Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder.
Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and allelic variations at the TPH1 locus have been implicated in the pathophysiology of depression. Using 1.5-Tesla functional magnetic resonance imaging, we investigated the possible relationship between TPH1 A218C polymorphism and amygdala response to negative facial stimuli in 26 right-handed female subjects with major depressive disorder (MDD). Genotyping was performed with the polymerase chain reaction. We found a significant association between A allele of the TPH1 A218C polymorphism and neural activations in response to negative facial stimuli. Subjects with the A allele of the TPH1 A218C polymorphism showed greater brain activity in the bilateral amygdala under the sad vs. the neutral condition compared with subjects homozygous for the C allele. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of amygdala activity in patients with MDD.
Lee
B-T
BT
Office of admissions, Seoul National University, Seoul, Korea.
Lee
H-Y
HY
Lee
B-C
BC
Pae
C-U
CU
Yoon
B-J
BJ
Ryu
S-G
SG
Choi
I-G
IG
Lee
M-S
MS
Ham
B-J
BJ
D000328:Adult; D000339:Affect / Q000502:physiology; D000679:Amygdala / Q000201:enzymology* / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics; D001931:Brain Mapping; D004252:DNA Mutational Analysis; D003865:Major Depressive Disorder / Q000201:enzymology* / Q000235:genetics* / Q000523:psychology; D005149:Facial Expression; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009483:Neuropsychological Tests; D010775:Photic Stimulation; D011110:Polymorphism, Genetic / Q000235:genetics*; D012701:Serotonin / Q000096:biosynthesis; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D012701:Serotonin; C497467:TPH1 protein, human; D014365:Tryptophan Hydroxylase