Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures
Abstract Background One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Military Medical Research |
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| Online Access: | https://doi.org/10.1186/s40779-023-00505-4 |
| _version_ | 1797355945347514368 |
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| author | Esha Sultana Nandan Shastry Rishabh Kasarla Jacob Hardy Fanny Collado Kristina Aenlle Maria Abreu Emily Sisson Kimberly Sullivan Nancy Klimas Travis J. A. Craddock |
| author_facet | Esha Sultana Nandan Shastry Rishabh Kasarla Jacob Hardy Fanny Collado Kristina Aenlle Maria Abreu Emily Sisson Kimberly Sullivan Nancy Klimas Travis J. A. Craddock |
| author_sort | Esha Sultana |
| collection | DOAJ |
| description | Abstract Background One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI. Methods Symptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using Analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups. Results GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both Healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F = 4.7, P = 0.01,) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F > 3.75, P < 0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms. Conclusion We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively. |
| first_indexed | 2024-03-08T14:18:28Z |
| format | Article |
| id | doaj.art-bc0e6750d1114d8a82a9e39e714fcc3a |
| institution | Directory Open Access Journal |
| issn | 2054-9369 |
| language | English |
| last_indexed | 2024-03-08T14:18:28Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
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| series | Military Medical Research |
| spelling | doaj.art-bc0e6750d1114d8a82a9e39e714fcc3a2024-01-14T12:16:23ZengBMCMilitary Medical Research2054-93692024-01-0111111510.1186/s40779-023-00505-4Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measuresEsha Sultana0Nandan Shastry1Rishabh Kasarla2Jacob Hardy3Fanny Collado4Kristina Aenlle5Maria Abreu6Emily Sisson7Kimberly Sullivan8Nancy Klimas9Travis J. A. Craddock10Institute for Neuro-Immune Medicine, Nova Southeastern UniversityInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityDepartment of Clinical Immunology, Nova Southeastern UniversityInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityDepartment of Environmental Health, Boston University School of Public HealthDepartment of Environmental Health, Boston University School of Public HealthInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityInstitute for Neuro-Immune Medicine, Nova Southeastern UniversityAbstract Background One-third of veterans returning from the 1990–1991 Gulf War reported a myriad of symptoms including cognitive dysfunction, skin rashes, musculoskeletal discomfort, and fatigue. This symptom cluster is now referred to as Gulf War Illness (GWI). As the underlying mechanisms of GWI have yet to be fully elucidated, diagnosis and treatment are based on symptomatic presentation. One confounding factor tied to the illness is the high presence of post-traumatic stress disorder (PTSD). Previous research efforts have demonstrated that both GWI and PTSD are associated with immunological dysfunction. As such, this research endeavor aimed to provide insight into the complex relationship between GWI symptoms, cytokine presence, and immune cell populations to pinpoint the impact of PTSD on these measures in GWI. Methods Symptom measures were gathered through the Multidimensional fatigue inventory (MFI) and 36-item short form health survey (SF-36) scales and biological measures were obtained through cytokine & cytometry analysis. Subgrouping was conducted using Davidson Trauma Scale scores and the Structured Clinical Interview for Diagnostic and statistical manual of mental disorders (DSM)-5, into GWI with high probability of PTSD symptoms (GWIH) and GWI with low probability of PTSD symptoms (GWIL). Data was analyzed using Analysis of variance (ANOVA) statistical analysis along with correlation graph analysis. We mapped correlations between immune cells and cytokine signaling measures, hormones and GWI symptom measures to identify patterns in regulation between the GWIH, GWIL, and healthy control groups. Results GWI with comorbid PTSD symptoms resulted in poorer health outcomes compared with both Healthy control (HC) and the GWIL subgroup. Significant differences were found in basophil levels of GWI compared with HC at peak exercise regardless of PTSD symptom comorbidity (ANOVA F = 4.7, P = 0.01,) indicating its potential usage as a biomarker for general GWI from control. While the unique identification of GWI with PTSD symptoms was less clear, the GWIL subgroup was found to be delineated from both GWIH and HC on measures of IL-15 across an exercise challenge (ANOVA F > 3.75, P < 0.03). Additional differences in natural killer (NK) cell numbers and function highlight IL-15 as a potential biomarker of GWI in the absence of PTSD symptoms. Conclusion We conclude that disentangling GWI and PTSD by defining trauma-based subgroups may aid in the identification of unique GWI biosignatures that can help to improve diagnosis and target treatment of GWI more effectively.https://doi.org/10.1186/s40779-023-00505-4Gulf War IllnessPost-traumatic stress disorderCytokine signallingFlow cytometryCorrelation networksComplete blood count |
| spellingShingle | Esha Sultana Nandan Shastry Rishabh Kasarla Jacob Hardy Fanny Collado Kristina Aenlle Maria Abreu Emily Sisson Kimberly Sullivan Nancy Klimas Travis J. A. Craddock Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures Military Medical Research Gulf War Illness Post-traumatic stress disorder Cytokine signalling Flow cytometry Correlation networks Complete blood count |
| title | Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures |
| title_full | Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures |
| title_fullStr | Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures |
| title_full_unstemmed | Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures |
| title_short | Disentangling the effects of PTSD from Gulf War Illness in male veterans via a systems-wide analysis of immune cell, cytokine, and symptom measures |
| title_sort | disentangling the effects of ptsd from gulf war illness in male veterans via a systems wide analysis of immune cell cytokine and symptom measures |
| topic | Gulf War Illness Post-traumatic stress disorder Cytokine signalling Flow cytometry Correlation networks Complete blood count |
| url | https://doi.org/10.1186/s40779-023-00505-4 |
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