Internet-delivered cognitive behavioral therapy is associated with distinct blood small RNA profiles in panic disorder

Vaknine Treidel, S.; Halaj, A.; Mitzva, L.; Goltser-Dubner, T.; Strauss, A.; Gelchinsky-Karagichev, B.; Pevzner, D.; Oz, O.; Amer, R.; Lavon, M.; Gadish, O.; Bennett, E. R.; Greenberg, D. S.; Carmel, L.; Israel, S.; Segman, R.; Huppert, J. D.; Soreq, H.

doi:10.64898/2026.09.03.749122

bioRxiv · 10.64898/2026.09.03.749122

Internet-delivered cognitive behavioral therapy is associated with distinct blood small RNA profiles in panic disorder

Vaknine Treidel, S.·Halaj, A.·Mitzva, L.·Goltser-Dubner, T.·Strauss, A.·Gelchinsky-Karagichev, B.·Pevzner, D.·Oz, O.·Amer, R.·Lavon, M.·Gadish, O.·Bennett, E. R.·Greenberg, D. S.·Carmel, L.·Israel, S.·Segman, R.·Huppert, J. D.·Soreq, H.

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Abstract

Panic disorder associates with altered fear circuitry, autonomic dysregulation and stress-related immune perturbations, yet its molecular and treatment-response signatures remain poorly defined. Internet-delivered cognitive behavioral therapy (iCBT) is an effective first-line treatment with unexplained outcome variations across individuals. Here, we report altered profiles of small non-coding RNAs in peripheral blood mononuclear cells from panic disorder patients before and after iCBT, compared with longitudinally sampled healthy controls. Thirteen top-ranking microRNAs discriminated patients from controls and separated pre- and post-treatment states, both of which differed from controls. Correspondingly, baseline hsa-miR-125b-5p levels were significantly associated with post-iCBT symptom improvement. Transfer RNA-derived fragments (tRFs) showed even greater discriminatory power, with nuclear-Val-3'-tRF family members exhibiting a pronounced post-treatment shift. Pathway analyses of panic disorder-associated and CBT-responsive small RNA targets converged on immune-related pathways, supporting a role in inflammatory mechanisms and highlighting blood small non-coding RNAs as promising biomarkers of panic disorder and its therapeutic response.

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Vaknine Treidel, S., Halaj, A., Mitzva, L., Goltser-Dubner, T., Strauss, A., Gelchinsky-Karagichev, B., Pevzner, D., Oz, O., Amer, R., Lavon, M., Gadish, O., Bennett, E. R., Greenberg, D. S., Carmel, L., Israel, S., Segman, R., Huppert, J. D., Soreq, H.. 2026-09-07. Internet-delivered cognitive behavioral therapy is associated with distinct blood small RNA profiles in panic disorder. https://doi.org/10.64898/2026.09.03.749122

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