Conduct Disorder (CD) is the key paediatric disorder characterized by severe aggression. It is heterogeneous, and our understanding of the neurobiology to subtype aggression is limited. MATRICS is a multidisciplinary consortium of academic partners and SMEs that focuses on the subtyping of aggression both within CD and of the broader cross-disorder trait of aggression. MATRICS will test the hypothesis that reactive and instrumental aggression result from aberrant autonomic reactivity coupled to the differential impairment of three basic neural functions: 1) regulation of control mechanisms of aggression, 2) emotional value rating of others, and 3) empathy and moral decision making. MATRICS will employ the same psychological tasks assessing 1), 2) and 3) in animal aggression models and human CD samples concurrent with the assessment of neural, neurochemical, (epi)-genetic and autonomic nervous system markers. These data will be integrated with matching expression profiling from neurons derived from CD IPSCs. MATRICS also examines how environmental risks, whether or not they interact with genetic factors, are translated in epigenetic and neural changes. MATRICS will data-mine existing large integrated imaging-genetics cohorts (NeuroIMAGE; IMAGEN) and prospective cohorts (TRAILS; ALSPAC) with follow-up into adulthood and the (epi)genetic profiling of the PERS CD cohort, and collect a large new CD cohort and controls for collection of MRI, (epi)-genetic, biochemical and environmental measures. Bayesian machine learning tools will integrate multi-source and multi-level data, and generate predictive algorithms of persistent aggression into adulthood. MATRICS will identify new potentially ‘druggable’ targets, develop novel animal models and conduct pilot medication and neuro/biofeedback studies in high-risk and CD patients. MATRICS builds on existing fruitful EU collaborations which maximises feasibility and successful output.
Call for proposal
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Funding SchemeCP-FP - Small or medium-scale focused research project
6525 EC Nijmegen