Sex Differences in Trace Amine-Associated Receptor Signalling

Most TAAR-related drug discovery research which has advanced to clinical trials has focused on neuropsychiatric disease. Unfortunately, most studies are either conducted on males only or male and female data are not presented separately to inform on sex specificity of findings. As sex bias is highly prevalent in neuropsychiatric disease, this relative lack of considering sex as a potential confounding factor in these studies hampers complete elucidation of mechanisms at play. Therefore, in this chapter, we focus on the three TAARs for which most research data have been generated (TAAR1, TAAR5 and TAAR8) and summarise sex differences that have been reported in terms of TAAR expression and/or function, with consideration of species differences. In addition, given the sparsity of this information, we expanded our literature search to also include a discussion of role players at different levels of the trace amine signalling pathways - e.g. TAAR ligands. The role of oestrogen as potential TAAR modulator is also discussed. Integrating this information, we provide a critical discussion on whether significant sex differences are likely to exist in TAAR signalling. Finally, we make recommendations on research priorities going forward to ensure that TAAR-focused therapeutics development research is equally beneficial to both males and females.