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Dynamic changes in amygdala activation and functional connectivity in children and adolescents with anxiety disorders

Published online by Cambridge University Press:  25 November 2014

Johnna R. Swartz*
Affiliation:
University of Michigan, Ann Arbor
K. Luan Phan
Affiliation:
University of Michigan, Ann Arbor
Mike Angstadt
Affiliation:
University of Michigan, Ann Arbor
Kate D. Fitzgerald
Affiliation:
University of Michigan, Ann Arbor
Christopher S. Monk
Affiliation:
University of Michigan, Ann Arbor
*
Address correspondence and reprint requests to: Johnna R. Swartz, Center for Developmental Science, University of North Carolina at Chapel Hill, 100 East Franklin Street, Suite 200, CB 8115, Chapel Hill, NC 27599; E-mail: jrswartz@live.unc.edu.

Abstract

Anxiety disorders are associated with abnormalities in amygdala function and prefrontal cortex–amygdala connectivity. The majority of functional magnetic resonance imaging studies have examined mean group differences in amygdala activation or connectivity in children and adolescents with anxiety disorders relative to controls, but emerging evidence suggests that abnormalities in amygdala function are dependent on the timing of the task and may vary across the course of a scanning session. The goal of the present study was to extend our knowledge of the dynamics of amygdala dysfunction by examining whether changes in amygdala activation and connectivity over scanning differ in pediatric anxiety disorder patients relative to typically developing controls during an emotion processing task. Examining changes in activation over time allows for a comparison of how brain function differs during initial exposure to novel stimuli versus more prolonged exposure. Participants included 34 anxiety disorder patients and 19 controls 7 to 19 years old. Participants performed an emotional face-matching task during functional magnetic resonance imaging scanning, and the task was divided into thirds in order to examine change in activation over time. Results demonstrated that patients exhibited an abnormal pattern of amygdala activation characterized by an initially heightened amygdala response relative to controls at the beginning of scanning, followed by significant decreases in activation over time. In addition, controls evidenced greater context-modulated prefrontal cortex–amygdala connectivity during the beginning of scanning relative to patients. These results indicate that differences in emotion processing between the groups vary from initial exposure to novel stimuli relative to more prolonged exposure. Implications are discussed regarding how this pattern of neural activation may relate to altered early-occurring or anticipatory emotion-regulation strategies and maladaptive later-occurring strategies in children and adolescents with anxiety disorders.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2014 

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References

Adolphs, R. (2010). What does the amygdala contribute to social cognition? Annals of the New York Academy of Sciences, 1191, 4261.Google Scholar
Ashburner, J. (2007). A fast diffeomorphic image registration algorithm. NeuroImage, 38, 95113.CrossRefGoogle ScholarPubMed
Battaglia, M., Zanoni, A., Taddei, M., Giorda, R., Bertoletti, E., Lampis, V., et al. (2012). Cerebral responses to emotional expressions and the development of social anxiety disorder: A preliminary longitudinal study. Depression and Anxiety, 29, 5461.CrossRefGoogle ScholarPubMed
Beesdo, K., Lau, J. Y. F., Guyer, A. E., McClure-Tone, E. B., Monk, C. S., Nelson, E. E., et al. (2009). Common and distinct amygdala-function perturbations in depressed vs. anxious adolescents. Archives of General Psychiatry, 66, 275285.Google Scholar
Blair, K. S., Geraci, M., Korelitz, K., Otero, M., Towbin, K., Ernst, M., et al. (2011). The pathology of social phobia is independent of developmental changes in face processing. American Journal of Psychiatry, 168, 12021209.CrossRefGoogle ScholarPubMed
Bogdan, R., Williamson, D. E., & Hariri, A. R. (2012). Minerlocorticoid receptor iso/val (rs5522) genotype moderates the association between previous childhood emotional neglect and amygdala reactivity. American Journal of Psychiatry, 169, 515522.Google Scholar
deCharms, R. C., Maeda, F., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., et al. (2005). Control over brain activation and pain learned by using real-time functional MRI. Proceedings of the National Academy of Sciences, 102, 1862618631.CrossRefGoogle ScholarPubMed
Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: A meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. American Journal of Psychiatry, 164, 14761488.CrossRefGoogle ScholarPubMed
First, M. B., Gibbon, M., & Williams, J. B. W. (1997). Structured Clinical Interview for DSM-IV Axis I disorders (SCID). New York: New York State Psychiatric Institute, Biometrics Research.Google Scholar
Forbes, E. E., Phillips, M. L., Silk, J. S., Ryan, N. D., & Dahl, R. E. (2011). Neural systems of threat processing in adolescents: Role of pubertal maturation and relation to measures of negative affect. Developmental Neuropsychology, 36, 429452.Google Scholar
Friston, K. J., Buechel, C., Fink, G. R., Morris, J., Rolls, E., & Dolan, R. J. (1997). Psychophysiological and modulatory interactions in neuroimaging. NeuroImage, 6, 218229.CrossRefGoogle ScholarPubMed
Gee, D. G., Humphreys, K. L., Flannery, J., Goff, B., Telzer, E. H., Shapiro, M., et al. (2013). A developmental shift from positive to negative connectivity in human amygdala–prefrontal circuitry. Journal of Neuroscience, 33, 45844593.Google Scholar
Goldin, P. R., Manber-Ball, T., Werner, K., Heimberg, R., & Gross, J. J. (2009). Neural mechanisms of cognitive reappraisal of negative self-beliefs in social anxiety disorder. Biological Psychiatry, 66, 10911099.Google Scholar
Goldin, P. R., McRae, K., Ramel, W., & Gross, J. J. (2008). The neural bases of emotion regulation: Reappraisal and suppression of negative emotion. Biological Psychiatry, 63, 577586.Google Scholar
Gur, R. C., Sara, R., Hagendoorn, M., Marom, O., Hughett, P., Macy, L., et al. (2002). A method for obtaining 3-dimensional facial expressions and its standardization for use in neurocognitive studies. Journal of Neuroscience Methods, 115, 137143.CrossRefGoogle ScholarPubMed
Guyer, A. E., Lau, J. Y. F., McClure-Tone, E. B., Parrish, J. M., Shiffrin, N. D., Reynolds, R. C., et al. (2008). Amygdala and ventrolateral prefrontal cortex function during anticipated peer evaluation in pediatric social anxiety. Archives of General Psychiatry, 65, 13031312.Google Scholar
Hariri, A. R., Drabant, E. M., & Weinberger, D. R. (2006). Imaging genetics: Perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective procesing. Biologial Psychiatry, 59, 888897.CrossRefGoogle Scholar
Hariri, A. R., Tessitore, A., Mattay, V. S., Fera, F., & Weinberger, D. R. (2002). The amygdala response to emotional sitmuli: A comparison of faces and scenes. NeuroImage, 17, 317323.Google Scholar
Hattingh, C. J., Ipser, J., Tromp, S. A., Syal, S., Lochner, C., Brooks, S. J., et al. (2013). Functional magnetic resonance imaging during emotion recognition in social anxiety disorder: An activation likelihood meta-analysis. Frontiers in Human Neuroscience, 6, 17.Google Scholar
Hyde, L. W., Bogdan, R., & Hariri, A. R. (2011). Understanding risk for psychopathology through imaging gene–environment interactions. Trends in Cognitive Science, 15, 417427.Google Scholar
Johnston, S. J., Boehm, S. G., Healy, D., Goebel, R., & Linden, D. E. J. (2010). Neurofeedback: A promising tool for the self-regulation of emotion networks. NeuroImage, 49, 10661072.CrossRefGoogle ScholarPubMed
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., et al. (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 980988.Google Scholar
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62, 593602.Google Scholar
King, C. A., Klaus, N., Kramer, A., Venkataraman, S., Quinlan, P., & Gillespie, B. (2009). The Youth-Nominated Support Team—Version II for suicidal adolescents: A randomized controlled intervention trial. Journal of Consulting and Clinical Psychology, 77, 880893.Google Scholar
Larson, C. L., Schaefer, H. S., Siegle, G. J., Jackson, C. A. B., Anderle, M. J., & Davidson, R. J. (2006). Fear is fast in phobic individuals: Amygdala activation in response to fear-relevant stimuli. Biological Psychiatry, 60, 410417.Google Scholar
Linden, D. E. J., Habes, I., Johnston, S. J., Linden, S., Tatineni, R., Subramanian, L., et al. (2012). Real-time self-regulation of emotion networks in patients with depression. PLOS One, 7, e38115.Google Scholar
Maldjian, J. A., Laurienti, P. J., Kraft, R. A., & Burdette, J. H. (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage, 19, 12331239.Google Scholar
March, J. S., Parker, J. D., Sullivan, K., Stallings, P., & Conners, C. K. (1997). The Multidimensional Anxiety Scale for Children (MASC): Factor structure, reliability, and validity. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 554565.CrossRefGoogle ScholarPubMed
Masia-Warner, C., Storch, E. A., Pincus, D. B., Klein, R. G., Heimberg, R. G., & Liebowitz, M. R. (2003). The Liebowitz social anxiety scale for children and adolescents: An initial psychometric investigation. Journal of the American Academy of Child & Adolescent Psychiatry, 42, 10761084.Google Scholar
McClure, E. B., Monk, C. S., Nelson, E. E., Parrish, J. M., Adler, A., Blair, J. R., et al. (2007). Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Archives of General Psychiatry, 64, 97106.Google Scholar
Monk, C. S., Nelson, E. E., McClure, E. B., Mogg, K., Bradley, B. P., Leibenluft, E., et al. (2006). Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. American Journal of Psychiatry, 163, 10911097.Google Scholar
Monk, C. S., Telzer, E. H., Mogg, K., Bradley, B. P., Mai, X., Louro, H. M. C., et al. (2008). Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Archives of General Psychiatry, 65, 568576.Google Scholar
Moore, W. E., Pfeifer, J. H., Masten, C. L., Mazziotta, J. C., Iacoboni, M., & Dapretto, M. (2012). Facing puberty: Associations between pubertal development and neural responses to affective facial displays. Social Cognitive and Affective Neuroscience, 7, 3543.CrossRefGoogle ScholarPubMed
Munafo, M. R., Brown, S. M., & Hariri, A. R. (2008). Serotonin transporter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biological Psychiatry, 63, 852857.CrossRefGoogle ScholarPubMed
Paulus, M. P., & Stein, M. B. (2007). Role of functional magnetic resonance imaging in drug discovery. Neuropsychology Review, 17, 179188.Google Scholar
Petersen, A., Crockett, L., Richards, M., & Boxer, A. (1988). A self-report measure of pubertal status: Reliability, validity, and initial norms. Journal of Youth and Adolescence, 17, 117133.Google Scholar
Phillips, M. L., Ladouceur, C. D., & Drevets, W. C. (2008). A neural model of voluntary and automatic emotion regulation: Implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Molecular Psychiatry, 13, 829, 833–857.Google Scholar
Pine, D. S. (2007). Research review: A neuroscience framework for pediatric anxiety disorders. Journal of Child Psychology and Psychiatry, 48, 631648.Google Scholar
Prater, K. E., Hosanagar, A., Klumpp, H., Angstadt, M., & Phan, K. L. (2013). Aberrant amygdala–frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder. Depression and Anxiety, 30, 234241.Google Scholar
Ray, R. D., & Zald, D. H. (2012). Anatomical insights into the interaction of emotion and cognition in the prefrontal cortex. Neuroscience & Biobehavioral Reviews, 36, 479501.Google Scholar
Sladky, R., Hoflich, A., Atanelov, J., Kraus, C., Baldinger, P., Moser, E., et al. (2012). Increased neural habituation in the amygdala and orbitofrontal cortex in social anxiety disorder revealed by fMRI. PLOS One, 7, e50050.Google Scholar
Swartz, J. R., Carrasco, M., Wiggins, J. L., Thomason, M. E., & Monk, C. S. (2014). Age-related changes in the structure and function of prefrontal cortex–amygdala circuitry in children and adolescents: A multi-modal imaging approach. NeuroImage, 86, 212220.Google Scholar
Swartz, J. R., & Monk, C. S. (2014a). The role of corticolimbic circuitry in the development of anxiety disorders in children and adolescents. In Anderson, S. & Pine, D. (Eds.), Current topics in behavioral neuroscience: The neurobiology of childhood (pp. 133148). New York: Springer.Google Scholar
Swartz, J. R., & Monk, C. S. (2014b). Functional magnetic resonance imaging in developmental psychopathology: The brain as a window into the development and treatment of psychopathology. In Lewis, M. & Rudolph, K. (Eds.), Handbook of developmental psychopathology (3rd ed., pp. 265286). New York: Springer.Google Scholar
Verduin, T. L., & Kendall, P. C. (2003). Differential occurrence of comorbidity within childhood anxiety disorders. Journal of Clinical Child and Adolescent Psychology, 32, 290295.CrossRefGoogle ScholarPubMed
Viding, E., Williamson, D. E., & Hariri, A. R. (2006). Developmental imaging genetics: Challenges and promises for translational research. Development and Psychopathology, 18, 877892.Google Scholar
White, M. G., Bogdan, R., Fisher, P. M., Munoz, K. E., Williamson, D. E., & Hariri, A. R. (2012). FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity. Genes, Brain and Behavior, 11, 869878.Google Scholar
Ziv, M., Goldin, P. R., Jazaieri, H., Hahn, K. S., & Gross, J. J. (2013). Is there less to social anxiety than meets the eye? Behavioral and neural responses to three socio-emotional tasks. Biology of Mood and Anxiety Disorders, 3, 5.Google Scholar