Table 2.

Effects of gene variants

Gene variant	Gene product	Gene product function	Influence of variant	Primary brain regions of action	Physiologic effects
Dopamine system
COMT (Val158Met)	Catechol-o-methyltransferase	Degradation of catecholamines	Met variant- carriers have reduced COMT activity	Prefrontal Cortex	Differential dopaminergic signaling influences PFC function (COMT-genotype model), may explain different drug effects [58]
DRD4 (exon 3 VNTR)	Dopamine receptor D4	Dopaminergic transmission	7R-carriers have reduced DRD4 function	Prefrontal Cortex	Variation in dopaminergic signaling influences PFC function, interaction with other genotypes [25]
SLC6A3 (3′UTR VNTR); SLC6A3 (3′UTR VNTR/intron 8 VNTR haplotype)	Dopamine transporter	Reuptake of dopamine	9R- vs. 10R-carriers have reduced or increased DAT availability (inconsistent findings)	Striatum	Variability of striatal dopamine Transporter availability influences PFC function directly or indirectly via cortico-striatal pathways [24]
Serotonin system
TPH2 (e.g. rs4570625, rs11178997)	Tryptophan hydroxylase 2	Synthesis of serotonin	Influences transcriptional activity	Raphe nuclei, with ubiquitous action of serotonin	Differential activity of the cortico-limbic circuit
Others
NOS1 exon 1f-VNTR	Neuronal nitric oxide (NO) synthase	Synthesis of neuronal NO	Allelic variation in reporter gene expression	Striatum	NO function influences dopamine signaling [32]
LPHN3 (ADHD risk haplotype)	Latrophilin	Adhesion G-protein coupled receptor (?)	Decreased NAA/Cr ratio in risk haplotype carriers	Amygdala, caudate nucleus, cerebellum, and cerebral cortex	Possibly influences dopamine-glutamatergic system interaction

COMT, Catechol-o-methyltransferase; DAT, dopamine transporter; NAA/Cr, N-acetyl aspartate/creatine; NO, nitric oxide; PFC, prefrontal cortex; UTR, untranslated region; VNTR, variable number of tandem repeats.