Title:The Role of Catechol-O-Methyltransferase in Reward Processing and Addiction
VOLUME: 11 ISSUE: 3
Author(s):E. M. Tunbridge, A. Huber, S. M. Farrell, K. Stumpenhorst, P. J. Harrison and M. E. Walton
Affiliation:University Department of Psychiatry, Warneford Hospital, Oxford, OX3 7JX, UK.
Keywords:Dopamine, COMT, prediction error, nucleus accumbens, striatum, smoking, Catechol O Methyl Transferase, Prefrontal cortex, COMT gene, Orbitofrontal cortex, valine
Abstract:Catechol-O-methyltransferase (COMT) catabolises dopamine and is important for regulating dopamine levels
in the prefrontal cortex. Consistent with its regulation of prefrontal cortex dopamine, COMT modulates working memory
and executive function; however, its significance for other cognitive domains, and in other brain regions, remains
relatively unexplored. One such example is reward processing, for which dopamine is a critical mediator, and in which the
striatum and corticostriatal circuitry are implicated. Here, we discuss emerging data which links COMT to reward
processing, review what is known of the underlying neural substrates, and consider whether COMT is a good therapeutic
target for treating addiction. Although a limited number of studies have investigated COMT and reward processing,
common findings are beginning to emerge. COMT appears to modulate cortical and striatal activation during both reward
anticipation and delivery, and to impact on reward-related learning and its underlying neural circuitry. COMT has been
studied as a candidate gene for numerous reward-related phenotypes and there is some preliminary evidence linking it
with certain aspects of addiction. However, additional studies are required before these associations can be considered
robust. It is premature to consider COMT a good therapeutic target for addiction, but this hypothesis should be revisited as
further information emerges. In particular, it will be critical to reveal the precise neurobiological mechanisms underlying
links between COMT and reward processing, and the extent to which these relate to the putative associations with
addiction.
