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Decreased mononuclear cell NR3C1 SKA2 and FKPB5 expression levels among adult survivors of suicide bombing terror attacks in childhood are associated with the development of PTSD

Molecular Psychiatry volume 28, pages 3851–3855 (2023)Cite this article

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Abstract

Life threatening trauma and the development of PTSD during childhood, may each associate with transcriptional perturbation of immune cell glucocorticoid reactivity, yet their separable longer term contributions are less clear. The current study compared resting mononuclear cell gene expression levels of the nuclear receptor, subfamily 3, member 1 (NR3C1) coding the glucocorticoid receptor, its trans-activator spindle and kinetochore-associated protein 2 (SKA2), and its co-chaperon FKBP prolyl isomerase 5 (FKBP5), between a cohort of young adults first seen at the Hadassah Emergency Department (ED) after surviving a suicide bombing terror attack during childhood, and followed longitudinally over the years, and matched healthy controls not exposed to life threatening trauma. While significant reductions in mononuclear cell gene expression levels were observed among young adults for all three transcripts following early trauma exposure, the development of subsequent PTSD beyond trauma exposure, accounted for a small but significant portion of the variance in each of the three transcripts. Long-term perturbation in the expression of immune cell glucocorticoid response transcripts persists among young adults who develop PTSD following life threatening trauma exposure in childhood, denoting chronic dysregulation of immune stress reactivity.

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Fig. 1: Mononuclear cell transcript levels among early trauma vs. non-trauma exposed controls.
Fig. 2: Mononuclear cell transcript levels among subjects exposed to early trauma who did or did not develop PTSD, and non-trauma exposed controls.

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Funding

The study was supported in part by the Herman-Danna Foundation.

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Author notes

  1. These authors contributed equally: Tanya Goltser-Dubner, Amit Shalev, Esti Galili-Weisstub, Ronen Segman.

Authors and Affiliations

  1. Molecular Psychiatry Laboratory, Department of Psychiatry, Hadassah Medical Organization and Faculty of Medicine, Hebrew University, Jerusalem, Israel

    Tanya Goltser-Dubner, Maayan Yogev, Carmel Kalla, Dalya Pevzner, Osnat Oz, Chen Saloner, Reaan Amer, Michal Lavon, Amit Lotan & Ronen Segman

  2. The Herman-Danna Division of Pediatric Psychiatry, Department of Psychiatry, Hadassah Medical Organization and Faculty of Medicine, Hebrew University, Jerusalem, Israel

    Tanya Goltser-Dubner, Amit Shalev, Fortu Benarroch, Ranin Masarwa, Josef Martin, Esti Galili-Weisstub & Ronen Segman

  3. Department of Psychology, Hebrew University, Jerusalem, Israel

    Laura Canetti

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Contributions

RS, TGD, AS, FB, and EGW designed and guided the study. RS, AS, FB, EGW, CK, RM, JM, and CS participated in the clinical procedures. TGD, DP, OO, RA, and ML preformed the molecular work. TGD, LC, RS, and AL preformed the statistical analyses. TGD and RS wrote the manuscript with substantive edits from AS, EGW, and FB.

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Correspondence to Ronen Segman.

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Goltser-Dubner, T., Shalev, A., Benarroch, F. et al. Decreased mononuclear cell NR3C1 SKA2 and FKPB5 expression levels among adult survivors of suicide bombing terror attacks in childhood are associated with the development of PTSD. Mol Psychiatry 28, 3851–3855 (2023). https://doi.org/10.1038/s41380-023-02278-7

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