Short CommunicationFKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents
Introduction
Due to the rising prevalence of depression and anxiety (Mathers and Loncar, 2006), investigating factors associated with increased risk of these disorders in premorbid adolescent populations is important. Adolescence is a high-risk period for the onset of psychiatric disorders due to the accelerated psychological, biological and endocrine development occuring during this time in the lifespan, which interacts with the intensified stress and emotional responsiveness to the social environment (Paus et al., 2008). Accordingly, an increased understanding of risk and resilience factors during this sensitive developmental stage may be crucial in developing effective preventative interventions.
Maladaptive emotion regulation strategies, such as rumination and catastrophizing, have been identified as transdiagnostic risk factors for psychopathology (Gellatly and Beck, 2016, Ottaviani et al., 2016). Rumination refers to the tendency to perseverate on negative cognitions and the potential causes and consequences of distress (Nolen-Hoeksema, 2000, Ottaviani et al., 2016). Catastrophizing, on the other hand, is the tendency to overestimate negative consequences associated with an event (Gellatly and Beck, 2016). Both rumination and catastrophizing have been associated with the onset, maintenance, and recurrence of mood and anxiety disorders (Gellatly and Beck, 2016, Ottaviani et al., 2016).
Overall, risk for psychiatric disorders is associated with environmental and genetic factors, as well as their interactions (Halldorsdottir and Binder, 2017). One of the most consistent risk factors for psychopathology in adulthood is exposure to childhood trauma, and various genetic polymorphisms have been described to moderate this relationship. Among these genetic markers are variants within the gene encoding the FK506-binding protein 51 FKBP5, which plays an important role in the hypothalamic-pituitary-adrenal (HPA) axis through its regulatory role of glucocorticoid receptor sensitivity (Binder, 2009). Gene-by-environment interaction (G × E) studies have found that minor allele carriers of a haplotype derived of 4 variants (rs9296158, rs3800373, rs1360780, and rs9470080), referred to as CATT carriers, are at greater risk of developing a range of psychiatric disorders in adulthood following childhood trauma relative to major allele carriers (Zannas et al., 2016). Only few studies have, however, examined the moderating role of FKBP5 on transdiagnostic psychological risk factors for psychopathology in youth, especially adolescents (Comasco et al., 2015, Isaksson et al., 2016). Toward bridging this gap, the current study investigated the combined predictive effect of this FKBP5 haplotype and exposure to childhood trauma on the maladaptive emotion regulation strategies described above. Given that this FKBP5 haplotype has shown moderating effects of childhood adversities across psychiatric disorders, we hypothesized that these transdiagnostic emotion regulation processes would also be affected in that CATT haplotype carriers exposed to higher levels of childhood trauma would present with the higher level of rumination and catastrophizing compared to non-carriers.
Section snippets
Participants
Participants were drawn from a larger study comprising 1459 students between the ages 12–17 and their parents recruited from 31 schools in Portugal in 2011–2012 and 2013–2014. A total of 1345 genotyped adolescents between the ages 12–17 (Mage = 13.95, 64.2% female; 100% European Caucasians of Portuguese nationality) completed the measures required for the present study (see Table 1 for sample characteristics). All subjects’ parents completed consent forms and students completed assent forms prior
Results
Demographic and clinical characteristics of the sample are presented in Table 1. No significant differences were noted based on FKBP5 genotype. Higher levels of rumination and catastrophizing were however observed among participants with lower socioeconomic status (SES) status (p < 0.001). Additionally, females endorsed higher levels of rumination and catastrophizing than males (p < 0.001). SES and biological sex and their interaction with the independent variables (i.e., exposure to childhood
Discussion
We found that FKBP5 haplotype interacted with exposure to childhood trauma to predict both rumination and catastrophizing in adolescents. Consistent with our hypotheses and previous findings (Zannas et al., 2016), CATT haplotype carriers exposed to higher levels of childhood trauma reported higher levels of both rumination and catastrophizing, whereas this pattern was not observed in non-carriers. As noted previously, rumination and catastrophizing have been identified as transdiagnostic risk
Role of funding source
This work was supported by the Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) within the project “Prevention of depression in Portuguese adolescents: efficacy study of an intervention with adolescents and parents” (PTDC/MHC-PCL/4824/2012) and in part by an ERC starting grant, G × E molmech, grant number 281338 to EBB and the Fuqua family foundations.
Conflict of interest/disclosure
WEC is a board member of Hugarheill ehf, an Icelandic company dedicated to the prevention of depression, and he receives book royalties from John Wiley & Sons. His research is also supported by the NIH, the Mary and John Brock Foundation, and the Fuqua family foundations. He is a consultant to the George West Mental Health Foundation that oversees Skyland Trail, a residential treatment facility in Atlanta, Georgia.
EBB is co-inventor on FKBP5: a novel target for antidepressant therapy, European
Acknowledgements
We would like to thank the adolescents who gave their time to participate in this study. We would also like to thank the assessors at the University of Coimbra and technicians involved in the processing of the genetic data at the Max Planck Institute of Psychiatry.
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2019, PsychoneuroendocrinologyCitation Excerpt :SNP rs4713916 was in modest LD with the LD block (r² ≥ .55). This LD structure has also been found in previous studies (e.g., Halldorsdottir et al., 2017; Scheuer et al., 2016; Zimmermann et al., 2011) and is depicted in Supplementary Fig. S.1. The CATT haplotypes derived from the four SNPs forming a LD block (rs3800373, rs9296158, rs1360780, rs9470080) were computed using PLINK and the number of copies (0, 1, 2) of the CATT haplotype was calculated for each participant.
Cortisol awakening response is decreased in patients with first-episode psychosis and increased in healthy controls with a history of severe childhood abuse
2019, Schizophrenia ResearchCitation Excerpt :This divergent effect shown by patients and controls may be the consequence of a combination of genetic predisposition and social characteristics/environment of individuals vulnerable to psychosis which may impact the way the HPA axis modifies cortisol production in response to extreme stress (Miller et al., 2007; Morgan and Gayer-Anderson, 2016). For example in PTSD and depression, mutations of the FK506-binding protein (which modulates the activity of the glucocorticoid receptors) have been associated with increased risk of depression and PTSD in the presence of childhood abuse (Zannas et al., 2016; Halldorsdottir et al., 2017). Supporting this hypothesis, the increased risk of developing psychosis after exposure to early physical abuse in the AESOP study was lower among participants who had a large support network (Gayer-Anderson et al., 2015).
Childhood trauma in mood disorders: Neurobiological mechanisms and implications for treatment
2019, Pharmacological ReportsCitation Excerpt :Previously, it was shown that polymorphisms in FKBP5 are associated with a greater number of depressive episodes [58]. Recently, it was observed that, in adolescents, the FKBP5 gene moderates the relationship between negative childhood experiences and dysfunctional emotional regulation [59]. Another gene connected with the HPA axis is the corticotropin-releasing hormone type 1 receptor (CRHR1) gene.
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These authors contributed equally to the project.