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Cortex. 2019 Sep 19;121:135-146. doi: 10.1016/j.cortex.2019.08.017. [Epub ahead of print]

Distinct associations between fronto-striatal glutamate concentrations and callous-unemotional traits and proactive aggression in disruptive behavior.

Author information

1
Department of Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom. National Autism Unit (NAU), SLaM NHS Foundation Trust, London, UK.
2
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, the Netherlands; Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, the Netherlands.
3
Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, the Netherlands.
4
University of Groningen, University Medical Center Groningen, Department of Child and Adolescent Psychiatry, Groningen, the Netherlands.
5
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
6
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
7
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
8
Department of Child and Adolescent Psychiatry and Psychology, Clínic Institute of Neurosciences, Hospital Clínic de Barcelona, 2017SGR881, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spain, Universitat de Barcelona, Spain.
9
Child and Adolescent Psychiatry Department, Hospital General Universitario Gregorio Maranon, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
10
Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital, University of Ulm, Ulm, Germany.
11
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, the Netherlands.
12
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Human Genetics, Nijmegen, the Netherlands; Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Department of Psychiatry, Nijmegen, the Netherlands.
13
Department of Child and Adolescent Psychiatry, King's College London, London, UK; Centre for Interventional Paediatric Psychopharmacology and Rare Diseases, South London and Maudsley NHS Foundation Trust, London, UK.
14
Department of Child and Adolescent Psychiatry, King's College London, London, UK.
15
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
16
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center, Nijmegen, the Netherlands.
17
Department of Neuroimaging, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, United Kingdom.
18
Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, Nijmegen, the Netherlands; Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, the Netherlands. Electronic address: j.naaijen@donders.ru.nl.

Abstract

Disruptive behavior is associated with societally and personally problematic levels of aggression and has been linked to abnormal structure and function of fronto-amygdala-striatal regions. Abnormal glutamatergic signalling within this network may play a role in aggression. However, disruptive behavior does not represent a homogeneous construct, but can be fractionated across several dimensions. Of particular interest, callous-unemotional (CU) traits have been shown to modulate the severity, neural and behavioural characterisation, and therapeutic outcomes of disruptive behaviour disorders (DBDs) and aggression. Further, individuals showing disruptive behavior differ to the extent that they engage in subtypes of aggression (i.e., proactive [PA] and reactive aggression [RA]) which may also represent distinct therapeutic targets. Here we investigated how glutamate signalling within the fronto-amygdala-striatal circuitry was altered along these dimensions in youths showing disruptive behavior (n = 140) and typically developing controls (TD, n = 93) within the age-range of 8-18 years. We used proton magnetic resonance spectroscopy (1H-MRS) in the anterior cingulate cortex (ACC), striatum, amygdala and insula and associated glutamate concentrations with continuous measures of aggression and CU-traits using linear mixed-effects models. We found evidence of a dissociation for the different measures and glutamate concentrations. CU traits were associated with increased ACC glutamate ('callousness': b = .19, t (108) = 2.63, p = .01, r = .25; 'uncaring': b = .18, t (108) = 2.59, p = .011, r = .24) while PA was associated with decreased striatal glutamate concentration (b = -.23, t (28) = -3.02, p = .005, r = .50). These findings suggest dissociable correlates of CU traits and PA in DBDs, and indicate that the ACC and striatal glutamate may represent novel pharmacological targets in treating these different aspects.

KEYWORDS:

Aggression; Anterior cingulate cortex; Callous unemotional traits; Glutamate; Magnetic resonance spectroscopy

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