Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene.
The ability to inhibit a response is an important component of normal behavioral control and is an aspect of psychopathology when diminished. Converging evidence implicates the serotonergic neurotransmitter system in response inhibition circuitry.


OBJECTIVE
The present study examined potential associations between serotonergic genetic markers and response inhibition as indexed by Stop Task performance.


METHODS
College-age participants (N=199) completed self-report questionnaires, the computerized Stop Task, and donated buccal cells for genetic analyses. Statistics were analyzed by ANOVA.


RESULTS
Stop Signal reaction time was not associated with allelic variation at a monoamine oxidase A promoter length polymorphism or a serotonin 1B terminal autoreceptor polymorphism (G861C). An intronic genetic marker of the neuronal tryptophan hydroxylase-2 (the rate-limiting enzyme for serotonin biosynthesis) gene, however, was associated with the Stop Signal reaction time. Individuals homozygous for the T variant at an intron-8 polymorphism had the longest Stop Signal reaction time (i.e. greater impulsivity, P=0.01), and this effect was stronger in males (P=0.01) than in females (P=0.10).


CONCLUSIONS
A genotype at an intron-8 tryptophan hydroxylase-2 polymorphism was associated with response inhibition as indexed by the Stop Task. These results, if replicated, would implicate dorsal raphe serotonin neurons in response inhibition. It may be that individuals with the T/T genotype may have reduced tryptophan hydroxylase-2 function and correspondingly lower central serotonin levels; however, further investigation of the reported association is required.
Stoltenberg
Scott F
SF
Department of Psychology, Black Hills State University, Spearfish, South Dakota 57799, USA. ScottStoltenberg@bhsu.edu
Glass
Jennifer M
JM
Chermack
Steven T
ST
Flynn
Heather A
HA
Li
Sheng
S
Weston
Margaret E
ME
Burmeister
Margit
M
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D001483:Base Sequence; D001921:Brain / Q000201:enzymology*; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011930:Reaction Time; D012701:Serotonin / Q000096:biosynthesis; D011795:Surveys and Questionnaires; D013647:Task Performance and Analysis; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D012701:Serotonin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase