Title

CHARACTERIZATION OF CHILDREN AT-RISK FOR DEVELOPING ANXIETY DISORDERS: FINDINGS FROM CLINICAL ASSESSMENTS, BEHAVIOURAL DATA AND FUNCTIONAL MAGNETIC RESONANCE IMAGING

Date of Award

Spring 2012

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences (Neuroscience and Behavioral Science)

Supervisor

Michael Van Ameringen

Co-Supervisor

Geoffrey Hall

Language

English

Committee Member

Henry Szechtman

Abstract

The aim of this research study was to examine the clinical, behavioural and neurobiological characteristics of children who are considered to be at increased risk for developing anxiety disorders. The study population included high-risk children who have at least one parent with social phobia and normal-risk control subjects. The first objective of the study was to examine the prevalence of anxiety disorders in high-risk children. We determined the proportion of high-risk children who met criteria for a psychiatric disorder using structured clinical interviews and assessed symptom severity using measures of anxiety and depression. We found the prevalence of anxiety disorders to be elevated in high-risk children with 77% meeting criteria for a lifetime psychiatric disorder. High-risk subjects also had significantly higher levels of anxiety symptoms relative to normal-risk subjects. The second objective of the study was to examine threat-related attention processing in high-risk and normal-risk children using the dot-probe attention orienting task. We compared probe detection reaction times of high-risk children and normal-risk control children when they were exposed to emotional facial stimuli. We did not find any significant within-group or between-group differences in reaction times in our high-risk and normal-risk subjects. However, we did observe a trend towards longer reaction times in high-risk subjects for all trial types relative to normal-risk subjects, which could indicate general processing deficits in the high-risk group. The third objective of this study was to examine the activity of emotion processing brain regions using functional magnetic resonance imaging (fMRI) in children who are at increased risk for developing anxiety disorders. We compared the blood oxygenation level dependant (BOLD) response while high-risk and normal-risk subjects were engaged in the dot probe attention orienting task. Using fMRI, the BOLD response was measured while subjects were exposed to masked emotional (angry, happy or neutral) facial stimuli. We found increased activation of several frontal, temporal and limbic regions in high-risk subjects relative to normal-risk subjects during the presentation of emotional facial stimuli. These regions included the prefrontal cortex, anterior cingulate, hippocampus, insula, basal ganglia and temporal regions. To our knowledge this is the first study to characterize a sample of children at-risk for anxiety disorders using clinical, behavioural and neuroimaging data. The findings from this study demonstrate that high-risk children experience heightened anxiety symptoms and that they also present with functional abnormalities of brain regions involved in emotion processing. These results highlight the need for early identification and intervention for children at-risk for anxiety disorders. Future studies should aim for longitudinal study designs combined with neuroimaging techniques to examine changes in anxiety symptoms over time and to study the effects of treatment on the function of limbic and prefrontal structures in children at-risk for anxiety disorders.

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