Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing

Biol Psychiatry. 2006 May 15;59(10):888-97. doi: 10.1016/j.biopsych.2005.11.005. Epub 2006 Jan 25.


Advances in molecular biology and neuroimaging have provided a unique opportunity to explore the relationships between genes, brain, and behavior. In this review, we will briefly outline the rationale for studying genetic effects on brain function with neuroimaging. We will then use studies of genetically driven variation in serotonin transporter function on corticolimbic structure and function to highlight the effectiveness of this strategy to delineate biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. In a series of studies, a relatively frequent regulatory variant of the human serotonin transporter gene (5-HTTLPR) has been demonstrated to bias the reactivity of the amygdala to salient environmental cues. Moreover, the 5-HTTLPR affects the development of a broader corticolimbic circuit and alters the functional integration of emotional information between the amygdala and medial prefrontal cortex. In turn, corticolimbic circuit function predicts individual differences in an experimental index of temperamental anxiety and, thus, might reflect a predictive biological marker of increased risk for mood disorders associated with the 5-HTTLPR.

Publication types

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

MeSH terms

  • Alleles
  • Amygdala / physiopathology*
  • Diagnostic Imaging*
  • Emotions / physiology*
  • Genetic Variation / genetics*
  • Humans
  • Mood Disorders / genetics*
  • Mood Disorders / physiopathology
  • Neural Pathways / physiopathology
  • Polymorphism, Genetic / genetics*
  • Prefrontal Cortex / physiopathology*
  • Serotonin / genetics*
  • Serotonin / physiology
  • Serotonin Plasma Membrane Transport Proteins / genetics
  • Synaptic Transmission / genetics*


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin