The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning

•BDNF Val66Met genotype is associated with PTSD risk and poor fear extinction.•Poor fear extinction is a key mechanism involved in PTSD.•The BDNF Val66Met genotype moderated between PTSD severity and fear extinction.•Those with the met allele displayed poorer fear extinction and greater PTSD severit...

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Published in:	Psychoneuroendocrinology 2018-05, Vol.91, p.142-148
Main Authors:	Felmingham, Kim L., Zuj, Daniel V., Hsu, Ken Chia Ming, Nicholson, Emma, Palmer, Matthew A., Stuart, Kimberley, Vickers, James C., Malhi, Gin S., Bryant, Richard A.
Format:	Article
Language:	eng
Subjects:	Adult Alleles BDNF Brain derived neurotrophic factor Brain-Derived Neurotrophic Factor - genetics Brain-Derived Neurotrophic Factor - metabolism Extinction, Psychological - physiology Fear - psychology Fear extinction Female Humans Implosive Therapy - methods Learning - physiology Male Middle Aged Polymorphism, Single Nucleotide - genetics Posttraumatic Stress Disorder PTSD Stress Disorders, Post-Traumatic - genetics Stress Disorders, Post-Traumatic - metabolism
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Summary:	•BDNF Val66Met genotype is associated with PTSD risk and poor fear extinction.•Poor fear extinction is a key mechanism involved in PTSD.•The BDNF Val66Met genotype moderated between PTSD severity and fear extinction.•Those with the met allele displayed poorer fear extinction and greater PTSD severity.•Those with the val–val allele displayed no relationship between extinction and PTSD. The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val–Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val–Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val–Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy.
ISSN:	0306-4530 1873-3360