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.


CONCLUSIONS
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.
Lane
Hsien-Yuan
HY
Department of Psychiatry, Institute of Clinical Medical Science, China Medical University and Hospital, Taichung, Taiwan. hylane@gmail.com
Liu
Yi-Ching
YC
Huang
Chieh-Liang
CL
Hsieh
Ching-Liang
CL
Chang
Yi-Lin
YL
Chang
Lauren
L
Chang
Yue-Cune
YC
Chang
Wen-Ho
WH
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D017397:Prefrontal Cortex / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D011985:Receptors, Serotonin / Q000235:genetics*
D017931:DNA Primers; D044402:Receptor, Serotonin, 5-HT2A; D017447:Receptors, Dopamine D1; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor