A review on experimental and clinical genetic associations studies on fear conditioning, extinction and cognitive-behavioral treatment

Abstract

Fear conditioning and extinction represent basic forms of associative learning with considerable clinical relevance and have been implicated in the pathogenesis of anxiety disorders. There is considerable inter-individual variation in the ability to acquire and extinguish conditioned fear reactions and the study of genetic variants has recently become a focus of research. In this review, we give an overview of the existing genetic association studies on human fear conditioning and extinction in healthy individuals and of related studies on cognitive-behavioral treatment (CBT) and exposure, as well as pathology development after trauma. Variation in the serotonin transporter (5HTT) and the catechol-o-methyltransferase (COMT) genes has consistently been associated with effects in pre-clinical and clinical studies. Interesting new findings, which however require further replication, have been reported for genetic variation in the dopamine transporter (DAT1) and the pituitary adenylate cyclase 1 receptor (ADCYAP1R1) genes, whereas the current picture is inconsistent for variation in the brain-derived neurotrophic factor (BDNF) gene. We end with a discussion of the findings and their limitations, as well as future directions that we hope will aid the field to develop further.

Neuronal encoding of the switch from specific to generalized fear

“…This occludes any further skewing toward greater generalization both at the behavioral and neuronal levels. This is important in light of accumulating evidence on the relevance of individual differences in stress disorders and generalization 38 . We found inherent differences between these two groups of rats.…”

Identifying mechanisms that underlie links between COMT genotype and aggression in male adolescents with ADHD

“…They suggest that Val carriers versus Met/Met genotype show reduced startle in response to fear stimuli (Montag et al., 2008) and lower fear memory consolidation (e.g.Lonsdorf & Kalisch, 2011). Our findings were not explained by lower levels of anxiety symptoms (as assessed by parent or adolescent rated SDQ) in the Met/Met group (see Table 1).…”

The Role of Stress and Fear in the Development of Mental Disorders

“…In terms of using fear for screening, the genetic heritability of conditioning and extinction is 35-45% [53]. There is some evidence that genetic variation in the serotonin transporter gene affects conditionability, the catechol-O-methyltransferase gene affects fear memory consolidation and the brain-derived neurotrophic factor (BDNF) val66met genotype has been found to have various effects on conditioning and extinction processes [54]. Thus the capacity for fear conditioning and/or extinction might be an inheritable risk factor for the development of PTSD and might be used as a way to identify people at risk before being exposed to trauma.…”