Citation

Craig MC, Mulder LM, Zwiers MP, Sethi A, Hoekstra PJ, Dietrich A, Baumeister S, Aggensteiner PM, Banaschewski T, Brandeis D, Werhahn JE, Walitza S, Castro-Fornieles J, Arango C, Schulze UME, Glennon JC, Franke B, Santosh PJ, Mastroianni M, van Asten JJA, Buitelaar JK, Lythgoe DJ, Naaijen J. Cortex 2019; 121: 135-146.

Affiliation

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.

Copyright

(Copyright © 2019, Masson Editeur)

DOI

10.1016/j.cortex.2019.08.017

PMID

31622899

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.

Copyright © 2019 Elsevier Ltd. All rights reserved.

Language: en

Keywords

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