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.
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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