Human choline transporter gene variation is associated with corticolimbic reactivity and autonomic-cholinergic function

Biol Psychiatry. 2006 Nov 15;60(10):1155-62. doi: 10.1016/j.biopsych.2006.03.059. Epub 2006 Jul 28.


Background: Our previous work has shown genetic variation in the human choline transporter gene (CHT1) to be associated with depressive symptoms and autonomic cardiac (cholinergic) dysregulation. Here, functional magnetic resonance imaging (fMRI) was used to examine the relation between a single nucleotide polymorphism (SNP) in CHT1 on regional brain reactivity relevant to autonomic (cholinergic) function.

Methods: Thirty-two participants of European ancestry (18 men, 14 women; age: 33-54 years) completed an fMRI protocol using corticolimbic reactivity and prefrontal inhibitory control paradigms. Resting cholinergic function, as measured by heart rate variability (HRV), was quantified from electrocardiogram. Subjects were genotyped for a CHT1 G/T SNP.

Results: GG homozygotes had greater right (R) dorsal amygdala (p < .008), bilateral anterior cingulate (p < .009), and R caudate reactivity (p < .015) than T-allele carriers. Heart rate variability was related to R frontal cortex (Brodmann Areas 6, 9, and 46), R hippocampal formation, bilateral caudate, and bilateral anterior cingulate reactivity (p's < .007).

Conclusions: CHT1 variation is related to differences in a distributed corticolimbic circuitry mediating behavioral and physiologic arousal. These relations may contribute to a biological mechanism by which genetic variation in cholinergic neurotransmission affects cognition, mood, and autonomic cardiac function.

Publication types

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

MeSH terms

  • Adult
  • Autonomic Nervous System / physiology*
  • Brain Mapping
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / physiology*
  • Choice Behavior / physiology
  • Electrocardiography
  • Female
  • Genetic Variation*
  • Heart Rate / physiology
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Limbic System / blood supply
  • Limbic System / physiology*
  • Magnetic Resonance Imaging / methods
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Neural Pathways / blood supply
  • Neural Pathways / physiology*
  • Neuropsychological Tests
  • Oxygen / blood
  • Polymorphism, Single Nucleotide
  • White People


  • Membrane Transport Proteins
  • choline transporter
  • Oxygen