The Interaction of Child Abuse and rs1360780 of the FKBP5 Gene is Associated with Amygdala Resting-State Functional Connectivity in Young Adults

Abstract

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 risk for psychopathology.

Mapping gene by early life stress interactions on child subcortical brain structures: A genome‐wide prospective study

“…Taken together, evidence to date points to a key role of both genetic and environmental factors in subcortical brain development. However, few studies have examined gene‐environment interactions on the brain (Gao et al., 2019) and, of these, most have looked at candidate genes, primarily focussing on monoamine neurotransmitter (Meer et al., 2015; Reed et al., 2018) and neuroendocrine‐related (Malhi et al., 2020; Wesarg et al., 2021) pathways. Other studies have employed polygenic scores (PGS) based on GWAS of psychiatric disorders and subsequently examined interactive effects with specific environmental stressors on brain structure (Acosta et al., 2020; Bolhuis et al., 2019; French et al., 2015).…”