Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder

• Published in: Genes, brain and behavior Vol. 8; no. 5; pp. 512 - 518
• Main Authors: Lee, B.‐T., Lee, H.‐Y., Lee, B.‐C., Pae, C.‐U., Yoon, B.‐J., Ryu, S.‐G., Choi, I.‐G., Lee, M.‐S., Ham, B.‐J.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2009
• Subjects: Adult; Affect - physiology; Amygdala - enzymology; Amygdala - physiopathology; anger; Brain Chemistry - genetics; Brain Mapping; Depressive Disorder, Major - enzymology; Depressive Disorder, Major - genetics; Depressive Disorder, Major - psychology; DNA Mutational Analysis; Facial Expression; Female; Functional Laterality - genetics; Functional magnetic resonance imaging; Gene Frequency - genetics; Genetic Predisposition to Disease - genetics; Genetic Testing; Genotype; Humans; Magnetic Resonance Imaging; major depressive disorder; Middle Aged; Neuropsychological Tests; Photic Stimulation; polymorphism; Polymorphism, Genetic - genetics; sadness; Serotonin - biosynthesis; tryptophan hydroxylase; Tryptophan Hydroxylase - genetics
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/j.1601-183X.2009.00500.x

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.