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

New York University Child Study Center, New York University School of Medicine, New York, NY 10016, USA.
Biological psychiatry (Impact Factor: 10.26). 04/2008; 63(6):563-8. DOI: 10.1016/j.biopsych.2007.06.011
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Available from: Daniel S Pine, Sep 25, 2015
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    • "Additionally, personality traits such as neuroticism are highly comorbid with anxiety disorders (Clark et al., 1994; Hettema et al., 2004, 2006). All of these phenotypes have been the object of extensive research and have been characterized by constructs such as defensive reactivity (Lueken et al., 2013), intolerance of uncertainty (Krain et al., 2008; Simmons et al., 2008), anticipatory apprehension (Nitschke et al., 2009), emotional reactivity (Goldin et al., 2009), emotion regulation (Campbell-Sills et al., 2010), and interoceptive sensitivity (Domschke et al., 2010). "
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    • "ry group was found , with HW having longer reaction times to all picture conditions compared to LW . A possible explanation is that HW had increased cognitive evaluative processing when confronted with the stimulus material , resulting in longer reaction times . While earlier studies of uncertainty found no group differ - ences for reaction time ( Krain et al . , 2008 ; Yassa et al . , 2012 ) these data suggest that ambiguity may be an important part of uncer - tainty in a broader sense which has been largely neglected so far ."
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    • "Since we needed " novice " participants who were less likely to have prior knowledge of electricity, we recruited humanities and arts college students who had never taken optional science courses during their studies. Since individuals with anxiety disorders may have different brain activations under uncertainty in the frontal and limbic regions (Krain et al., 2008), volunteers who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders: Fourth Edition, Text Revised (DSM-IV-TR) regarding anxiety disorders were identified by the ADIS IV-R test (Newman et al., 2003) and excluded from the study (three women and six men out of a total of 32 volunteers were excluded for this reason). The remaining selected participants reported no abnormal neurological history (depression, schizophrenia, anxiety disorder, etc.). "
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