The Importance of a Multidimensional Approach to the Preclinical Study of Major Depressive Disorder and Apathy

Both the neuropsychiatric syndrome of apathy and major depressive disorder comprise a heterogenous cluster of symptoms which span multiple behavioural domains. Despite this heterogeneity, there is a tendency in the preclinical literature to conclude a MDD or apathy-like phenotype from a single dimensional behavioural task used in isolation, which may lead to inaccurate phenotypic interpretation. This is significant, as apathy and major depressive disorder are clinically distinct with different underlying mechanisms and treatment approaches. At the clinical level, apathy and major depressive disorder can be dissociated in the negative valence (loss) domain of the Research Domain Criteria. Symptoms of MDD in the negative valence (loss) domain can include an exaggerated response to emotionally salient stimuli and low mood, while in contrast apathy is characterised by an emotionally blunted state. In this article, we highlight how using a single dimensional approach can limit psychiatric model interpretation. We discuss how integrating behavioural findings from both the positive and negative (loss) valence domains of the Research Domain Criteria can benefit interpretation of findings. We focus particularly on behaviours relating to the negative valence (loss) domain, which may be used to distinguish between apathy and major depressive disorder at the preclinical level. Finally, we consider how future approaches using home cage monitoring may offer a new opportunity to detect distinct behavioural profiles and benefit the overall translatability of findings.