Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder.
BACKGROUND
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.


METHODS
Case-control study.


METHODS
Government clinical research institute.


METHODS
Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis.


METHODS
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.
Monk
Christopher S
CS
Department of Psychology, University of Michigan, 530 Church St, Ann Arbor, MI 48109-1043, USA. csmonk@umich.edu
Telzer
Eva H
EH
Mogg
Karin
K
Bradley
Brendan P
BP
Mai
Xiaoqin
X
Louro
Hugo M C
HM
Chen
Gang
G
McClure-Tone
Erin B
EB
Ernst
Monique
M
Pine
Daniel S
DS
D000293:Adolescent; D000679:Amygdala / Q000503:physiopathology*; D000786:Anger; D001008:Anxiety Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology*; D001288:Attention; D002648:Child; D005149:Facial Expression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010470:Perceptual Masking / Q000502:physiology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012720:Severity of Illness Index