Human choline transporter gene variation is associated with corticolimbic reactivity and autonomic-cholinergic function.
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.
Neumann
Serina A
SA
Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, 825 Fairfax Avenue, Norfolk, VA 23501. Neumans@evms.edu
Brown
Sarah M
SM
Ferrell
Robert E
RE
Flory
Janine D
JD
Manuck
Stephen B
SB
Hariri
Ahmad R
AR
D000328:Adult; D001341:Autonomic Nervous System / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000098:blood supply / Q000502:physiology*; D002755:Choice Behavior / Q000502:physiology; D004562:Electrocardiography; D005260:Female; D014644:Genetic Variation; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008032:Limbic System / Q000098:blood supply / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D044465:White People
D026901:Membrane Transport Proteins; C065637:choline transporter; D010100:Oxygen