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J Am Acad Child Adolesc Psychiatry. 2019 Apr 17. pii: S0890-8567(19)30261-8. doi: 10.1016/j.jaac.2019.01.021. [Epub ahead of print]

Neuroimaging Evidence for Right Orbitofrontal Cortex Differences in Adolescents With Emotional and Behavioral Dysregulation.

Author information

1
University of Vermont, Burlington; Vermont Center on Behavior and Health, University of Vermont, Burlington. Electronic address: philip.spechler@uvm.edu.
2
University of Vermont, Burlington; Vermont Center on Behavior and Health, University of Vermont, Burlington.
3
University of Vermont, Burlington.
4
Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
5
School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland.
6
University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
7
Centre for Population Neuroscience and Stratified Medicine (PONS) and MRC-SGDP Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.
8
Universite de Montreal, CHU Ste Justine Hospital, Canada.
9
Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; School of Social Sciences, University of Mannheim, Mannheim, Germany.
10
NeuroSpin, CEA, Université Paris-Saclay, France.
11
Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, UK.
12
Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Germany.
13
Physikalisch-Technische Bundesanstalt (PTB), Berlin, Germany.
14
Institut National de la Santé et de la Recherche Médicale, INSERM Unit 1000 "Neuroimaging & Psychiatry", University Paris Sud - University Paris Saclay, France.
15
University Medical Centre Göttingen, Germany, and the Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Austria.
16
Technische Universität Dresden, Germany.
17
School of Psychology and Global Brain Health Institute, Trinity College Dublin, Ireland.

Abstract

OBJECTIVE:

To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype.

METHOD:

Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties ("dysregulated"; n = 233) who were compared to a matched sample from a low symptom class (controls, n = 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation.

RESULTS:

Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p < .05; k = 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F1,429 = 7.53, p < .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature.

CONCLUSION:

A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control.

KEYWORDS:

SDQ; VBM; adolescence; dysregulation; orbitofrontal cortex

PMID:
31004740
DOI:
10.1016/j.jaac.2019.01.021

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