Cognitive Phenotypes for Biomarker Identification in Mental Illness: Forward and Reverse Translation

Psychiatric illness has been acknowledged for as long as people were able to describe behavioral abnormalities in the general population. In modern times, these descriptions have been codified and continuously updated into manuals by which clinicians can diagnose patients. None of these diagnostic manuals have attempted to tie abnormalities to neural dysfunction however, nor do they necessitate the quantification of cognitive function despite common knowledge of its ties to functional outcome. In fact, in recent years the National Institute of Mental Health released a novel transdiagnostic classification, the Research Domain Criteria (RDoC), which utilizes quantifiable behavioral abnormalities linked to neurophysiological processes. This reclassification highlights the utility of RDoC constructs as potential cognitive biomarkers of disease state. In addition, with RDoC and cognitive biomarkers, the onus of researchers utilizing animal models no longer necessitates the recreation of an entire disease state, but distinct processes. Here, we describe the utilization of constructs from the RDoC initiative to forward animal research on these cognitive and behavioral processes, agnostic of disease. By linking neural processes to these constructs, identifying putative abnormalities in diseased patients, more targeted therapeutics can be developed.