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 the risk for psychopathology.
Highlights
Several lines of research suggest that genetic predisposition as well as child abuse are important risk factors for psychopathology (e.g., McCrory, De Brito, & Viding, 2012), and that the interaction of these factors can account for variance above main effects of genotype and environment (Belsky & Pluess, 2009; Rutter, Moffitt, & Caspi, 2006)
Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting-state functional connectivity between the amygdala and other areas of the salience network
In the absence of main effects of genotype and abuse, a significant interaction effect was observed for resting-state functional connectivity (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
Summary
Several lines of research suggest that genetic predisposition as well as child abuse are important risk factors for psychopathology (e.g., McCrory, De Brito, & Viding, 2012), and that the interaction of these factors can account for variance above main effects of genotype and environment (Belsky & Pluess, 2009; Rutter, Moffitt, & Caspi, 2006). In line with the suggestion that a reduced GR sensitivity would lead to a prolonged stress response, higher cortisol levels during recovery after stress have been observed in healthy TT carriers (Ising et al, 2008), paralleling the observation in individuals with MDD (Burke et al, 2005) Given these findings, dysregulation of the HPA axis, associated with both exposure to child abuse and FKBP5 risk genotype, may be exaggerated by their interaction, possibly due to epigenetic mechanisms such as T-allele specific stress-related demethylation at glucocorticoid response elements (Matosin, Halldorsdottir, & Binder, 2018). During sensitive developmental periods, as in childhood or adolescence, heightened levels of circulating cortisol can differentially modify the maturation and function of brain regions involved in regulation and adaptation in response to stress including the prefrontal cortex, amygdala, and hippocampus (Danese & McEwen, 2012; Lupien et al, 2009; McCrory et al, 2010). In line with the finding of Teicher et al (2016), we hypothesized that individuals with a history of child abuse carrying the TT allele of rs1360780 would show altered coupling between seed regions of the amygdala, the CMA, and regions of the SN, including the insula and the ACC, compared with CT/CC allele carriers with and without a history of child abuse
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