Further support for a role of the His452Tyr variant in 5-HT2A receptor gene in memory functions in humans

Abstract

Wagner et al. (2008) recently published a brief report in the International Journal of Neuropsychopharmacology , which replicated the previous findings of de Quervain et al. (2003) and indicated that the functional 5-HT2A receptor variant, His452Tyr (rs6314), is associated with episodic long-term memory in humans. There is considerable evidence from studies in animals and humans that serotonin is pivotally implicated in learning and memory (e.g. Buhot, 1997). The tyrosine (Tyr) allele of the His452Tyr variant in the human 5-HT2A receptor is associated with blunted receptor response upon serotonin stimulation (Ozaki et al. 1997) with effects on intracellular calcium levels and protein kinase-A phosphorylation, both of which are important for memory formation at the cellular level. This would influence performance on memory tasks, as has been shown for pharmacological manipulation of serotonin receptors (Meneses, 2007). Wagner et al. (2008) compared 113 His/His carriers to 20 His/Tyr carriers on a variety of cognitive tests. They hypothesized that the His/Tyr group would manifest poorer performance on long-term recall and recognition tasks. To test the discriminant validity of the variant (i.e. that the variant is specifically related to long-term episodic memory functions and not to other cognitive functions), Wagner et al. (2008) also tested performance differences between the groups on tasks measuring short-term memory, attention and executive functions. The results showed that the His/Tyr group recognized and recalled fewer words than the His/His group on an auditory, free recall, learning task with a 30-min retention interval between learning phase and test phase. There was no similar pattern of difference for tasks measuring attention and executive functioning. We obtained further data on the association between the 5-HT2A receptor His452Tyr variant and memory function from the ‘Why Do Young Women Smoke?’ (WDYWS) project, a study ongoing …