Background
Dopamine modulation of neuronal activity in prefrontal cortex maps to an inverted
U-curve. Dopamine is also an important factor in regulation of hippocampal mediated
memory processing. Here, we investigated the effect of genetic variation of dopamine
inactivation via catechol-O-methyltransferase (COMT) and the dopamine transporter
(DAT) on hippocampal activity in healthy humans during different memory conditions.
Methods
Using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging
(fMRI) in 82 subjects matched for a series of demographic and genetic variables, we
studied the effect of the COMT valine (Val)158methionine (Met) and the DAT 3′ variable number tandem repeat (VNTR) polymorphisms
on function of the hippocampus during encoding of recognition memory and during working
memory.
Results
Our results consistently demonstrated a double dissociation so that DAT 9-repeat carrier
alleles modulated activity in the hippocampus in the exact opposite direction of DAT
10/10-repeat alleles based on COMT Val158Met genotype during different memory conditions. Similar results were evident in ventrolateral
and dorsolateral prefrontal cortex.
Conclusions
These findings suggest that genetically determined dopamine signaling during memory
processing maps to a nonlinear relationship also in the hippocampus. Our data also
demonstrate in human brain epistasis of two genes implicated in dopamine signaling
on brain activity during different memory conditions.
Key Words
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Article info
Publication history
Published online: March 31, 2008
Accepted:
February 6,
2008
Received in revised form:
December 14,
2007
Received:
August 24,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
