Neuropsychological Characterization of Aggressive Behavior in Children and Adolescents with CD/ODD and Effects of Single Doses of Medications: The Protocol of the Matrics_WP6-1 Study

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.

Disruptive Behavior Disorders: Symptoms, Evaluation and Treatment

“…Though DBD is among the most common reasons for referral to youth mental health services, the efficacy of therapeutic interventions in clinical practice still remains somewhat unclear. To define more appropriate targets for novel pharmacological treatments for DBD, Balia and collaborators [ 8 ], together with the European Commission within the Seventh Framework Program, here proposed the protocol for a multicenter case-control study which will be followed by a single-blind, placebo-controlled, cross-over, randomized acute single-dose medication challenge. This study is part of a larger program aimed to identify the neural, genetic, and molecular underpinnings of aggression and antisocial behaviors in preclinical models and clinical samples, known as the Multidisciplinary Approaches to Translational Research in Conduct Syndromes (MATRICS) project.…”

“… Italy Suor Orsola Benincasa University, University of Campania “Luigi Vanvitelli”, Federico II University, Santobono-Pausilipon Children Hospital, IRCCS Stella Maris Foundation Article [ 4 ] López-Romero L, Cutrín O, Maneiro L, Domínguez-Álvarez B, Romero E. Spain, Netherlands Universidade de Santiago de Compostela, Leiden University Article [ 5 ] Smorti M, Inguaggiato E, Vezzosi L, Milone A. Italy University of Pisa, IRCCS Stella Maris Foundation Article [ 6 ] Marzilli E, Cerniglia L, Cimino S. Italy University of Rome “La Sapienza”, International Telematic University Uninettuno Article [ 7 ] Fantozzi P, Sesso G, Muratori P, Milone A, Masi G. Italy IRCCS Stella Maris Foundation, University of Pisa Systematic Review [ 8 ] Balia C, Carucci S, Milone A, Romaniello R, Valente E, Donno F, Montesanto A, Brovedani P, Masi G, Glennon JC, Coghill D, Zuddas A, The Matrics Consortium. Italy, Ireland, Netherlands, Australia University of Cagliari, “Cao” Pediatric Hospital, ARNAS “Brotzu” Hospital Trust, IRCCS Stella Maris Foundation, University College Dublin, Radboud University, University of Dundee, Murdoch Children’s Research Institute of Melbourne, University of Melbourne Study Protocol [ 9 ] Lochman JE, Boxmeyer CL, Bui C, Hakim E, Jones S, Kassing F, McDonald K, Powell N, Qu L, Dishion T. US...…”