title: Neural Correlates of Aggression in Medication-Naive Children with ADHD: Multivariate Analysis of Morphometry and Tractography.
abstract: Aggression is widely observed in children with attention deficit/hyperactivity disorder (ADHD) and has been frequently linked to frustration or the unsatisfied anticipation of reward. Although animal studies and human functional neuroimaging implicate altered reward processing in aggressive behaviors, no previous studies have documented the relationship between fronto-accumbal circuitry-a critical cortical pathway to subcortical limbic regions-and aggression in medication-naive children with ADHD. To address this, we collected behavioral measures and parental reports of aggression and impulsivity, as well as structural and diffusion MRI, from 30 children with ADHD and 31 healthy controls (HC) (mean age, 10±2.1 SD). Using grey matter morphometry and probabilistic tractography combined with multivariate statistical modeling (partial least squares regression and support vector regression), we identified anomalies within the fronto-accumbal circuit in childhood ADHD, which were associated with increased aggression. More specifically, children with ADHD showed reduced right accumbal volumes and frontal-accumbal white matter connectivity compared with HC. The magnitude of the accumbal volume reductions within the ADHD group was significantly correlated with increased aggression, an effect mediated by the relationship between the accumbal volume and impulsivity. Furthermore, aggression, but not impulsivity, was significantly explained by multivariate measures of fronto-accumbal white matter connectivity and cortical thickness within the orbitofrontal cortex. Our multi-modal imaging, combined with multivariate statistical modeling, indicates that the fronto-accumbal circuit is an important substrate of aggression in children with ADHD. These findings suggest that strategies aimed at probing the fronto-accumbal circuit may be beneficial for the treatment of aggressive behaviors in childhood ADHD.
authors: Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA.
authors: Jiook
authors: 0000000253147992
authors: J
authors: Cha
authors: Laboratory for Perceptual Dynamics, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium.
authors: Tomer
authors: T
authors: Fekete
authors: Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA.
authors: Francesco
authors: F
authors: Siciliano
authors: Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA.
authors: Dominik
authors: D
authors: Biezonski
authors: Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA.
authors: Laurence
authors: L
authors: Greenhill
authors: Department of Psychiatry, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors: Steven R
authors: SR
authors: Pliszka
authors: Department of Psychiatry, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors: Joseph C
authors: JC
authors: Blader
authors: Department of Psychology, Fordham University, New York, NY, USA.
authors: Amy Krain
authors: AK
authors: Roy
authors: National Institute of Mental Health, Bethesda, MD, USA.
authors: Ellen
authors: E
authors: Leibenluft
authors: Department of Psychiatry, Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute, New York, NY, USA.
authors: Jonathan
authors: J
authors: Posner
mesh_terms: D000293:Adolescent; D000374:Aggression / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000473:pathology* / Q000503:physiopathology*; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D002648:Child; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007175:Impulsive Behavior / Q000502:physiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D009434:Neural Pathways / Q000503:physiopathology; D013223:Statistics as Topic; D066127:White Matter / Q000473:pathology
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