Monk CS, Telzer EH, Mogg K, Bradley BP, Mai XQ, Louro HMC et al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiat 65: 568-576

Department of Psychology, University of Michigan, 530 Church St, Ann Arbor, MI 48109-1043, USA.
Archives of general psychiatry (Impact Factor: 14.48). 06/2008; 65(5):568-76. DOI: 10.1001/archpsyc.65.5.568
Source: PubMed


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.
To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD.
Case-control study.
Government clinical research institute.
Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis.
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.
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.
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.

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    • "In adulthood, increased amygdala activity is associated with major depressive disorder (Drevets, 2001; Sheline et al., 2001), and generalized social phobia (Evans et al., 2008; Phan et al., 2006). In adolescence, the amygdala was found to yield stronger responses to fearful faces than adults (Thomas et al., 2001), and greater amygdala reactivity may account for adolescent vulnerability to mood disorders (Guyer, Lau, et al., 2008; Monk et al., 2008; Roberson-Nay et al., 2006). In consideration of the amygdala's role in the endocannabinoid system and affective processing, adolescent vulnerability to mood disorders and propensity for cannabis use, it is important to assess functional differences in this region in cannabis-using teenagers. "
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    • "Symptom severity was negatively correlated with vlPFC activation, suggesting that vlPFC recruitment may be a compensatory mechanism to regulate anxiety (Guyer et al; 2013; Shechner et al., 2012). With pre-conscious face presentation (17ms), adolescents with GAD showed greater amygdala response to angry faces, as well as a reduced negative amygdala-vlPFC coupling (Monk et al., 2008). "
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    • "As in PTSD, GAD patients showed increased activity in the limbic circuitry, especially in the amygdala and insula [93] [94]. Also similar to PTSD patients, patients with GAD showed increased right amygdala activity when viewing angry faces; this activity was negatively correlated with ventrolateral PFC activity [95]. Finally, changes in prefrontal-limbic activity may modulate symptoms of panic disorder. "
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