Abnormal Attention Modulation of Fear Circuit Function in Pediatric Generalized Anxiety Disorder

Emotional Development and Affective Neuroscience Branch, Mood and Anxiety Disorders Program, National Institute of Mental Health, NIH/DHHS, Bethesda, MD 20892, USA.
Archives of General Psychiatry (Impact Factor: 14.48). 02/2007; 64(1):97-106. DOI: 10.1001/archpsyc.64.1.97
Source: PubMed


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.
To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents.
Case-control study.
Government clinical research institute.
Fifteen adolescents with generalized anxiety disorder and 20 controls.
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.
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.
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.

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    • "Our preliminary observation that MBCT-C increased activation in the cingulate cortex is noteworthy, given that this structure subserves the contemporaneous processing of cognitive and emotional information, and integrates these two streams (Yamasaki et al. 2002). fMRI studies of this region in youth with GAD have revealed increased activation during the viewing of fearful faces (McClure et al. 2007) and ACC activation correlates with amygdala and VLPFC activation in youth with GAD. Further, in the present sample, baseline activation of this structure predicted treatment-associated changes in anxiety symptoms. "
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    • "The CON provided stable 'set-maintenance' over entire task epochs (Dosenbach et al., 2007). Furthermore, a wealth of evidence indicated a disruption during the processing of emotional stimuli in dACC, one of the main regions in the CON (Amir et al., 2005; McClure et al., 2007; Simmons et al., 2008; Hayes et al., 2009; Shin and Liberzon, 2010; Etkin et al., 2014). The abnormal connectivity of visual network (VIS) might implicate impaired emotional visual information processing in major depressive disorder (MDD) (Zeng et al., 2012; Ma et al., 2013). "
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    • "Significant volume changes in the PFC were only detected for WM but not for GM, contrary to hypotheses. Previous structural (e.g., Schienle et al., 2011; Strawn et al., 2013; Strawn et al., 2014) and functional (e.g., McClure et al., 2007; Strawn et al., 2012; Ball et al., 2013) MRI studies have reported abnormal GM volume in various parts of the PFC, although not in all studies (Liao et al., 2014; Moon et al., 2014). Additionally, structural PFC alterations are present in disorders related to GAD such as major depression (Kempton et al., 2011; Du et al., 2012; Sacher et al., 2012). "
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