Questionnaire.Behav Res Ther. 1997; 35: 569-581
- Improved optimization for the robust and accurate linear registration and motion correction of brain images.Neuroimage. 2002; 17: 825-841
- A global optimisation method for robust affine registration of brain images.Mel Image Anal. 2001; 5: 143-156
- Temporal autocorrelation in univariate linear modeling of FMRI data.Neuroimage. 2001; 14: 1370-1386
- General multilevel linear modeling for group analysis in FMRI.Neuroimage. 2003; 20: 1052-1063
- A three-dimensional statistical analysis for CBF activation studies in human brain.J Cereb Blood Flow Metab. 1992; 12: 900-918
- Association between amygdala hyperactivity to harsh faces and severity of social anxiety in generalized social phobia.Biol Psychiatry. 2006; 59: 424-429
- Paying attention to emotion: An fMRI investigation of cognitive and emotional Stroop tasks.Cogn Affect Behav Neurosci. 2003; 3: 81-96
- Differential occurrence of comorbidity within childhood anxiety disorders.J Clin Child Adolesc Psychol. 2003; 32: 290-295
- Generalized anxiety disorder: A preliminary test of a conceptual model.Behav Res Ther. 1998; 36: 215-226
- Serotonin transporter genotype (5-HTTLPR): Effects of neutral and undefined conditions on amygdala activation.Biol Psychiatry. 2007; 61: 1011-1014
Article info
Publication history
Published online: August 28, 2007
Accepted:
June 12,
2007
Received in revised form:
June 11,
2007
Received:
February 26,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
