Anxiety is related to indices of cortical maturation in typically developing children and adolescents
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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.
KeywordsAnxiety Brain development Cortical surface area Cortical thickness Magnetic resonance imaging Ventromedial prefrontal cortex
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://pingstudy.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.
Compliance with ethical standards
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.
Research involving human participants
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.
Informed consent was obtained from all individual participants included in the study.
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