Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients.
A significant main effect of FKBP5rs1360780 and PTSD and an interaction effect between genotype and PTSD status were found on mean FKBP5 DNA methylation level.
A significant gene-level GxE gene effect was demonstrated for FKBP5 when pooled across all four examined variants (rs1360780, rs3800373, rs9296158, rs9470080) when interacting with trauma exposure on PTSD.
The FK506-binding protein 51 (FKBP51) has emerged as a key regulator of endocrine stress responses in mammals and as a potential therapeutic target for stress-related disorders (depression, post-traumatic stress disorder), metabolic disorders (obesity and diabetes) and chronic pain.
Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.
There is strong evidence suggesting altered regulation of steroid receptor hormones by chaperones, particularly the 51 kDa FK506-binding protein (FKBP51), may work with environmental factors to increase susceptibility to various psychiatric illnesses including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and anxiety.
Study 1 (Humans) examines if FKBP5 single nucleotide polymorphisms (SNPs) and PTSD symptom domains (re-experiencing, avoidance/numbing, hyperarousal) are associated with abnormal fear extinction phenotypes identified using latent growth mixture modeling (LGMM).
The results of these studies suggest that several polymorphisms in the HPA axis genes, including FKBP5, NR3C1, CRHR1, and CRHR2, may be risk factors for PTSD development or may be associated with the severity of PTSD symptoms.
Our findings demonstrate that lowering FKBP5 expression in IL is sufficient to both reduce fear acquisition and enhance extinction, and suggest that lower expression of FKBP5 in the ventral medial prefrontal cortex could contribute to resiliency to PTSD.
In this review, the major existing rodent models of PTSD are reviewed in terms of validity, advantages and limitations; moreover, significant results and implications for future research-such as the role of FKBP5, a mediator of the glucocorticoid stress response and promising target for therapeutic interventions-are discussed.
In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD.
There were 448 differentially expressed genes in the discovery cohort, of which 99 remained significant in the replication cohort, including FKBP5, which was found to be up-regulated in current PTSD regardless of the genotypes.
Single nucleotide polymorphisms (SNPs) in the FKBP5 gene are associated with altered hypothalamus-pituitary-adrenal (HPA) axis function, changes in the structure and function of several cognitive brain areas, and increased susceptibility to post-traumatic stress disorder, major depression, bipolar disorder and suicidal events.
They further indicate that FKBP5 polymorphisms and childhood abuse may contribute to vulnerability for PTSD symptoms and may be most strongly associated with trauma-related hyperarousal symptoms that comprise this phenotype.
However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5.This was the goal of the present study.
The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder.
FKBP5 gene SNPs interacted with childhood adversity to moderate PTSD risk and in particular, the rs9470080 SNP was independently associated with lifetime PTSD.
FK506 binding protein (FKBP5) is a negative regulator of cortisol response, FKBP5 methylation has been linked to brain morphology and mental disorder risk, and genetic variation of FKBP5 was associated with post-traumatic stress disorder in adults.