Article

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: 9.47). 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.

Full-text

Available from: Daniel S Pine, May 30, 2015
0 Followers
 · 
121 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study reviews research on the construct of intolerance of uncertainty (IU). A recent factor analysis (Journal of Anxiety Disorders, 25, 2012, p. 533) has been used to extend the transdiagnostic model articulated by Mansell (2005, p. 141) to focus on the role of IU as a facet of the model that is important to address in treatment. Research suggests that individual differences in IU may compromise resilience and that individuals high in IU are susceptible to increased negative affect. The model extension provides a guide for the treatment of clients presenting with uncertainty in the context of either a single disorder or several comorbid disorders. By applying the extension, the clinician is assisted to explore two facets of IU, “Need for Predictability” and “Uncertainty Arousal.”
    Clinical Psychology Science and Practice 09/2014; 21(3). DOI:10.1111/cpsp.12077 · 2.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Social anxiety disorder (SAD) is one of the most frequent anxiety disorders. The landmark meta-analysis of functional neuroimaging studies by Etkin & Wager (2007) revealed primarily the typical fear circuit as overactive in SAD. Since then, new methodological developments such as functional connectivity and more standardized structural analyses of grey and white matter have been developed. We provide a comprehensive update and a meta-analysis of neuroimaging studies in SAD since 2007 and present a new model of the neurobiology of SAD. We confirmed the hyperactivation of the fear circuit (amygdala, insula, anterior cingulate and prefrontal cortex) in SAD. In addition, task-related functional studies revealed hyperactivation of medial parietal and occipital regions (posterior cingulate, precuneus, cuneus) in SAD and a reduced connectivity between parietal and limbic and executive network regions. Based on the result of this meta-analysis and review, we present an updated model of SAD adopting a network-based perspective. The disconnection of the medial parietal hub in SAD extends current frameworks for future research in anxiety disorders.
    Neuroscience & Biobehavioral Reviews 11/2014; 47:260-280. DOI:10.1016/j.neubiorev.2014.08.003 · 10.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Children with anxiety disorders (ADs) experience persistent fear and worries that are highly debilitating, conferring risk for lifelong psychopathology. Anticipatory anxiety is a core clinical feature of childhood ADs, often leading to avoidance of uncertain and novel situations. Extensive studies in non-human animals implicate amygdala dysfunction as a critical substrate for early life anxiety. To test specific amygdala-focused hypotheses in preadolescent children with ADs, we used fMRI to characterize amygdala activation during uncertain anticipation and in response to unexpected stimuli. Forty preadolescent (age 8-12) children, 20 un-medicated AD patients and 20 matched controls, completed an anticipation task during an fMRI scan. In the task, symbolic cues preceded fear or neutral faces, such that 'certain' cues always predicted the presentation of fear or neutral faces, whereas 'uncertain' cues were equally likely to be followed by fear or neutral faces. Both AD children and controls showed robust amygdala response to faces. In response to the uncertain cues, AD children had increased amygdala activation relative to controls. Moreover, in the AD children, faces preceded by an 'uncertain' cue elicited increased amygdala activation, as compared to the same faces following a 'certain' cue. Children with ADs experience distress both in anticipation of and during novel and surprising events. Our findings suggest that increased amygdala activation may play an important role in the generation of uncertainty-related anxiety. These findings may guide the development of neuroscientifically-informed treatments aimed at relieving the suffering and preventing the lifelong disability associated with pediatric ADs.Neuropsychopharmacology accepted article preview online, 15 December 2014. doi:10.1038/npp.2014.328.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2014; 40(6). DOI:10.1038/npp.2014.328 · 7.83 Impact Factor