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Dynamic immune and metabolic dysregulation in women with post-traumatic stress disorder: Longitudinal transcriptomic insights following sexual assault

Molecular Psychiatry (2026) Cite this article

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Abstract

Post-traumatic stress disorder (PTSD) is a chronic and debilitating psychiatric condition, and sexual assault represents the leading risk factor for PTSD in women, with up to 50% of survivors developing the disorder. However, most transcriptomic studies have focused on male military veterans, limiting insight into the molecular mechanisms underlying PTSD in women. We conducted a longitudinal RNA sequencing study of blood samples from 65 women with PTSD and 65 healthy controls (HC). One-year follow-up assessments were performed in 35 PTSD participants after completion of treatment with either sertraline or Interpersonal Psychotherapy adapted for PTSD (IPT-PTSD), and in 12 HC participants, who did not receive treatment but were reassessed for longitudinal comparison of transcriptomic profiles. Differential gene expression analyses were conducted across diagnostic groups (PTSD vs HC), symptom trajectories (persistent vs remitting), and treatment arms (sertraline vs IPT-PTSD), using both cross-sectional and longitudinal designs. Pathway enrichment and co-expression network analyses were performed to identify dysregulated biological processes and gene modules. At baseline, women with PTSD exhibited downregulation of immune-related pathways and upregulation of erythropoietic and metabolic processes compared to HC, consistent with systemic immune suppression and compensatory transcriptomic adaptations. Persistent PTSD was characterized by sustained immune suppression, dysregulated apoptotic signaling, and elevated mitochondrial activity, whereas the remitting trajectory showed upregulation of immune response and cell communication pathways, suggesting partial immune restoration. Comparing PTSD cases at baseline and after one year of treatment, both sertraline and IPT-PTSD were associated with overlapping transcriptomic changes, suggesting shared molecular mechanisms. Overall, this study reveals dynamic peripheral transcriptomic dysregulation in women with PTSD. Although we cannot fully disentangle whether these changes reflect the disorder itself or traumatic exposure, our findings identify molecular signatures of symptom persistence, remission, and treatment response, supporting the potential utility of transcriptomic biomarkers to inform therapeutic strategies.

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Fig. 1: Heatmap of the top 30 genes from the cross-sectional comparison between individuals with PTSD and healthy controls (HC) at baseline.
The alternative text for this image may have been generated using AI.
Fig. 2: Transcriptomic profiles of women with PTSD compared to healthy controls (HC) at baseline.
The alternative text for this image may have been generated using AI.
Fig. 3: Gene set enrichment analysis (GSEA) of Gene Ontology Biological Process (GO:BP) terms across PTSD symptom trajectories.
The alternative text for this image may have been generated using AI.
Fig. 4: Longitudinal co-expression and enrichment analyses of gene expression changes in PTSD.
The alternative text for this image may have been generated using AI.

Data availability

The RNA sequencing data generated in this study have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE318733. The dataset is currently available for review using the following access token: qpenyoiyvxqrdav. The data will be made publicly available upon publication.

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Acknowledgements

The authors thank all participants and staff involved in the development and implementation of this cohort study. We also acknowledge the Programa de Atendimento a Vítimas de Violência e Estresse (PROVE) and the Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP) for their support.

Funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; grants 2014/12559-5 and 2015/26473-8) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Finance Code 001).

Author information

Authors and Affiliations

  1. Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo, São Paulo, Brazil

    Amanda Victória Gomes Bugiga, Vanessa Kiyomi Ota, Gustavo Satoru Kajitani, Beatriz Enguidanos Villena Rueda, Joice Santos Rosa, Adrielle Martins Oliveira, Carolina Muniz Carvalho & Sintia Iole Belangero

  2. Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil

    Amanda Victória Gomes Bugiga, Vanessa Kiyomi Ota, Gustavo Satoru Kajitani, Beatriz Enguidanos Villena Rueda, Carolina Muniz Carvalho & Sintia Iole Belangero

  3. Programa de Pós-Graduação em Biologia Estrutural e Funcional, Universidade Federal de São Paulo, São Paulo, Brazil

    Amanda Victória Gomes Bugiga, Gustavo Satoru Kajitani, Beatriz Enguidanos Villena Rueda, Carolina Muniz Carvalho & Sintia Iole Belangero

  4. Center for Molecular Oncology, Hospital Sírio-Libanês, São Paulo, Brazil

    Gabriela Der Agopian Guardia, Paula Fontes Asprino & Pedro Alexandre Favoretto Galante

  5. Programa de Pós-Graduação em Psiquiatria e Psicologia Médica, Universidade Federal de São Paulo, São Paulo, Brazil

    Joice Santos Rosa, Adrielle Martins Oliveira, Bruno Messina Coimbra, Andrea Feijó Mello, Marcelo Feijó Mello & Sintia Iole Belangero

  6. Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health and Global Health Research Institute, Amsterdam, The Netherlands

    Bruno Messina Coimbra

  7. Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, Brazil

    Marcelo Feijó Mello

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  1. Amanda Victória Gomes Bugiga
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  3. Gustavo Satoru Kajitani
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  4. Gabriela Der Agopian Guardia
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  5. Beatriz Enguidanos Villena Rueda
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  6. Joice Santos Rosa
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  11. Andrea Feijó Mello
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  12. Carolina Muniz Carvalho
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  13. Marcelo Feijó Mello
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  14. Sintia Iole Belangero
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Contributions

A.V.G.B.: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing – original draft. V.K.O.: Data curation, Formal analysis, Investigation, Methodology, Writing – review & editing. G.S.K.: Data curation, Formal analysis, Investigation, Methodology, Writing – review & editing. G.D.A.G.: Formal analysis, Investigation, Methodology. B.E.V.R.: Formal analysis, Investigation, Methodology. J.S.R.: Writing – review & editing. A.M.O.: Formal analysis, Investigation, Methodology. B.M.C.: Conceptualization, Resources, Supervision, Writing – review & editing. P.F.A.: Investigation, Methodology, Resources. P.A.F.G.: Formal analysis, Investigation, Methodology. A.F.M.: Conceptualization, Resources, Supervision, Writing – review & editing. C.M.C.: Conceptualization, Resources, Supervision, Writing – review & editing. M.F.M.: Conceptualization, Resources, Supervision, Writing – review & editing. S.I.B.: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing.

Corresponding author

Correspondence to Sintia Iole Belangero.

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The authors report no conflicts of interest.

Ethics statement

This study was approved by the Ethics Committee of the Universidade Federal de São Paulo (CAAE: 30332214.8.0000.5505). All participants provided written informed consent. All methods were performed in accordance with relevant guidelines and regulations.

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Bugiga, A.V.G., Ota, V.K., Kajitani, G.S. et al. Dynamic immune and metabolic dysregulation in women with post-traumatic stress disorder: Longitudinal transcriptomic insights following sexual assault. Mol Psychiatry (2026). https://doi.org/10.1038/s41380-026-03639-8

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