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Brain Struct Funct. 2016 Jul;221(6):3013-25. doi: 10.1007/s00429-015-1085-9. Epub 2015 Jul 17.

Anxiety is related to indices of cortical maturation in typically developing children and adolescents.

Author information

1
Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA. enewman@ucsd.edu.
2
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. enewman@ucsd.edu.
3
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
4
Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
5
Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.
6
Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
7
Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
8
Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA.
9
Department of Psychology, University of Washington, Seattle, WA, USA.
10
Department of Psychology, Yale University, New Haven, CT, USA.
11
Scripps Genomic Medicine, Scripps Translational Science Institute and Scripps Health, La Jolla, CA, USA.
12
Sackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY, USA.
13
Department of Medicine, University of Hawaii and Queen's Medical Center, Honolulu, HI, USA.
14
Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, USA.
15
Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
16
Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
17
Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
18
Department of Pediatrics, University of Southern California, Los Angeles, CA, USA.
19
Children's Hospital, Los Angeles, CA, USA.
20
Department of Neurology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
21
Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
22
Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA.
23
Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA, USA.
24
Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.

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.

KEYWORDS:

Anxiety; Brain development; Cortical surface area; Cortical thickness; Magnetic resonance imaging; Ventromedial prefrontal cortex

PMID:
26183468
PMCID:
PMC5064818
DOI:
10.1007/s00429-015-1085-9
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

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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