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Anxiety is related to indices of cortical maturation in typically develo** children and adolescents

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Abstract

Anxiety is a risk factor for many adverse neuropsychiatric and socioeconomic outcomes, and has been linked to functional and structural changes in the ventromedial prefrontal cortex (VMPFC). However, the nature of these differences, as well as how they develop in children and adolescents, remains poorly understood. More effective interventions to minimize the negative consequences of anxiety require better understanding of its neurobiology in children. Recent research suggests that structural imaging studies may benefit from clearly delineating between cortical surface area and thickness when examining these associations, as these distinct cortical phenotypes are influenced by different cellular mechanisms and genetic factors. The present study examined relationships between cortical surface area and thickness of the VMPFC and a self-report measure of anxiety (SCARED-R) in 287 youths aged 7–20 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Age and gender interactions were examined for significant associations in order to test for developmental differences. Cortical surface area and thickness were also examined simultaneously to determine whether they contribute independently to the prediction of anxiety. Anxiety was negatively associated with relative cortical surface area of the VMPFC as well as with global cortical thickness, but these associations diminished with age. The two cortical phenotypes contributed additively to the prediction of anxiety. These findings suggest that higher anxiety in children may be characterized by both delayed expansion of the VMPFC and an altered trajectory of global cortical thinning. Further longitudinal studies will be needed to confirm these findings.

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Acknowledgments

This work was supported by the National Institute On Drug Abuse (grant number RC2 DA029475), the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (Grant Number R01 HD061414), and the National Institute of General Medical Sciences (Grant Number R01 GM104400) of the National Institutes of Health. The content presented herein is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. These data are freely available on the PING portal: http://**study.ucsd.edu.

Data reported herein represent a subset of the data collected in the PING study. PING is a multisite initiative consisting of six infrastructure cores and 10 data collection sites. The following is a description of key personnel in the infrastructure cores: Coordinating Core, Core PI and Co-PI of PING Terry L. Jernigan, Ph.D., and Connor McCabe, B.S., UC San Diego; Assessment Core, Core PI and Co-PI of PING Linda Chang, M.D., U Hawaii, Natacha Akshoomoff, Ph.D., UC San Diego, Erik Newman, Ph.D., UC San Diego; MRI Post-processing Core, Core PI and Co-PI of PING Anders M. Dale, Ph.D., UC San Diego; MRI Acquisition Core, Core PI and Co-PI of PING Thomas Ernst, Ph.D., U Hawaii, Core Co-PI Anders M. Dale, Ph.D., UC San Diego, Peter Van Zijl, Ph.D., KKI, Joshua Kuperman, Ph.D., UC San Diego; Genetics Core, Core PI and Co-PI of PING Sarah Murray, Ph.D., Cinnamon Bloss, Ph.D., and Nicholas J. Schork, Ph.D., Scripps Translational Science Institute; Informatics and Biostatistics, Mark Appelbaum, Ph.D., Anthony Gamst, Ph.D., Wesley Thompson, Ph.D., and Hauke Bartsch, Ph.D., UC San Diego. The following is a description of the key personnel at the data collection sites: University of California, San Diego, Site PI Terry L. Jernigan, Ph.D., Anders M. Dale, Ph.D., Natacha Akshoomoff, Ph.D.; University of Hawaii, Site PI Linda Chang, M.D., Thomas Ernst, Ph.D., Brian Keating, Ph.D.; University of California, Davis, Site PI David Amaral, Ph.D.; University of California, Los Angeles, Site PI Elizabeth Sowell, Ph.D.; Kennedy Krieger Institute, Johns Hopkins University, Site PIs Walter Kaufmann, M.D. and Stewart Mostofsky, M.D., Peter Van Zijl, Ph.D.; Sackler Institute, Weill Cornell Medical College, Site PI B.J. Casey, Ph.D., Erika J. Ruberry, B.A., Alisa Powers, B.A.; Massachusetts General Hospital, Harvard University, Site PIs Bruce Rosen, M.D., Ph.D. and Tal Kenet, Ph.D.; University of Massachusetts, Site PIs Jean Frazier, M.D. and David Kennedy, Ph.D.; Yale University, Site PI Jeffrey Gruen, M.D.

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Authors and Affiliations

  1. Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA

    Erik Newman, Connor McCabe, Yoonho Chung, Natacha Akshoomoff & Terry L. Jernigan

  2. Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA

    Erik Newman, Wesley K. Thompson, Chi-Hua Chen, Natacha Akshoomoff & Terry L. Jernigan

  3. Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA

    Wesley K. Thompson

  4. Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA

    Hauke Bartsch, Donald J. Hagler Jr., Chi-Hua Chen, Timothy T. Brown, Joshua M. Kuperman, Yoonho Chung & Anders M. Dale

  5. Department of Radiology, University of California, San Diego, La Jolla, CA, USA

    Donald J. Hagler Jr., Joshua M. Kuperman, Anders M. Dale & Terry L. Jernigan

  6. Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA

    Timothy T. Brown & Anders M. Dale

  7. Department of Psychology, University of Washington, Seattle, WA, USA

    Connor McCabe

  8. Department of Psychology, Yale University, New Haven, CT, USA

    Yoonho Chung

  9. Scripps Genomic Medicine, Scripps Translational Science Institute and Scripps Health, La Jolla, CA, USA

    Ondrej Libiger, Cinnamon S. Bloss & Nicholas Schork

  10. Sackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY, USA

    B. J. Casey

  11. Department of Medicine, University of Hawaii and Queen’s Medical Center, Honolulu, HI, USA

    Linda Chang & Thomas M. Ernst

  12. Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, USA

    Jean A. Frazier & David N. Kennedy

  13. Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA

    Jeffrey R. Gruen

  14. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

    Jeffrey R. Gruen

  15. Department of Pathology, University of California, San Diego, La Jolla, CA, USA

    Sarah S. Murray

  16. Department of Pediatrics, University of Southern California, Los Angeles, CA, USA

    Elizabeth R. Sowell

  17. Children’s Hospital, Los Angeles, CA, USA

    Elizabeth R. Sowell

  18. Department of Neurology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA

    Tal Kenet

  19. Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA

    Walter E. Kaufmann

  20. Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Stewart Mostofsky

  21. Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA, USA

    David G. Amaral

  22. Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA

    Anders M. Dale & Terry L. Jernigan

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  1. Erik Newman
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  2. Wesley K. Thompson
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  14. Linda Chang
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  15. Thomas M. Ernst
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  16. Jean A. Frazier
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  17. Jeffrey R. Gruen
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  22. Tal Kenet
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  23. Walter E. Kaufmann
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  26. Anders M. Dale
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  27. Terry L. Jernigan
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Correspondence to Erik Newman.

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Conflicts of interest

Jean A. Frazier has received research support from GlaxoSmithKline, Pfizer, Inc., Neuren, Roche, and Seaside Therapeutics, NICHD, NIMH, NINDS and has served on a Data Safety Monitoring Board for Forest Pharmaceuticals. Anders M. Dale is a founder of and holds equity interest in CorTechs Labs, La Jolla, CA and serves on its scientific advisory board. The terms of this arrangement have been reviewed and approved by UC San Diego, in accordance with its conflict of interest policies. All other authors reported no biomedical financial interests or potential conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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For the Pediatric Imaging, Neurocognition, and Genetics Study.

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Newman, E., Thompson, W.K., Bartsch, H. et al. Anxiety is related to indices of cortical maturation in typically develo** children and adolescents. Brain Struct Funct 221, 3013–3025 (2016). https://doi.org/10.1007/s00429-015-1085-9

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  • DOI: https://doi.org/10.1007/s00429-015-1085-9

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