Amygdala-dependent fear conditioning in humans is modulated by the BDNFval66met polymorphism

Abstract

The brain-derived neurotrophic factor (BDNF) is critically involved in neuroplasticity, as well as the acquisition, consolidation, and retention of hippocampal- and amygdala-dependent learning. A common functional A-->G single nucleotide polymorphism (BDNFval66met) in the prodomain of the human BDNF gene is associated with abnormal intracellular trafficking and reduced activity-dependent BDNF release. We studied the effect of BDNFval66met in an aversive differential fear conditioning, and a delayed extinction paradigm in 57 healthy participants. Pictures of male faces were used as stimuli and fear learning was quantified by fear potentiated startle (FPS) and skin conductance responses (SCR). Aware BDNF met-carriers show a deficit in amygdala-dependent fear conditioning as indicated by an absence of FPS responses in the last acquisition block. This deficit was maintained in the first block of extinction. No genotype differences were found in conditioned SCR discrimination. These data provide evidence for the involvement of BDNF signaling in human amygdala-dependent learning. We suggest that the BDNF met-allele may have a protective effect for the development of affective pathologies that may be mediated via reduced synaptic plasticity induced by negative experience.

Figure 1

Fear potentiated startle reactions (T-scores) elicited during the CS+, CS−, and the intertrial interval (ITI) for the BDNFval66met genotype groups (val/val vs. met-carrier) during (A) late acquisition and (B) early extinction as well as skin conductance responses to the CS+ and CS− for the BDNFval66met genotype groups (val/val vs. met-carrier) during (C) late acquisition and (D) early extinction (^# p<0.10, * p < .05, ** p < .005, *** p < .001).

Figure 2

Fear potentiated startle reactions (T-scores) elicited during the CS+, CS−, and the intertrial interval (ITI) for (A) BDNF val/val and (B) met-carrier during the two acquisition blocks and the four extinction blocks as well as skin conductance responses to the CS+ and CS− for (C) BDNF val/val and (D) met-carrier during the two acquisition blocks and the four extinction blocks.