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1.
  • Agren, T, et al. (författare)
  • Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes.
  • 2012
  • Ingår i: Translational psychiatry. - 2158-3188. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Fear memory persistence, central for the development and maintenance of anxiety disorders, is partially genetically controlled. Recently, consolidation and reconsolidation processes have been reported to affect fear memory stability and integrity. This study explored the impact of reconsolidation processes and genetic make-up on fear reacquisition by manipulating reconsolidation, using extinction performed outside or inside a reconsolidation interval. Reacquisition measured by skin conductance responses was stronger in individuals that extinguished outside (6 h) than inside (10 min) the reconsolidation interval. However, the effect was predominantly present in val/val homozygotes of the functional val158met polymorphism of the catechol O-methyltransferase (COMT) enzyme and in short-allele carriers of the serotonin-transporter length 5-HTTLPR polymorphism. These results demonstrate that reconsolidation of human fear memory is influenced by dopamine and serotonin-related genes.
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  • Bazov, Igor, 1973-, et al. (författare)
  • Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics
  • 2018
  • Ingår i: Translational Psychiatry. - Nature Publishing Group. - 2158-3188 .- 2158-3188. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive-like drug and alcohol self-administration in animal models. In human brain, the DYN/KOR system may undergo adaptive changes, which along with neuronal loss, may contribute to alcohol-associated cognitive deficit. We addressed this hypothesis by comparing the expression levels and co-expression (transcriptionally coordinated) patterns of PDYN and KOR (OPRK1) genes in dorsolateral prefrontal cortex (dlPFC) between human alcoholics and controls. Postmortem brain specimens of 53 alcoholics and 55 controls were analyzed. PDYN was found to be downregulated in dlPFC of alcoholics, while OPRK1 transcription was not altered. PDYN downregulation was confined to subgroup of subjects carrying C, a high-risk allele of PDYN promoter SNP rs1997794 associated with alcoholism. Changes in PDYN expression did not depend on the decline in neuronal proportion in alcoholics, and thereby may be attributed to transcriptional adaptations in alcoholic brain. Absolute expression levels of PDYN were lower compared to those of OPRK1, suggesting that PDYN expression is a limiting factor in the DYN/KOR signaling, and that the PDYN downregulation diminishes efficacy of DYN/KOR signaling in dlPFC of human alcoholics. The overall outcome of the DYN/KOR downregulation may be disinhibition of neurotransmission, which when overactivated could contribute to formation of alcohol-related behavior.</p>
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9.
  • Bergman, O, et al. (författare)
  • Association between amygdala reactivity and a dopamine transporter gene polymorphism
  • 2014
  • Ingår i: Translational Psychiatry. - Nature Publishing Group. - 2158-3188 .- 2158-3188. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>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.</p>
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10.
  • Bergman, Olle, 1978-, et al. (författare)
  • Association between amygdala reactivity and a dopamine transporter gene polymorphism.
  • 2014
  • Ingår i: Translational psychiatry. - 2158-3188. ; 4
  • Tidskriftsartikel (refereegranskat)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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