Genetic variation in serotonin transporter alters resting brain function in healthy individuals

Biol Psychiatry. 2007 Sep 15;62(6):600-6. doi: 10.1016/j.biopsych.2006.11.028. Epub 2007 May 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amygdala / physiopathology
  • Brain / blood supply
  • Brain / physiopathology*
  • Brain Mapping
  • Depressive Disorder / epidemiology
  • Depressive Disorder / genetics
  • Depressive Disorder / physiopathology
  • Frontal Lobe / physiopathology
  • Genetic Predisposition to Disease
  • Genetic Variation / genetics*
  • Genetic Variation / physiology
  • Genotype
  • Humans
  • Magnetic Resonance Imaging / statistics & numerical data
  • Polymorphism, Genetic
  • Prefrontal Cortex / physiopathology
  • Regional Blood Flow / genetics
  • Regional Blood Flow / physiology
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / physiology


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins