학술논문
The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing
Document Type
Report
Author
Redlich, Ronny; Schneider, Ilona; Kerkenberg, Nicole; Opel, Nils; Bauhaus, Jonas; Enneking, Verena; Repple, Jonathan; Leehr, Elisabeth J.; Grotegerd, Dominik; Kähler, Claas; Förster, Katharina; Dohm, Katharina; Meinert, Susanne; Hahn, Tim; Kugel, Harald; Schwarte, Kathrin; Schettler, Christiane; Domschke, Katharina; Arolt, Volker; Heindel, Walter; Baune, Bernhard T.; Zhang, Weiqi; Hohoff, Christa; Dannlowski, Udo
Source
Human Brain Mapping. October 15, 2019, Vol. 41 Issue 3, p594, 11 p.
Subject
Language
English
ISSN
1065-9471
Abstract
INTRODUCTION The brain derived neurotrophic factor (BDNF) has been shown to play a crucial role in neural development, function and plasticity of the amygdala, mediating anxiety‐like behaviors (Sagarkar et al., [...]
: Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val[sup.66]Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val[sup.66]Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = −26, t[sub.(166)] = 3.00, TFCE = 42.39, p[sub.(FWE)] =.045), whereby the BDNF‐Val[sup.66]Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = −.19, p =.015) and amygdala reactivity (r = −.17, p =.028), while harm avoidance showed a trend for a positive association with BDNF methylation (r =.14, p =.066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.
: Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val[sup.66]Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val[sup.66]Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = −26, t[sub.(166)] = 3.00, TFCE = 42.39, p[sub.(FWE)] =.045), whereby the BDNF‐Val[sup.66]Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = −.19, p =.015) and amygdala reactivity (r = −.17, p =.028), while harm avoidance showed a trend for a positive association with BDNF methylation (r =.14, p =.066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.