New Research
Intrinsic Functional Connectivity of Amygdala-Based Networks in Adolescent Generalized Anxiety Disorder

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Objective

Generalized anxiety disorder (GAD) typically begins during adolescence and can persist into adulthood. The pathophysiological mechanisms underlying this disorder remain unclear. Recent evidence from resting state functional magnetic resonance imaging (R-fMRI) studies in adults suggests disruptions in amygdala-based circuitry; the present study examines this issue in adolescents with GAD.

Method

Resting state fMRI scans were obtained from 15 adolescents with GAD and 20 adolescents without anxiety who were group matched on age, sex, scanner, and intelligence. Functional connectivity of the centromedial, basolateral, and superficial amygdala subdivisions was compared between groups. We also assessed the relationship between amygdala network dysfunction and anxiety severity.

Results

Adolescents with GAD exhibited disruptions in amygdala-based intrinsic functional connectivity networks that included regions in medial prefrontal cortex, insula, and cerebellum. Positive correlations between anxiety severity scores and amygdala functional connectivity with insula and superior temporal gyrus were also observed within the GAD group. There was some evidence of greater overlap (less differentiation of connectivity patterns) of the right basolateral and centromedial amygdala networks in the adolescents with, relative to those without, GAD.

Conclusions

These findings suggest that adolescents with GAD manifest alterations in amygdala circuits involved in emotion processing, similar to findings in adults. In addition, disruptions were observed in amygdala-based networks involved in fear processing and the coding of interoceptive states.

Section snippets

Method

An advantage of R-fMRI is that although scanner- and site-related variation is detectable, robust effects associated with phenotypic variables such as diagnosis are discernible when data from multiple sites are combined.21, 22, 23, 24 We exploit this robustness to combine datasets from two sites to attain sufficiently large samples of medication-free pediatric participants.

Participants (12–17 years of age) were recruited across two sites, the New York University (NYU) Child Study Center, and

Results

As shown in Table 1, no group differences were observed for sex, age, IQ, race/ethnicity, or movement (maximum displacement) during the resting state scan, or the percentage of participants from each site. Scores on the SCARED-PC were significantly higher for the GAD group than the healthy comparison group (t32 = 8.2, p< .001).

Discussion

Study findings have revealed alterations in iFC of individual amygdala subdivisions with prefrontal regions, consistent with emotion regulation models of GAD.33 Additional iFC group differences were observed in the striatum, insula, superior temporal gyrus, brainstem, and cerebellum, suggesting more widespread disruption of amygdala networks in adolescent GAD than observed previously in task-based studies. We discuss these findings in terms of specific cognitive processes likely involved in

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    The content is solely the responsibility of the authors and does not necessarily represent the official views of NIMH or the National Institutes of Health.

    The project described was supported by NIMH Career Development Award K23 MH074821 (A.K.R.).

    Supplemental material cited in this article is available online.

    The authors thank the participants and their families as well as Rachel Chizkov, B.A., of the New York University Child Study Center for her assistance in assembling the necessary datasets.

    Disclosure: Drs. Roy, Fudge, Kelly, Benson, Castellanos, Milham, Pine, and Ernst, and Mr. Perry, Ms. Daniele, and Ms. Carlisi report no biomedical financial interests or potential conflicts of interest.

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