Background: Patients with post-traumatic stress disorder (PTSD) show a different stress-related cognitive style compared with healthy controls (HC). The FK506 binding protein 5 gene (FKBP5), one of the PTSD known risk factors, is involved in the stress response through the hypothalamic-pituitary-adrenal axis and brain volumetric alterations. The present study aimed to uncover the neural correlates of stress-related cognitive styles through the analysis of the regional brain volumes and FKBP5 genotype in patients with PTSD compared with HC.
Methods: In this study, 51 patients with PTSD and 94 HC were assessed for stress-related cognitive styles, PTSD symptoms severity, and genotype of FKBP5 single nucleotide polymorphisms, and underwent T1-weighted structural magnetic resonance imaging. Diagnosis-by-genotype interaction for regional brain volumes was examined in 16 brain regions of interest.
Results: Patients with PTSD showed significantly higher levels of catastrophizing, ruminative response, and repression, and reduced distress aversion and positive reappraisal compared with HC (p < 0.001). Significant diagnosis-by-genotype interactions for regional brain volumes were observed for bilateral hippocampi and left frontal operculum. A significant positive correlation between the severity of the repression and left hippocampal volume was found in a subgroup of patients with PTSD with FKBP5 rs3800373 (AA genotype) or rs1360780 (CC genotype).
Conclusions: The present study showed the influences of FKBP5 genotype on the distorted cognitive styles in PTSD by measuring the volumetric alteration of hippocampal regions, providing a possible role of the hippocampus and left frontal operculum as significant neurobiological correlates of PTSD.
Keywords: FK506 binding protein 5 gene (FKBP5); hippocampus; post-traumatic stress disorder; stress-related cognitive style.