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Association between amygdala reactivity and a dopamine transporter gene polymorphism.

Bergman O, Åhs F, Furmark T, Appel L, Linnman C, Faria V, Bani M, Pich EM, Bettica P, Henningsson S, Manuck SB, Ferrell RE, Nikolova YS, Hariri AR, Fredrikson M, Westberg L, Eriksson E - Transl Psychiatry (2014)

Bottom Line: The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA.In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes.The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

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Differences (P<0.05) in left amygdala reactivity between SLC6A3 dichotomized genotype subgroups. (a) The amygdala regions of interest used to extract data in the Swedish sample (PET) are shown overlaid on an anatomical template. (b) Scatter plot showing left amygdala reactivity in the Swedish sample. (c) The amygdala regions of interest used to extract data in the US sample (fMRI). (d) Scatter plot showing left amygdala reactivity in the US sample. 9 carriers, carriers of one or two 9-repeats; 10/10, carriers of two 10-repeats; PET, positron emission tomography; SLC6A3, dopamine transporter gene.
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fig1: Differences (P<0.05) in left amygdala reactivity between SLC6A3 dichotomized genotype subgroups. (a) The amygdala regions of interest used to extract data in the Swedish sample (PET) are shown overlaid on an anatomical template. (b) Scatter plot showing left amygdala reactivity in the Swedish sample. (c) The amygdala regions of interest used to extract data in the US sample (fMRI). (d) Scatter plot showing left amygdala reactivity in the US sample. 9 carriers, carriers of one or two 9-repeats; 10/10, carriers of two 10-repeats; PET, positron emission tomography; SLC6A3, dopamine transporter gene.

Mentions: In neither the PET population nor the fMRI population did the distribution of observed SLC6A3 genotypes (Table 1) deviate from Hardy–Weinberg equilibrium. Left amygdala reactivity, that is, the mean rCBF during the processing of angry faces, as compared with that during the processing of neutral faces, was positively associated with the presence of one or two 9-repeats in the Swedish sample (Table 2, Figure 1), with no indication of an influence of diagnostic category (SAD: 9 repeats mean±s.d.=0.031±0.05, 10 repeats mean±s.d.=0.004±0.02; healthy volunteer: 9 repeats mean±s.d.=0.024±0.06, 10 repeats mean±s.d.=−0.003±.03) on this association. This observation is in line with the results of the US sample of healthy volunteers, in which amygdala reactivity, that is, regional BOLD parameter estimates from the comparison of threatening faces and geometric shapes, was also positively associated with carrying one or two 9-repeats (n=43) as compared with two 10-repeats (n=42) (Table 2, Figure 1, Supplementary Figure). Right amygdala reactivity did not differ between genotypes in either of the two samples (Table 2).


Association between amygdala reactivity and a dopamine transporter gene polymorphism.

Bergman O, Åhs F, Furmark T, Appel L, Linnman C, Faria V, Bani M, Pich EM, Bettica P, Henningsson S, Manuck SB, Ferrell RE, Nikolova YS, Hariri AR, Fredrikson M, Westberg L, Eriksson E - Transl Psychiatry (2014)

Differences (P<0.05) in left amygdala reactivity between SLC6A3 dichotomized genotype subgroups. (a) The amygdala regions of interest used to extract data in the Swedish sample (PET) are shown overlaid on an anatomical template. (b) Scatter plot showing left amygdala reactivity in the Swedish sample. (c) The amygdala regions of interest used to extract data in the US sample (fMRI). (d) Scatter plot showing left amygdala reactivity in the US sample. 9 carriers, carriers of one or two 9-repeats; 10/10, carriers of two 10-repeats; PET, positron emission tomography; SLC6A3, dopamine transporter gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150236&req=5

fig1: Differences (P<0.05) in left amygdala reactivity between SLC6A3 dichotomized genotype subgroups. (a) The amygdala regions of interest used to extract data in the Swedish sample (PET) are shown overlaid on an anatomical template. (b) Scatter plot showing left amygdala reactivity in the Swedish sample. (c) The amygdala regions of interest used to extract data in the US sample (fMRI). (d) Scatter plot showing left amygdala reactivity in the US sample. 9 carriers, carriers of one or two 9-repeats; 10/10, carriers of two 10-repeats; PET, positron emission tomography; SLC6A3, dopamine transporter gene.
Mentions: In neither the PET population nor the fMRI population did the distribution of observed SLC6A3 genotypes (Table 1) deviate from Hardy–Weinberg equilibrium. Left amygdala reactivity, that is, the mean rCBF during the processing of angry faces, as compared with that during the processing of neutral faces, was positively associated with the presence of one or two 9-repeats in the Swedish sample (Table 2, Figure 1), with no indication of an influence of diagnostic category (SAD: 9 repeats mean±s.d.=0.031±0.05, 10 repeats mean±s.d.=0.004±0.02; healthy volunteer: 9 repeats mean±s.d.=0.024±0.06, 10 repeats mean±s.d.=−0.003±.03) on this association. This observation is in line with the results of the US sample of healthy volunteers, in which amygdala reactivity, that is, regional BOLD parameter estimates from the comparison of threatening faces and geometric shapes, was also positively associated with carrying one or two 9-repeats (n=43) as compared with two 10-repeats (n=42) (Table 2, Figure 1, Supplementary Figure). Right amygdala reactivity did not differ between genotypes in either of the two samples (Table 2).

Bottom Line: The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA.In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes.The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.

Show MeSH
Related in: MedlinePlus