Dopamine and Working Memory: Genetic Variation, Stress and Implications for Mental Health

At the molecular level, the neurotransmitter dopamine (DA) is a key regulatory component of executive function in the prefrontal cortex (PFC) and dysfunction in dopaminergic (DAergic) circuitry has been shown to result in impaired working memory (WM). Research has identified multiple common genetic variants suggested to impact on the DA system functionally and also behaviourally to alter WM task performance. In addition, environmental stressors impact on DAergic tone, and this may be one mechanism by which stressors confer vulnerability to the development of neuropsychiatric conditions. This chapter aims to evaluate the impact of key DAergic gene variants suggested to impact on both synaptic DA levels (COMT, DAT1, DBH, MAOA) and DA receptor function (ANKK1, DRD2, DRD4) in terms of their influence on visuospatial WM. The role of stressors and interaction with the genetic background is discussed in addition to discussion around some of the implications for precision psychiatry. This and future work in this area aim to disentangle the neural mechanisms underlying susceptibility to stress and their impact and relationship with cognitive processes known to influence mental health vulnerability.