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Prefrontal executive function and D1, D3, 5-HT2A and 5-HT6 receptor gene variations in healthy adults
Hsien-Yuan Lane1, Yi-Ching Liu, Chieh-Liang Huang
1Department of Psychiatry, Institute of Clinical Medical Science, China Medical University and Hospital, Taichung, Taiwan. hylane@gmail.com
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.
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