Biomarkers for diagnosing post traumatic stress disorder
Inventors
Pollard, Harvey B. • DALGARD, Clifton L.
Assignees
Uniformed Services University of Health Sciences • Henry M Jackson Foundation for Advancedment of Military Medicine Inc
Publication Number
US-11085934-B2
Publication Date
2021-08-10
Expiration Date
2036-10-06
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Abstract
The invention relates to methods of determining if a subject is at risk of developing post-traumatic stress disorder (PTSD).
Core Innovation
The invention relates to methods of determining if a subject is at risk of developing post-traumatic stress disorder (PTSD) by assessing biomarkers in biological samples. Specifically, the methods comprise determining the ratio of monocyte chemoattractant protein 4 (MCP-4) to monocyte chemoattractant protein 1 (MCP-1), referred to as the MCP-4/MCP-1 ratio (MMR), and comparing this ratio to a normal MMR. An elevation in the MMR over normal ratios is indicative of an increased risk of PTSD or presence of PTSD. Additionally, the invention includes methods for monitoring the progression of PTSD by measuring the MMR over time and diagnosing PTSD in male or female subjects by measuring sex-specific markers such as MCP-1 and TARC in males or MCP-4 and MIP-1β in females.
The problem being solved addresses the need for objective, quantitative biomarkers for PTSD diagnosis and monitoring. Prior studies showed inconsistent cytokine or chemokine involvement, and PTSD diagnosis often relies on subjective clinical assessments. The invention identifies the disordered circadian pattern and elevated ratio of MCP-4/MCP-1 as a time-independent bivariate plasma biomarker for PTSD, which can stratify PTSD from healthy controls at multiple time points. It further addresses sex differences in biomarker profiles for PTSD, with specific proteins serving as diagnostic markers in males and females.
Claims Coverage
The independent claim covers a method for detecting specific proteins in male human subjects suspected of having PTSD, focusing on biomarker measurement and therapeutic intervention.
Detecting biomarkers MCP-1 and TARC in male plasma for PTSD risk
Obtaining a biological plasma sample from a male human subject suspected to have PTSD and measuring the levels of monocyte chemoattractant protein 1 (MCP-1) with SEQ ID NO:1 or NO:2 and thymus activation-regulated chemokine (TARC) with SEQ ID NO:3 or NO:4 in the plasma sample.
Comparing measured biomarker levels to established normal levels
Determining normal levels of MCP-1 and TARC from at least one previous plasma sample from the same subject or from biological samples of a population of male individuals without PTSD and comparing measured levels to these normal levels to identify decreases indicative of increased PTSD risk.
Administering selective serotonin reuptake inhibitors upon detection
Administering at least one SSRI selected from citalopram, dapoxetine, escitalopram, fluoxetine, fluvoxamine, indalpine, paroxetine, sertraline, and zimelidine to the male subject when decreased levels of MCP-1 and TARC compared to normal levels are detected.
Obtaining plasma samples at specific time points
Collecting plasma samples from the male subject at one or more time points including 2:00 a.m. (0200 hours) and/or 9:00 a.m. (0900 hours).
Applying biomarker detection post-depressive disorder diagnosis or treatment
Determining MCP-1 and TARC levels in subjects previously diagnosed with or treated for depressive disorder prior to PTSD biomarker assessment.
Using previous biological samples for normal level baseline
Using biological samples obtained from the male human subject prior to suspected onset of PTSD for establishing baseline normal MCP-1 and TARC levels.
The claims provide a method for diagnosing PTSD risk and treatment in male subjects by measuring specific chemokines MCP-1 and TARC at defined time points, comparing against normal baselines, and administering SSRIs upon detection of decreased biomarker levels indicative of PTSD risk.
Stated Advantages
The MCP-4/MCP-1 ratio serves as a quantitative, time-independent biomarker for PTSD, measurable at any blood draw time.
The biomarker reflects disease-specific alterations independent of circadian biology defects.
Disordered circadian rhythms of MCP-4 and MCP-1 provide diagnostic insight into PTSD.
Sex-specific biomarkers allow tailored diagnosis in male and female subjects.
The use of plasma biomarkers allows non-invasive testing for PTSD risk and monitoring.
Documented Applications
Determining if a subject is at risk of developing PTSD by measuring plasma MCP-4/MCP-1 ratio.
Diagnosing PTSD in male subjects by measuring MCP-1 and TARC levels.
Diagnosing PTSD in female subjects by measuring MCP-4 and MIP-1β levels.
Monitoring progression of PTSD through repeated measurement of MCP-4/MCP-1 ratio, TARC and MIP-1β levels over time.
Treating subjects diagnosed with PTSD with SSRIs guided by biomarker detection.
Using kits comprising antibodies targeting MCP-1, MCP-4, TARC, and MIP-1β for diagnosis and monitoring.
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