Increased brain activity to unpleasant stimuli in individuals with the 7R allele of the DRD4 gene

Jean-G Gehricke,James M Swanson,Sophie Duong,Jenny Nguyen,Timothy L Wigal,James Fallon,Cyrus Caburian,Lutfi Tugan Muftuler,Robert K Moyzis

doi:10.1016/j.pscychresns.2014.10.021

Abstract

The aim of the study was to examine functional brain activity in response to unpleasant images in individuals with the 7-repeat (7R) allele compared to individuals with the 4-repeat (4R) allele of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3). Based on the response ready hypothesis, individuals with the DRD4-4R/7R genotype were expected to show greater functional brain activity in response to unpleasant compared to neutral stimuli in specific regions of the frontal, temporal, parietal and limbic lobes, which form the networks involved in attentional, emotional, and preparatory responses. Functional Magnetic Resonance Imaging activity was studied in 26 young adults (13 with the DRD4-4R/7R genotype and 13 with the DRD4-4R/4R genotype). Participants were asked to look at and subjectively rate unpleasant and neutral images. Results showed increased brain activity in response to unpleasant images compared to neutral images in the right temporal lobe in participants with the DRD4-4R/7R genotype versus participants with the DRD4-4R/4R genotype. The increase in right temporal lobe activity in individuals with DRD4-4R/7R suggests greater involvement in processing negative emotional stimuli. Intriguingly, no differences were found between the two genotypes in the subjective ratings of the images. The findings corroborate the response ready hypothesis, which suggests that individuals with the 7R allele are more responsive to negative emotional stimuli compared to individuals with the 4R allele of the DRD4 gene.

Highlights

Dopamine is a key neurotransmitter, which regulates cognition, attention, emotional processing, motor activation, short-term memory, behavioral inhibition and reward (Wickens, 1990; Nieoullon, 2002; Dreber et al, 2009; Eisenberg et al, 2010b)
To provide additional information about brain activation patterns in response to unpleasant compared to neutral images for each genotype, Blood Oxygen Level Dependent (BOLD) contrasts from the first-level general linear model analysis (GLM) analyses were examined with a second-level random effects model analysis at p = 0.001 and a voxel threshold of 20
Individuals with the dopamine receptor D4 (DRD4)-4R/7R genotype, compared to the DRD4-4R/4R genotype, showed significant increased BOLD activity in the right temporal lobe in response to unpleasant versus neutral images

Summary

Introduction

Dopamine is a key neurotransmitter, which regulates cognition, attention, emotional processing, motor activation, short-term memory, behavioral inhibition and reward (Wickens, 1990; Nieoullon, 2002; Dreber et al, 2009; Eisenberg et al, 2010b). The 7-repeat (7R) of the DRD4 gene is the second most common allele with a global mean allele frequency of 20.6%, appearing with high frequency in the Americas (Chang et al, 1996). The 7R allele is estimated to have emerged 40,000 to 50,000 years ago, which is the same time that major human migration occurred (Wang et al, 2004). This genotype, including its homozygous and heterozygous variations, is found more frequently in populations who had to take great risks to travel long distances, such as early immigrants to the Americas (Chen et al, 1999; Eisenberg et al, 2010a). The association with risk taking was corroborated by research showing that individuals with the 7R allele of the DRD4 gene engage in more financial risk taking compared to those without this genotype (Dreber et al, 2009)

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