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Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
Sektionen för farmakologi, Göteborgs universitet.
Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
2012 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 2, e76Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Macmillan Publishers Ltd., 2012. Vol. 2, e76
Keyword [en]
dopamine, fear conditioning, genes, memory reconsolidation, polymorphism, serotonin
National Category
Psychology
Identifiers
URN: urn:nbn:se:uu:diva-180177DOI: 10.1038/tp.2012.5ISI: 000315989800001PubMedID: 22832813OAI: oai:DiVA.org:uu-180177DiVA: diva2:548747
Funder
Swedish Research CouncilForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2012-08-31 Created: 2012-08-31 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Erasing Fear: Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity
Open this publication in new window or tab >>Erasing Fear: Effect of Disrupting Fear Memory Reconsolidation on Central and Peripheral Nervous System Activity
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fear memories, here defined as learned associations between a stimulus and a physiological fear reaction, are formed through fear conditioning. In animals, fear memories, present in the lateral amygdala, undergo reconsolidation after recall. Moreover, this reconsolidation process can be disrupted both pharmacologically and behaviourally, resulting in a reduced fear response to the stimulus. This thesis examines the attenuation of fear memories by disrupting reconsolidation in humans, using measures of both the central and peripheral nervous system activity. Serotonergic and dopaminergic genes have previously been tied to both fear conditioning and anxiety disorders, where fear conditioning mechanisms are important. In order to evaluate the possible role of fear memory reconsolidation mechanims in the effect on fear and anxiety by these genes, this thesis also compare the reconsolidation disruption effect between different serotonergic and dopaminergic genotypes.

Study I examined the attentuation of fear memories by disrupting reconsolidation in humans using reacquisition as a measure of the return of fear. Moreover, study I investigated the impact of differences in serotonergic and dopaminergic alleles on this process.

Study II examined the attentuation of fear memories by disrupting reconsolidation in humans using reinstatement as a measure of the return of fear. Study II also investigated the impact of differences in serotonergic and dopaminergic alleles on the process of fear memory reconsolidation.

Study III used psychophysiology and fMRI to localize the functional neural activity mediating the fear memory reconsolidation disruption effect.

In summary, this thesis provides evidence that fear memories are attenuated by reconsolidation disruption in humans and that serotonergic and dopaminergic alleles influence this process. Moreover, this thesis support that human fear memory reconsolidation is amygdala-dependent, suggesting an evolutionary shared memory mechanism.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2012. 62 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 81
Keyword
Memory reconsolidation; fear conditioning; serotonin; dopamine; polymorphism; gene; exposure therapy; fMRI; amygdala
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-180202 (URN)978-91-554-8455-2 (ISBN)
Public defence
2012-10-12, Universitetshuset, Sal IX, Biskopsgatan 3, Uppsala, 13:15 (Swedish)
Supervisors
Funder
Swedish Research Council
Available from: 2012-09-21 Created: 2012-08-31 Last updated: 2013-01-23Bibliographically approved

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Ågren, ThomasFurmark, TomasFredrikson, Mats

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