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: Animal models; Basic studies; Endophenotypes; Normality and psychopathology continuum; RDoC; Translational research.

Fig. 1

The bottom-up and top-down model approach in experimental biology. The genotype-outcome interaction implies a dynamic functional network (right), which comprises the bottom-up and top-down directions, the most commonly used approaches to model pathological states (left).

Fig. 2

How The Triune brain and The Affective Neuroscience Scale corresponds to the RDoC system. According to the RDoC system, behavioural endophenotypes attribute 5 main behavioural domains. They are not only distinct but describe personality as an interacting and dynamic individual trait. The domains are objectively different, determined by particular neuronal networks. Separation of the networks is due to a distinction in the functions they serve (The Affective Neuroscience Scale, Panksepp, 1998). This distinction corresponds well with the concept of a gradual evolution of the brain (the triune brain model of MacLean, 1970).

Fig. 3

The “interacting domains” approach. The RDoC paradigm provides the opportunity to create a theoretical framework to decipher interactions between behavioural domains. For instance, the simplest interaction model might comprise 3 domains. Considering a possible hierarchy between domains, it can be predicted that only some integrations will serve healthy brain activity. Thus, negative and positive affect transition is subject to regulation by the cognitive systems domain. Pathology appears as a manifestation of aberrant crosstalk and disturbed hierarchy among the systems. Thus, prevalence of either positive or negative affects feeds back on the cognitive systems.