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Amygdala and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents With Generalized Anxiety Disorder
Christopher S. Monk, PhD;
Eva H. Telzer, MA;
Karin Mogg, PhD;
Brendan P. Bradley, PhD;
Xiaoqin Mai, PhD;
Hugo M. C. Louro, MSE;
Gang Chen, PhD;
Erin B. McClure-Tone, PhD;
Monique Ernst, MD, PhD;
Daniel S. Pine, MD
Arch Gen Psychiatry. 2008;65(5):568-576.
Context Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly presented threats in GAD or in pediatric anxiety.
Objective To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD.
Design Case-control study.
Setting Government clinical research institute.
Participants Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis.
Main Outcome Measures We used functional magnetic resonance imaging to measure blood oxygenation level–dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces.
Results When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects.
Conclusions Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.
Author Affiliations: Departments of Psychology (Dr Monk and Mr Louro) and Psychiatry (Dr Monk) and Center for Human Growth and Development (Drs Monk and Mai), University of Michigan, Ann Arbor; Department of Psychology, University of California, Los Angeles (Ms Telzer); School of Psychology, University of Southampton, Southampton, England (Drs Mogg and Bradley); Scientific and Statistical Computing Core (Dr Chen) and Mood and Anxiety Disorders Program (Drs Ernst and Pine), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; and Department of Psychology, Georgia State University, Atlanta (Dr McClure-Tone).
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