Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.
BACKGROUND
Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues.


OBJECTIVE
To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents.


METHODS
Case-control study.


METHODS
Government clinical research institute.


METHODS
Fifteen adolescents with generalized anxiety disorder and 20 controls.


METHODS
Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention.


RESULTS
While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex.


CONCLUSIONS
This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.
McClure
Erin B
EB
Emotional Development and Affective Neuroscience Branch, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH/DHHS, Bethesda, MD 20892, USA. emcclure@gsu.edu
Monk
Christopher S
CS
Nelson
Eric E
EE
Parrish
Jessica M
JM
Adler
Abby
A
Blair
R James R
RJ
Fromm
Stephen
S
Charney
Dennis S
DS
Leibenluft
Ellen
E
Ernst
Monique
M
Pine
Daniel S
DS
D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology; D000679:Amygdala / Q000503:physiopathology; D001008:Anxiety Disorders / Q000175:diagnosis / Q000503:physiopathology* / Q000523:psychology; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D003463:Cues; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D005239:Fear / Q000502:physiology*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000503:physiopathology; D012938:Social Perception; D014796:Visual Perception / Q000502:physiology
D010100:Oxygen