BDNF val66met affects hippocampal volume and emotion-related hippocampal memory activity

The val⁶⁶met polymorphism on the BDNF gene has been reportedto explain individual differences in hippocampal volume and memory-relatedactivity. These findings, however, have not been replicated consistently and nostudies to date controlled for the potentially confounding impact of early lifestress, such as childhood abuse, and psychiatric status. Using structural andfunctional MRI, we therefore investigated in 126 depressed and/or anxiouspatients and 31 healthy control subjects the effects of val⁶⁶met onhippocampal volume and encoding activity of neutral, positive and negativewords, while taking into account childhood abuse and psychiatric status. Ourresults show slightly lower hippocampal volumes in carriers of a met allele(n=54) relative to val/val homozygotes(n=103) (P=0.02, effect size (Cohen''sd)=0.37), which appeared to be independent of childhoodabuse and psychiatric status. For hippocampal encoding activity, we found aval⁶⁶met–word valence interaction (P=0.02)such that carriers of a met allele showed increased levels of activation inresponse to negative words relative to activation in the neutral word conditionand relative to val/val homozygotes. This, however, was only evident in theabsence of childhood abuse, as abused val/val homozygotes showed hippocampalencoding activity for negative words that was comparable to that of carriers ofa met allele. Neither psychiatric status nor memory accuracy did account forthese associations. In conclusion, BDNF val⁶⁶met has a significantimpact on hippocampal volume independently of childhood abuse and psychiatricstatus. Furthermore, early adverse experiences such as childhood abuse accountfor individual differences in hippocampal encoding activity of negative stimulibut this effect manifests differently as a function of val⁶⁶met.