Imaging brain cortisol regulation in PTSD with a target for 11β-hydroxysteroid dehydrogenase type 1

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Abstract

BACKGROUND Investigations of stress dysregulation in posttraumatic stress disorder (PTSD) have focused on peripheral cortisol, but none have examined cortisol in the human brain. This study used positron emission tomography (PET) to image 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol-producing enzyme, as a putative brain cortisol marker in PTSD.METHODS Sixteen individuals with PTSD and 17 healthy, trauma-exposed controls (TCs) underwent PET imaging with [18F]AS2471907, a radioligand for 11β-HSD1.RESULTS Prefrontal-limbic 11β-HSD1 availability, estimated as [18F]AS2471907 volume of distribution (VT), was significantly higher in the PTSD group compared with the TC group (β = 1.16, P = 0.0057). Lower prefrontal-limbic 11β-HSD1 availability was related to greater overall PTSD severity (R2 = 0.27, P = 0.038) in the PTSD group. 11β-HSD1 availability was not related to plasma cortisol levels (R2 = 0.026, P = 0.37). In a PTSD subset (n = 10), higher 11β-HSD1 availability was associated with higher availability of translocator protein (TSPO), a microglial marker (β = 4.40, P = 0.039).CONCLUSION Higher brain cortisol–producing 11β-HSD1 in the PTSD group may represent a resilience-promoting neuroadaptation resulting in lower PTSD symptoms. Along with preliminary associations between 11β-HSD1 and TSPO, corroborating previous evidence of immune suppression in PTSD, these findings collectively challenge previous hypotheses of the deleterious effects of both excessive brain glucocorticoid and brain immune signaling in PTSD.FUNDING Brain and Behavior Research Foundation Independent Investigator Grant, National Institute of Mental Health grants F30MH116607 and R01MH110674, the Veterans Affairs National Center for PTSD, the Gustavus and Louise Pfeiffer Foundation Fellowship, Clinical and Translational Science Awards grant UL1 TR000142 from the NIH National Center for Advancing Translational Science.

Authors

Shivani Bhatt, Ansel T. Hillmer, Aleksandra Rusowicz, Nabeel Nabulsi, David Matuskey, Gustavo A. Angarita, Soheila Najafzadeh, Michael Kapinos, Steven M. Southwick, John H. Krystal, Richard E. Carson, Yiyun Huang, Kelly P. Cosgrove