https://repub.eur.nl/pub/120844/Repub_120844_O-A.pdf

Don't fear 'fear conditioning': Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wps.20656

Post-traumatic stress disorder: a state-of-the-art review of evidence and challenges

Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders.

Stress and Fear Extinction.

More than just noise: Inter-individual differences in fear acquisition, extinction and return of fear in humans - Biological, experiential, temperamental factors, and methodological pitfalls.

Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.

/pdf/serotonin-transporter-polyadenylation-polymorphism-modulates-5g6cuy5c75.pdf

Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory

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Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory