Genetic variation in serotonin transporter alters resting brain function in healthy individuals.
BACKGROUND
Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals.


METHODS
Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores.


RESULTS
Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood.


CONCLUSIONS
The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.
Rao
Hengyi
H
Center for Functional Neuroimaging, Department of Neurology and Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA. hengyi@mail.med.upenn.edu
Gillihan
Seth J
SJ
Wang
Jiongjiong
J
Korczykowski
Marc
M
Sankoorikal
Geena Mary V
GM
Kaercher
Kristin A
KA
Brodkin
Edward S
ES
Detre
John A
JA
Farah
Martha J
MJ
D000679:Amygdala / Q000503:physiopathology; D001921:Brain / Q000098:blood supply / Q000503:physiopathology*; D001931:Brain Mapping; D003866:Depressive Disorder / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D005625:Frontal Lobe / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics* / Q000502:physiology; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000503:physiopathology; D012039:Regional Blood Flow / Q000235:genetics / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins