Citation

Balia C, Carucci S, Milone A, Romaniello R, Valente E, Donno F, Montesanto A, Brovedani P, Masi G, Glennon JC, Coghill D, Zuddas A, Consortium TM. Brain Sci. 2021; 11(12).

Copyright

(Copyright © 2021, Switzerland Molecular Diversity Preservation International (MDPI) AG)

DOI

10.3390/brainsci11121639

PMID

34942941

Abstract

Aggressive behaviors and disruptive/conduct disorders are some of the commonest reasons for referral to youth mental health services; nevertheless, the efficacy of therapeutic interventions in real-world clinical practice remains unclear. In order to define more appropriate targets for innovative pharmacological therapies for disruptive/conduct disorders, the European Commission within the Seventh Framework Programme (FP7) funded the MATRICS project (Multidisciplinary Approaches to Translational Research in Conduct Syndromes) to identify neural, genetic, and molecular factors underpinning the pathogenesis of aggression/antisocial behavior in preclinical models and clinical samples. Within the program, a multicentre case-control study, followed by a single-blind, placebo-controlled, cross-over, randomized acute single-dose medication challenge, was conducted at two Italian sites. Aggressive children and adolescents with conduct disorder (CD) or oppositional defiant disorder (ODD) were compared to the same age (10-17 y) typically developing controls (TDC) on a neuropsychological tasks battery that included both "cold" (e.g., inhibitory control, decision making) and "hot" executive functions (e.g., moral judgment, emotion processing, risk assessment). Selected autonomic measures (heart rate variability, skin conductance, salivary cortisol) were recorded before/during/after neuropsychological testing sessions. The acute response to different drugs (methylphenidate/atomoxetine, risperidone/aripiprazole, or placebo) was also examined in the ODD/CD cohort in order to identify potential neuropsychological/physiological mechanisms underlying aggression. The paper describes the protocol of the clinical MATRICS WP6-1 study, its rationale, the specific outcome measures, and their implications for a precision medicine approach.

Language: en

Keywords

aggression; callous-unemotional traits; acute placebo-controlled single-blind challenge clinical trial; ADHD medications; autonomic functioning; conduct disorder; control design; D2 receptor modulators; medications for aggression; neuropsychological functioning; oppositional defiant disorder