Transcriptional modulation of stress-related genes in association with early life stress exposure and trauma-focused psychotherapy in treatment-resistant depression patients

Early life stress (ELS) is associated with treatment-resistant depression (TRD), and trauma-focused psychotherapy benefits TRD patients exposed to ELS. We explored peripheral modulations of stress-response genes (nuclear receptor subfamily 3 group C member 1 [NR3C1], FK506-binding protein 5 [FKBP5], and serum/glucocorticoid-regulated kinase 1 [SGK1]) in relation to ELS and symptom changes during psychotherapy. Forty-one TRD patients participated and 21 patients underwent trauma-focused psychotherapy, comprising eye movement desensitization and reprocessing or trauma-focused cognitive behavioral therapy. We used the Montgomery-Åsberg Depression Rating Scale, the Beck Depression Inventory-II and the Beck Anxiety Inventory for symptom evaluation, the Childhood Experience of Care and Abuse Questionnaire for ELS assessment, and the quantitative reverse transcription polymerase chain reaction (RT-qPCR) for transcript analysis. We found higher NR3C1 and FKBP5 baseline mRNA levels in patients with maternal neglect. Trauma-focused psychotherapy induced modifications in transcripts’ levels and symptom amelioration along psychotherapy correlated with genes’ modulations. Transcript levels for all genes were higher in patients relapsing after 24 weeks.

Journal

English

Silva, Rosana Carvalho
Dattilo, Vincenzo
Perusi, Giulia
Mazzelli, Monica
Maffioletti, Elisabetta
Bazzanella, Roberta
Bortolomasi, Marco
Cattaneo, Annamaria
Gennarelli, Massimo
Minelli, Alessandra

Silva, R. C., Dattilo, V., Perusi, G., Mazzelli, M., Maffioletti, E., Bazzanella, R., Bortolomasi, M., ..Minelli, A. (2023).  Transcriptional modulation of stress-related genes in association with early life stress exposure and trauma-focused psychotherapy in treatment-resistant depression patients. Journal of EMDR Practice and Research,17(3), 119-138. doi:10.1891/EMDR-2023-0019