Impaired Executive Control Is Associated with a Variation in the Promoter Region of the Tryptophan Hydroxylase 2 Gene

Current models of attention describe attention not as a homogenous entity but as a set of neural networks whose measurement yields a set of three endophenotypes—alerting, orienting, and executive control. Previous findings revealed different neuroanatomical regions for these subsystems, and data from twin studies indicate differences in their heritability. The present study investigated the molecular genetic basis of attention in a sample of 100 healthy subjects. Attention performance was assessed with the attention network test that distinguishes alerting, orienting, and executive control (conflict) using a simple reaction time paradigm with different cues and congruent and incongruent flankers. Two gene loci on candidate genes for cognitive functioning, the functional catechol-
O
-methyltransferase (
COMT
) VAL158MET and the tryptophan hydroxylase 2 (
TPH2
) −703 G/T promoter polymorphism, were tested for possible associations with attention.
COMT
is involved in the catabolism of dopamine, and
TPH
is the rate-limiting enzyme for serotonin synthesis. Results showed no effect of the
COMT
polymorphism on attention performance. However, the TT genotype of
TPH2
−03 G/T was significantly associated with more errors (a possible indicator of impaired impulse control;
p
= .001) and with decreased performance in executive control (
p
= .001). This single-nucleotide polymorphism on the
TPH2
gene explained more than 10% of the variance in both indicators of attention stressing the role of the serotonergic system for cognitive functions.