The authors T. O. and A. H. K. are supported by an Australian Postgraduate Award (APA) and a National Health and Medical Research Council (NHMRC) Career Development Award Fellowship (571101), respectively. This research was further supported by an Australian Research Council (ARC) Discovery Project (DP0987332) and an NHMRC Project Grant (464863) awarded to A. H. K. DNA was extracted by Genetic Repositories Australia, which is supported by an NHMRC Grant (401184). K. G. is supported by a scholarship from an ARC laureate. G. M. has received research support from AstraZeneca, Eli Lilly, Organon, Pfizer, Servier, and Wyeth.
The functional epistasis of 5-HTTLPR and BDNF Val66Met on emotion processing: a preliminary study
Version of Record online: 3 OCT 2012
© 2012 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Brain and Behavior
Volume 2, Issue 6, pages 778–788, November 2012
How to Cite
Brain and Behavior 2012; 2(6): 778–788
- Issue online: 9 NOV 2012
- Version of Record online: 3 OCT 2012
- Manuscript Accepted: 12 SEP 2012
- Manuscript Received: 4 SEP 2012
- Australian Postgraduate Award (APA)
- National Health and Medical Research Council (NHMRC). Grant Number: 571101
- Australian Research Council (ARC). Grant Numbers: DP0987332, 464863, 401184
- Eli Lilly
- BDNF Val66Met;
- emotion processing;
- fMRI ;
- healthy subjects
An epistatic interaction of 5-HTTLPR and BDNF Val66Met polymorphisms has been implicated in the structure of rostral anterior cingulate cortex (rACC) and amygdala (AMY): key regions associated with emotion processing. However, a functional epistasis of 5-HTTLPR and BDNF Val66Met on overt emotion processing has yet to be determined. Twenty-eight healthy, Caucasian female participants provided saliva samples for genotyping and underwent functional magnetic resonance imaging (fMRI) during which an emotion processing protocol were presented. Confirming the validity of this protocol, we observed blood oxygen level–dependent (BOLD) activity consistent with fMRI meta-analyses on emotion processing. Region-of-interest analysis of the rACC and AMY revealed main effects of 5-HTTLPR and BDNF Val66Met, and an interaction of 5-HTTLPR and BDNF Val66Met. The effect of the BDNF Met66 allele was dependent on 5-HTTLPR alleles, such that participants with S and Met alleles had the greatest rACC and AMY activation during the presentation of emotional images relative to other genetic groupings. Increased activity in these regions was interpreted as increased reactivity to emotional stimuli, suggesting that those with S and Met alleles are more reactive to emotional stimuli relative to other groups. Although limited by a small sample, this study contributes novel and preliminary findings relating to a functional epistasis of the 5-HTTLPR and BDNF Val66Met genes in emotion processing and provides guidance on appropriate methods to determine genetic epistasis in fMRI.