Prefrontal executive function and D₁, D₃, 5-HT2A and 5-HT₆ receptor gene variations in healthy adults

Objective: The Val158Met polymorphism of the catechol-O-methyltransferase gene has been demonstrated to be associated with prefrontal executive function explaining 4% of variance in perseverative errors on the Wisconsin Card Sorting Test (WCST). Studies suggest that dopamine D 1 and D 3 and serotonin 5-HT 2A and 5-HT 6 receptors may also be involved in prefrontal cognitive function and that genetic polymorphisms (D 1 A-48G, D 3 Ser9Gly, 5-HT 2A T102C, and 5-HT 6 T267C) of these receptors may be associated with brain glucose metabolism or neurophysiological function. The current study’s objective was to investigate whether executive function varies with these genetic variations. Methods: A sample of 216 healthy Han Chinese adults were measured with the WCST and genotyped for the 4 genetic polymorphisms. Results: Kruskal–Wallis tests showed a significant difference in WCST perseverative errors among the genotypes D 3 Ser9Gly ( p = 0.009), 5-HT 2A T102C ( p = 0.038) and 5-HT 6 T267C ( p = 0.010), but not in the genotype D 1 A-48G. Multiple regression analysis for the WCST natural logarithm values (i.e., for fulfilling the normal distribution requirement) showed that subjects’ perseverative errors were significantly influenced by D 1 A-48G, D 3 Ser9Gly, 5-HT 2A T102C and 5-HT 6 T267C polymorphisms after adjustment of other variables. Conclusion: The preliminary data suggest that D 1 , D 3 , 5-HT 2A and 5-HT 6 genetic mutations may influence prefrontal executive cognition in healthy adults. Further studies in larger samples with other ethnicities or in mentally ill patients are warranted.