Animal models in psychiatric research: The RDoC system as a new framework for endophenotype-oriented translational neuroscience

Abstract

The recently proposed Research Domain Criteria (RDoC) system defines psychopathologies as phenomena of multilevel neurobiological existence and assigns them to 5 behavioural domains characterizing a brain in action. We performed an analysis on this contemporary concept of psychopathologies in respect to a brain phylogeny and biological substrates of psychiatric diseases. We found that the RDoC system uses biological determinism to explain the pathogenesis of distinct psychiatric symptoms and emphasises exploration of endophenotypes but not of complex diseases. Therefore, as a possible framework for experimental studies it allows one to evade a major challenge of translational studies of strict disease-to-model correspondence. The system conforms with the concept of a normality and pathology continuum, therefore, supports basic studies. The units of analysis of the RDoC system appear as a novel matrix for model validation. The general regulation and arousal, positive valence, negative valence, and social interactions behavioural domains of the RDoC system show basic construct, network, and phenomenological homologies between human and experimental animals. The nature and complexity of the cognitive behavioural domain of the RDoC system deserve further clarification. These homologies in the 4 domains justifies the validity, reliably and translatability of animal models appearing as endophenotypes of the negative and positive affect, social interaction and general regulation and arousal systems’ dysfunction. Keywords: RDoC, Translational research, Animal models, Endophenotypes, Basic studies, Normality and psychopathology continuum