The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1β is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy.
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Dalgard
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Eidelman
Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Henry M. Jackson Foundation for Military Medicine, Bethesda, MD, USA.
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Jozwik
Department of Preventive Medicine and Biometrics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Olsen
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Srivastava
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Biswas
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Eudy
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Rothwell
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Mueller
Mood and Anxiety Disorders Branch, National Institute for Mental Health, Bethesda, MD, USA.
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Yuan
Janssen Research & Development, LLC, of Johnson and Johnson, Titusville, NJ, USA.
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Drevets
Janssen Research & Development, LLC, of Johnson and Johnson, Titusville, NJ, USA.
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Manji
United States Department of Defense, Washington, DC, USA.
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Vythlingam
Office of the Dean, Mount Sinai Medical School, New York, NY, USA.
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Charney
Mitsubishi Tanabe Pharma Development America, Jersey City, NJ, USA.
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Neumeister
Department of Psychiatry, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Center for the Study of Traumatic Stress, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Ursano
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Jacobowitz
Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Collaborative Health Initiative Research Program (CHIRP), Uniformed Services University School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
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Pollard
Department of Psychiatry, Hadassah Medical Center, Jerusalem, Israel.
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Bonne
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D054414:Chemokine CCL17 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000378:metabolism; D002908:Chronic Disease; D002940:Circadian Rhythm; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D012737:Sex Factors; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism*
D015415:Biomarkers; C099677:CCL13 protein, human; C106230:CCL17 protein, human; C111835:CCL2 protein, human; D054414:Chemokine CCL17; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins