{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "James J. Peters VA Medical Center, Bronx, NY, USA.",
    "Icahn School of Medicine at Mount Sinai, Mount Sinai, NY, USA.",
    "Integrative Systems Biology Branch, Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, MD, USA.",
    "James J. Peters VA Medical Center, Bronx, NY, USA. Rachel.Yehuda@mssm.edu.",
    "Icahn School of Medicine at Mount Sinai, Mount Sinai, NY, USA. Rachel.Yehuda@mssm.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Changxin Xu",
      "orcid": "0009-0000-3171-6093"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Heather N Bader",
      "orcid": "0009-0001-0640-9822"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Janine D Flory",
      "orcid": "0000-0002-9288-2068"
    },
    {
      "affs": [
        0
      ],
      "name": "Linda M Bierer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mitali Chattopadhyay"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Frank Desarnaud",
      "orcid": "0000-0002-3800-4010"
    },
    {
      "affs": [
        2
      ],
      "name": "Ruoting Yang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Amy Lehrner"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Iouri Makotkine"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Rachel Yehuda",
      "orcid": "0000-0001-8307-677X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fcg8n538kqz4z.bib",
  "cited_by": 0,
  "doi": "10.1038/s41398-026-04289-8",
  "fulltext_url": "https://europepmc.org/articles/PMC13680502",
  "id": "fcg8n538kqz4z",
  "issns": [
    "2158-3188"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897160",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC321-571"
    ],
    [
      "openalex",
      "3203|Posttraumatic Stress Disorder Research"
    ]
  ],
  "openalex": "W7170195796",
  "pdf_url": "https://europepmc.org/articles/PMC13680502?pdf=render",
  "pmcid": "PMC13680502",
  "pmid": "42897160",
  "published": "2026-07-01",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/fcg8n538kqz4z.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42897160",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897160"
    },
    {
      "first_seen": "2026-10-30T13:46:21Z",
      "native_id": "6260e2b5e9fb45538cc3c4533ba9dffa",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41398-026-04289-8"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3203|Posttraumatic Stress Disorder Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "Dynamic gene expression signatures predict psychotherapy response in PTSD.",
  "title_text": "Dynamic gene expression signatures predict psychotherapy response in PTSD.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:21Z",
  "url": "https://research.draconitic.com/paper/fcg8n538kqz4z",
  "venue": "Translational psychiatry",
  "versions": []
}