MicroRNA biomarkers for posttraumatic stress disorder and methods of use thereof
Inventors
Pollard, Harvey B. • Biswas, Roopa
Assignees
Uniformed Services University of Health Sciences • Henry M Jackson Foundation for Advancedment of Military Medicine Inc
Publication Number
US-10358679-B2
Publication Date
2019-07-23
Expiration Date
2035-09-25
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Abstract
Methods of detecting or diagnosing posttraumatic stress disorder (PTSD) in a human subject are disclosed. In addition, methods of monitoring the progression of PTSD in a human subject, methods of treating a patient with PTSD, kits for diagnosing PTSD in a human subject suspected of having PTSD, and methods of detecting a microRA (miRNA) or plurality of miRNAs in a biological sample from a human subject are also disclosed.
Core Innovation
The invention relates to methods of detecting or diagnosing posttraumatic stress disorder (PTSD) in a human subject by determining levels of one or more specific microRNAs (miRNAs) in a biological sample and comparing these levels against those from subjects not suffering from PTSD, where an increase or decrease in miRNA levels indicates the possibility of PTSD. It also includes methods of monitoring PTSD progression by analyzing miRNA levels at multiple time points, calculating ratios of miRNA levels, and methods for treating PTSD based on miRNA detection.
PTSD is a psychiatric disorder occurring after traumatic events, characterized by hyperarousal, avoidance behavior, and mental re-experiencing of trauma. The diagnosis is primarily clinical and lacks objective biomarkers. There is evidence of genetic risk factors and brain functional changes in PTSD, but the correlation with molecular markers is not fully understood. The invention aims to provide molecular biomarkers, specifically miRNAs, that serve as diagnostic and prognostic tools for PTSD.
The disclosed methods utilize specific miRNAs identified to have significantly altered levels in PTSD patients compared to controls. These miRNAs, measured in biological samples such as plasma or cerebrospinal fluid, can be detected and quantified using methods like real-time PCR. The invention also encompasses kits comprising polynucleotide molecules to detect PTSD-related miRNAs and methods to administer treatments including SSRIs, cognitive behavior therapy, or miRNA mimics/inhibitors based on the diagnostic results.
Claims Coverage
The patent contains one independent claim focused on a method of detecting specific microRNAs in a biological sample from a human subject suspected of having PTSD.
Method of detecting specific microRNA levels for PTSD diagnosis
A method comprising obtaining a biological sample from a human suspected of PTSD and measuring the levels of miR-142-3p, miR-181a, and miR-20a in the sample to detect miRNA associated with PTSD.
The claims cover a method centered on measuring levels of specific miRNAs in biological samples from individuals suspected of PTSD, particularly focusing on miR-142-3p, miR-181a, and miR-20a, to support diagnosis of the disorder.
Stated Advantages
The ratio of specific miRNAs extends the dynamic range and increases the statistical significance of PTSD diagnosis, reducing false positives and negatives.
miRNAs are stable in serum, making them reliable biomarkers resistant to degradation and storage conditions.
Certain miRNAs provide insights into different aspects of PTSD including risk, progression, response to treatment, and recovery.
Documented Applications
Detecting or diagnosing PTSD in human subjects by quantifying specific miRNAs in plasma or cerebrospinal fluid samples collected at defined times (e.g., 2 AM, 9 AM).
Monitoring the progression of PTSD in patients by assessing changes in miRNA levels over time from sequential biological samples.
Using miRNA biomarker levels to guide therapeutic choices including administration of SSRIs, cognitive behavior therapy, miRNA mimics, or inhibitors.
Diagnostic kits comprising polynucleotide molecules that hybridize to PTSD-related miRNAs for use in detecting the presence of PTSD in suspected subjects.
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