Serotonin transporter genetic variation and the response of the human amygdala.
A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5- hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Ahmad R
AR
Hariri
Venkata S
VS
Mattay
Alessandro
A
Tessitore
Bhaskar
B
Kolachana
Francesco
F
Fera
David
D
Goldman
Michael F
MF
Egan
Daniel R
DR
Weinberger
D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D005149:Facial Expression; D005239:Fear; D005260:Female; D007839:Functional Laterality; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010551:Personality; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D012727:Sex Characteristics
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin