The interaction of child abuse and rs1360780 of the FKBP5 gene is associated with amygdala resting-state functional connectivity in young adults

• Main Authors: Artiges, E. (Author), Banaschewski, T. (Author), Barker, G.J (Author), Bokde, A.L.W (Author), Brühl, R. (Author), Daedelow, L.S (Author), Desrivières, S. (Author), Flor, H. (Author), Fröhner, J.H (Author), Garavan, H. (Author), Grigis, A. (Author), Heinz, A. (Author), Hohmann, S. (Author), IMAGEN Consortium (Author), Lett, T.A (Author), Martinot, J.-L (Author), Nees, F. (Author), Oei, N.Y.L (Author), Orfanos, D.P (Author), Poustka, L. (Author), Quinlan, E.B (Author), Schumann, G. (Author), Smolka, M.N (Author), Veer, I.M (Author), Walter, H. (Author), Wesarg, C. (Author), Whelan, R. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: adolescent; Adolescent; adult; Adult; Adult Survivors of Child Abuse; Adverse Childhood Experiences; amygdala; Amygdala; Article; brain region; child abuse; child abuse survivor; clinical trial; connectome; Connectome; diagnostic imaging; early life stress; emotional network; female; Female; fk 506 binding protein; FKBP5; fkbp5 protein; functional connectivity; functional magnetic resonance imaging; gene–environment interaction; Gene-Environment Interaction; genetics; genotype environment interaction; heterozygote; human; Humans; Magnetic Resonance Imaging; major clinical study; male; Male; mental disease; multicenter study; nuclear magnetic resonance imaging; phenotype; physiology; Polymorphism, Single Nucleotide; posterior insula; protein; resting-state functional connectivity; rs1360780; salience network; sensation; single nucleotide polymorphism; tacrolimus binding protein 5; Tacrolimus Binding Proteins; unclassified drug; young adult; Young Adult
• Online Access: View Fulltext in Publisher
• ISBN: 10659471 (ISSN)
• DOI: 10.1002/hbm.25433

Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early-life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion-processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p <.025, FWE-corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. © 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.