Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes

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.

Disrupting Reconsolidation of Fear Memory in Humans by a Noradrenergic β-Blocker

“…There is indeed an alternative method where extinction training is presented within the window of reconsolidation 49 . Several studies failed however to replicate these original findings by Schiller et al 29,50-52 but see 53,54 . In addition to these conflicting results, another potential limitation of the extinction within reactivation procedure would be that in clinical practice the fear response is generally not extinguished in a one-session exposure treatment.…”

A behavioural neuroscience perspective on the aetiology and treatment of anxiety disorders

“…Even though a one-session treatment of a low dose of propranolol is clearly nontoxic, an entirely behavioural procedure is always preferable over a pharmacological intervention, provided that similar effects can be obtained. There is indeed an alternative method where extinction training is presented within the window of reconsolidation in rodents (Clem & Huganir, 2010;Monfils, Cowansage, Klann, & LeDoux, 2009) and humans (Agren, Furmark, Eriksson, & Redrikson, 2012;Oyarzún et al, 2012;Schiller et al, 2010). Because memory retrieval techniques (i.e., renewal, reinstatement, spontaneous recovery) did not recover the conditioned fear responding, extinction within the reconsolidation window may also target the process of memory reconsolidation.…”

COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury

“…COMT Val158Met polymorphism ( rs4680 ) was genotyped utilizing the TaqMan ® SNP Genotyping Assay as described by the manufacturer (Applied Biosystems, Carlsbad, CA, Assay ID# C_25746809_50). For the purpose of evaluating a potential protective benefit of the Met 158 allele, Met 158 / Met 158 and Met 158 / Val 158 were combined as a single group as previously described for COMT [37–40] and other genetic polymorphisms in TBI [41–43]. Therefore, for data reporting and all figures, this group is referred to as Met 158 .…”