Abstract
The FKBP5 gene, a glucocorticoid receptor (GR)-regulating co-chaperone of stress proteins, is of special interest because of its role in hypothalamic-pituitary-adrenal (HPA)-axis regulation. However, studies finding a genetic relationship between posttraumatic stress disorder (PTSD) and the FKBP5 gene have failed to distinguish between the development and persistence of PTSD, thereby limiting the prognostic usefulness of such a finding. The present study sought to longitudinally explore this question by examining the association between four single-nucleotide polymorphisms (SNPs) in the FKBP5 gene (rs3800373, rs9470080, rs1360780, and rs9296158), the persistence of PTSD (severity and diagnostic status), and memory performance among twenty-two treatment-seekers diagnosed with acute PTSD. Results showed that the four SNPs significantly interacted with improvement in PTSD symptoms as well as PTSD diagnostic status. Individuals homozygous for the dominant allele and having experienced higher levels of peritraumatic responses subsequently showed more memory dysfunction. The results of this study suggest that SNPs in the FKBP5 gene are associated with symptom persistence and memory dysfunction in acute PTSD.
Highlights
There are two important questions when trying to understand Posttraumatic Stress Disorder (PTSD) [1].The first one is why do some trauma-exposed individuals develop the disorder while others do not?And the second one is why do some remit from the disorder while others do not? The latter echoes the observation that remission from PTSD in the months following exposure to traumatic stress is the norm [2], and that PTSD is considered a disorder of failed recovery [3].In a related vein, from a conceptual point of view, a good predictor of the development of PTSD should be a poor predictor of its persistence, as many PTSD cases remit within the first year or so [4,5]
We hypothesized that (i) there would be an association between PTSD diagnostic status measured 9 months after trauma-exposure (i.e., 6 months after enrollment in the study) and the FKBP5 gene, thereby suggesting a G × E interaction conferring greater risk for chronicity of PTSD, all other variables being equal; that (ii) the FKBP5 gene would prospectively explain improvement in PTSD symptoms; and that (iii) subjective severity of trauma as measured by peritraumatic distress and dissociation and genetic influences (FKBP5) would have an interactive effect on endophenotypes such as memory dysfunction in chronic unremitting PTSD
A series of linear regression analyses were subsequently performed to explore the contribution of FKBP5 polymorphisms on the improvement in PTSD symptoms according to the Clinician-administered PTSD Scale (CAPS)
Summary
There are two important questions when trying to understand Posttraumatic Stress Disorder (PTSD) [1]. From a conceptual point of view, a good predictor of the development of PTSD should be a poor predictor of its persistence, as many PTSD cases remit within the first year or so [4,5]. If this account is correct, we would expect to find different sets of gene x environment (G × E). It follows that genetic studies with a cross-sectional design cannot uncover such interactions [6] and that it is probably more important from a clinical perspective to uncover G × E interactions related to the persistence of the disorder. A literature search in popular databases such as PubMed or P.I.L.O.T.S. suggests that the role of G × E interactions in the development of PTSD—and even more so in its persistence—has been largely neglected far
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