Understanding Reward Dysfunction in Bipolar Affective Disorder through Behavioural, Cognitive and Neurobiological Changes

Bipolar disorder, like many neuropsychiatric conditions, can be studied from a number of perspectives; from observation of behaviour, to study of cognitive dysfunction, through to changes at the molecular and genetic level. A consequence of this way of working is that there is inadequate communication between different levels of analysis, such that insufficient thought is given to whether a theoretical model derived from behavioural work fits with neurobiological data, and vice versa. Such limitations represent a key limiting factor in successful translation. Therefore, this paper takes a dominant theoretical model of bipolar disorder, based on that by Gray (1994) and developed by Alloy et al., (2015) as a basis to propose that the foundational pathology in bipolar is reward hypersensitivity, and to review how recent diverse neurobiological, cognitive and behavioural findings fit with this understanding. Executive Function deficits, partially derived from heritable structural changes are suggested as a foundation through which reward hypersensitivity develops to disorder, and CANA1C polymorphism-induced hyperactivity, further serves to drive the system towards reward seeking goals, through interaction with dopaminergic systems. This action is supplemented by a genetic predisposition for cognitive regulatory dysfunction, leading to improper modulation of emotive and reward networks. Specifically, deficits in top-down limbic modulation leads to behaviours disproportionally driven by limbic and reward circuitry; this pathology strengths over time through use. This therefore eventually results in substantial regional disconnect, reflected in epigenetic changes to neurotransmitters and observable histological changes.