Genetics of glucocorticoid regulation and posttraumatic stress disorder--What do we know?
Level 5 - mechanism / opinion, no new human data
Narrative review of genetic and mechanistic studies with no new data or systematic search methodology
PubMed 26872620 · doi:10.1016/j.neubiorev.2016.02.005
What was done
This review evaluated literature on genetic factors regulating glucocorticoid function and hypothalamic-pituitary-adrenal (HPA) axis reactivity in posttraumatic stress disorder (PTSD). It focused on pathways involving corticotrophin-releasing hormone, arginine vasopressin/oxytocin, the glucocorticoid receptor (GR), and the co-chaperone FKBP5, as well as gene-environment interactions and epigenetic mechanisms.
What was found
The abstract notes that genetic factors are estimated to account for 30% of the variance in PTSD risk. Specific associations include the GR gene single nucleotide polymorphism (SNP) BclI being linked to glucocorticoid hypersensitivity and PTSD symptoms, FKBP5 gene SNPs interacting with childhood adversity to moderate PTSD risk (with rs9470080 independently associated with lifetime PTSD), and SNPs in the CRHR1 gene also associating with PTSD risk. No numerical effect sizes, sample counts, or p-values were provided in the abstract.
Why it matters
Understanding genetic variations that alter glucocorticoid receptor sensitivity helps explain individual differences in vulnerability to PTSD following traumatic events and underscores the role of gene-environment interactions.
Limits
The abstract provides no quantitative effect sizes, confidence intervals, or participant counts. As a narrative review, it lacks systematic search criteria or meta-analytic pooling, and the summarized candidate-gene associations are subject to known confounding and replication challenges.
Cited by
- supports Variations in glucocorticoid-pathway genes including NR3C1, FKBP5, and CRHR1 impair cortisol receptor signaling and increase vulnerability to PTSD and depression.