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

Erik Newman; Wesley K Thompson; Hauke Bartsch; Donald J Hagler Jr; Chi-Hua Chen; Timothy T Brown; Joshua M Kuperman; Connor McCabe; Yoonho Chung; Ondrej Libiger; Natacha Akshoomoff; Cinnamon S Bloss; B J Casey; Linda Chang; Thomas M Ernst; Jean A Frazier; Jeffrey R Gruen; David N Kennedy; Sarah S Murray; Elizabeth R Sowell; Nicholas Schork; Tal Kenet; Walter E Kaufmann; Stewart Mostofsky; David G Amaral; Anders M Dale; Terry L Jernigan

doi:10.1007/s00429-015-1085-9

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

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

Authors

Erik Newman^{1

2}, Wesley K Thompson^{3

4}, Hauke Bartsch⁵, Donald J Hagler Jr^{5

6}, Chi-Hua Chen^{3

5}, Timothy T Brown^{5

7}, Joshua M Kuperman^{5

6}, Connor McCabe^{8

9}, Yoonho Chung^{8

5

10}, Ondrej Libiger¹¹, Natacha Akshoomoff^{8

3}, Cinnamon S Bloss¹¹, B J Casey¹², Linda Chang¹³, Thomas M Ernst¹³, Jean A Frazier¹⁴, Jeffrey R Gruen^{15

16}, David N Kennedy¹⁴, Sarah S Murray¹⁷, Elizabeth R Sowell^{18

19}, Nicholas Schork¹¹, Tal Kenet²⁰, Walter E Kaufmann²¹, Stewart Mostofsky²², David G Amaral²³, Anders M Dale^{5

6

7

24}, Terry L Jernigan^{8

3

6

24}

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Age Factors
Anxiety / epidemiology
Anxiety / pathology*
Anxiety Disorders / epidemiology
Anxiety Disorders / pathology*
Child
Diffusion Magnetic Resonance Imaging
Female
Humans
Male
Prefrontal Cortex / growth & development*
Prefrontal Cortex / pathology*
Psychiatric Status Rating Scales
Risk Factors
Self Report
Sex Factors
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding