Dynamic gene expression signatures predict psychotherapy response in PTSD.
5 affiliations
- 1James J. Peters VA Medical Center, Bronx, NY, USA.
- 2Icahn School of Medicine at Mount Sinai, Mount Sinai, NY, USA.
- 3Integrative Systems Biology Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
- 4James J. Peters VA Medical Center, Bronx, NY, USA. [email protected].
- 5Icahn School of Medicine at Mount Sinai, Mount Sinai, NY, USA. [email protected].
Abstract
Static blood-based biomarkers provide limited insight into psychiatric illness and recovery, largely because they capture only a single, unperturbed snapshot of inherently dynamic biological systems. In this study, we applied a dynamic, longitudinal dual-state approach to characterize peripheral blood mononuclear cell (PBMC) transcriptional trajectories associated with psychotherapy outcomes in post-traumatic stress disorder (PTSD). PBMC transcriptional profiles were generated for veterans with PTSD (n = 46, 21, and 17, respectively) and controls (n = 26, 26, and 23) at pre-treatment, post-treatment, and follow-up. The PTSD cohort with profiles across all three timepoints was divided into responders (n = 6) and non-responders (n = 11) based on their Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) trajectories. All subjects were profiled in both unstimulated and dexamethasone-stimulated states. At pre-treatment, unstimulated responders and non-responders exhibited pronounced transcriptional differences exceeding those observed between PTSD and controls. Longitudinally, unstimulated responders showed a marked shift toward control-like profiles, whereas non-responders retained persistent divergence. Pathway analyses identified a prominent temporal signal within Class C/3 G-protein-coupled receptor pathways driven largely by bitter taste receptors (TAS2Rs), along with subgroup-specific regulation of GABAB, opioid, and NMDA receptor signaling. Dexamethasone-induced responses further differentiated subgroups and showed opposing associations with recovery trajectories, implicating glucocorticoid sensitivity as a potential predictor of treatment outcomes. These findings indicate that biological responsiveness itself constitutes a measurable phenotype of recovery, and that dynamic functional profiling of living immune cells can reveal clinically relevant trajectories and candidate mechanisms not accessible through static biomarkers.
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BibTeX
@article{xu2026dynamic,
title = {{Dynamic gene expression signatures predict psychotherapy response in PTSD.}},
author = {Changxin Xu and Heather N Bader and Janine D Flory and Linda M Bierer and Mitali Chattopadhyay and Frank Desarnaud and Ruoting Yang and Amy Lehrner and Iouri Makotkine and Rachel Yehuda},
journal = {Translational psychiatry},
year = {2026},
month = jul,
doi = {10.1038/s41398-026-04289-8},
url = {https://europepmc.org/article/MED/42897160},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Dynamic gene expression signatures predict psychotherapy response in PTSD.
AU - Changxin Xu
AU - Heather N Bader
AU - Janine D Flory
AU - Linda M Bierer
AU - Mitali Chattopadhyay
AU - Frank Desarnaud
AU - Ruoting Yang
AU - Amy Lehrner
AU - Iouri Makotkine
AU - Rachel Yehuda
PY - 2026
DA - 2026/07/01
JO - Translational psychiatry
DO - 10.1038/s41398-026-04289-8
UR - https://europepmc.org/article/MED/42897160
AB - Static blood-based biomarkers provide limited insight into psychiatric illness and recovery, largely because they capture only a single, unperturbed snapshot of inherently dynamic biological systems. In this study, we applied a dynamic, longitudinal dual-state approach to characterize peripheral blood mononuclear cell (PBMC) transcriptional trajectories associated with psychotherapy outcomes in post-traumatic stress disorder (PTSD). PBMC transcriptional profiles were generated for veterans with PTSD (n = 46, 21, and 17, respectively) and controls (n = 26, 26, and 23) at pre-treatment, post-treatment, and follow-up. The PTSD cohort with profiles across all three timepoints was divided into responders (n = 6) and non-responders (n = 11) based on their Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) trajectories. All subjects were profiled in both unstimulated and dexamethasone-stimulated states. At pre-treatment, unstimulated responders and non-responders exhibited pronounced transcriptional differences exceeding those observed between PTSD and controls. Longitudinally, unstimulated responders showed a marked shift toward control-like profiles, whereas non-responders retained persistent divergence. Pathway analyses identified a prominent temporal signal within Class C/3 G-protein-coupled receptor pathways driven largely by bitter taste receptors (TAS2Rs), along with subgroup-specific regulation of GABAB, opioid, and NMDA receptor signaling. Dexamethasone-induced responses further differentiated subgroups and showed opposing associations with recovery trajectories, implicating glucocorticoid sensitivity as a potential predictor of treatment outcomes. These findings indicate that biological responsiveness itself constitutes a measurable phenotype of recovery, and that dynamic functional profiling of living immune cells can reveal clinically relevant trajectories and candidate mechanisms not accessible through static biomarkers.
SN - 2158-3188
ER -