FKBP5 moderation of depressive symptoms in peer victimized, post-institutionalized children

Abstract

The purpose of this study was to examine whether FKBP5 rs1360780 moderates relations between different forms of life stress/adversity (early institutional rearing and peer victimization) and depressive symptoms in adolescents. As reported previously, PI youth were at risk for being victimized by peers. Here, victimization was associated with elevated depressive symptoms. While FKBP5 did not moderate the association between early life adversity and depressive symptoms for either sex, it moderated the association between current adversity and depressive symptoms for victimized girls carrying the minor allele. Consistent with a differential susceptibility model, girls with the minor allele exhibited more depressive symptoms at higher levels of victimization, but fewer depressive symptoms at lower levels of victimization. Interestingly, boys with the CC genotype had higher rates of depressive symptoms compared to girls with the CC genotype in the context of heightened victimization.

Gene–Stress–Epigenetic Regulation of FKBP5: Clinical and Translational Implications

“…(Binder et al, 2008;Klengel et al, 2013b) (Table 1). In a recent study in adolescents, FKBP5 genotype moderated the effects of current peer victimization but not early institutionalization before the age of two (VanZomeren-Dohm et al, 2015). These timedependent findings are in accordance with studies highlighting the role of stressor timing on neuroplasticity and risk for psychopathology (Gee and Casey, 2015).…”

Maternal regulation of the infant's hypothalamic‐pituitary‐adrenal axis stress response: Seymour ‘Gig’ Levine's legacy to neuroendocrinology

“…These adversities interact with the individual's genetic background, as has been shown with a polymorphism of the corticotrophin‐releasing hormone (CRH) receptor 1, which moderates the impact of childhood abuse on adulthood depression only in men, clearly indicating a sex‐specific interaction between genes and environment . Studies carried out by Megan Gunnar's group with Romanian orphans, exposed to all kinds of deprivation when in the orphanages and later adopted by American and Canadian families, show that the endocrine and psychological outcomes of this early‐life adversity depend on the length of institutionalisation and can be moderated by a polymorphism of the FKBP5 gene, a regulator of the glucocorticoid receptor (GR) affinity for cortisol . Another impressive finding concerning the impact of disrupted mother‐infant interaction comes from a study in which 6‐year‐old children raised by depressive mothers display more unstable emotional behaviours, are less empathic and exhibit lower plasma oxytocin levels than children raised by healthy mothers .…”

FKBP5 interacts with maltreatment in children with extreme, pervasive, and persistent aggression

“…There is a growing number of studies that report associations between common polymorphisms in FKBP5 and stress-related psychopathology, including post-traumatic stress (Sabbagh et al, 2014), other anxiety disorders (Minelli et al, 2013), and aggressive behaviour in adults with a history of childhood maltreatment (Bevilacqua et al, 2012). Studies in children are less numerous but associations with depressive symptoms (Van Zomeren-Dohm et al, 2015) and attention deficit and hyperactivity disorder (ADHD) (Isaksson et al, 2015) have been reported.…”