title: Anxiety is related to indices of cortical maturation in typically developing children and adolescents.
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.
authors.affiliation: Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA. enewman@ucsd.edu.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA. enewman@ucsd.edu.
authors.forename: Erik
authors.initials: E
authors.lastname: Newman
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.|Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Hauke
authors.initials: H
authors.lastname: Bartsch
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.|Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.|Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.|Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Brown
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.|Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Kuperman
authors.affiliation: Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA.|Department of Psychology, University of Washington, Seattle, WA, USA.
authors.forename: Connor
authors.initials: C
authors.lastname: McCabe
authors.affiliation: Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA.|Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.|Department of Psychology, Yale University, New Haven, CT, USA.
authors.forename: Yoonho
authors.initials: Y
authors.lastname: Chung
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute and Scripps Health, La Jolla, CA, USA.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Libiger
authors.affiliation: Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Akshoomoff
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute and Scripps Health, La Jolla, CA, USA.
authors.forename: Cinnamon S
authors.initials: CS
authors.lastname: Bloss
authors.affiliation: Sackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Casey
authors.affiliation: Department of Medicine, University of Hawaii and Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of Medicine, University of Hawaii and Queen's Medical Center, Honolulu, HI, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ernst
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: Jean A
authors.initials: JA
authors.lastname: Frazier
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.|Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gruen
authors.affiliation: Department of Psychiatry, University of Massachusetts Medical School, Boston, MA, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Kennedy
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Murray
authors.affiliation: Department of Pediatrics, University of Southern California, Los Angeles, CA, USA.|Children's Hospital, Los Angeles, CA, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sowell
authors.affiliation: Scripps Genomic Medicine, Scripps Translational Science Institute and Scripps Health, La Jolla, CA, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schork
authors.affiliation: Department of Neurology and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Tal
authors.initials: T
authors.lastname: Kenet
authors.affiliation: Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Kaufmann
authors.affiliation: Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Stewart
authors.initials: S
authors.lastname: Mostofsky
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California, Davis, Davis, CA, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Amaral
authors.affiliation: Multimodal Imaging Laboratory, University of California, San Diego, La Jolla, CA, USA.|Department of Radiology, University of California, San Diego, La Jolla, CA, USA.|Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.|Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Center for Human Development, University of California, San Diego, 9500 Gilman Drive, MC 0115, La Jolla, CA, 92093, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.|Department of Radiology, University of California, San Diego, La Jolla, CA, USA.|Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Jernigan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001007:Anxiety / Q000453:epidemiology / Q000473:pathology*; D001008:Anxiety Disorders / Q000453:epidemiology / Q000473:pathology*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000254:growth & development* / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D057566:Self Report; D012737:Sex Factors; D055815:Young Adult
keywords: Anxiety; Brain development; Cortical surface area; Cortical thickness; Magnetic resonance imaging; Ventromedial prefrontal cortex