Microrna biomarkers for posttraumatic stress disorder and methods of use thereof
AssigneeThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
InventorsHarvey B. Pollard, Roopa Biswas
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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.
Claims36
A method of detecting or diagnosing post traumatic stress disorder (PTSD) in a human subject, the method comprising
- (a) determining levels of one or more micro RNA (miRNA) in a biological sample taken from the human subject, and
- (b) comparing the determined levels of the one or more miRNA against levels of the same one or more miRNA from human subjects determined not to be suffering from PTSD,
- wherein the one or more miRNA is selected from the group consisting of miR-142-3p, miR-518e, miR-181a, miR-20a, miR-672, miR-29a, miR-130a, miR-29c, miR-220, miR-484, miR-433, miR-337-5p, miR-486-5p, and miR-518f-3p, and
- an increase or decrease in the levels of the one or more miRNA compared to levels of the one or more miRNA from human subjects determined not to be suffering from PTSD is indicative that the human subject may be suffering from PTSD.
A method of detecting or diagnosing post traumatic stress disorder (PTSD) in a human subject suspected of having PTSD, the method comprising
- (a) quantifying levels of expression of one or more micro RNA (miRNA) in a first sample derived from the human subject,
- (b) quantifying levels of expression of the same one or more miRNA in a second sample derived from a body fluid obtained from human subjects determined not to be suffering from PTSD,
- (c) comparing the quantified levels of expression the one or more miRNA from the first sample with the levels of expression from the second sample,
- wherein detecting or diagnosing PTSD is achieved when there is increased or decreased levels of expression of the miRNA in the first sample compared with the second sample,
- the levels of expression are quantified by real-time PCR and the increased or decreased levels of expression are evaluated by having a p value of less than 0.05 in a statistical test;
- and
- the one or more miRNA is selected from the group consisting of miR-142-3p, miR-518e, miR-181a, miR-20a, miR-672, miR-29a, miR-130a, miR-29c, miR-220, miR-484, miR-433, miR-337-5p, miR-486-5p, and miR-518f-3p.
A method of monitoring the progression of post traumatic stress disorder (PTSD) in a human subject, the method comprising
- (a) analyzing at least two samples from the human subject with each sample taken at different time points to determine the levels of one or more specific micro RNA (miRNA), and
- (b) comparing the levels of the one or more specific miRNA, over time to determine if the human subject's levels of the one or more specific miRNA is changing over time,
- wherein the one or more miRNA is selected from the group consisting of miR-142-3p, miR-518e, miR-181a, miR-20a, miR-672, miR-29a, miR-130a, miR-29c, miR-220, miR-484, miR-433, miR-337-5p, miR-486-5p, and miR-518f-3p, and
- a change in the human subject's levels of the one or more specific miRNA over time is indicative that the human subject's risk of suffering from PTSD is increasing over time.
A method of detecting or diagnosing post traumatic stress disorder (PTSD) in a human subject, the method comprising
- (a) determining levels of a first micro RNA (miRNA) and a second miRNA in a biological sample taken from the human subject,
- (b) calculating the ratio of the determined levels of the first miRNA versus the second miRNA, and
- (c) comparing the calculated ratio for the sample from the human subject against ratio of the same first and second miRNA from human subjects determined not to be suffering from PTSD,
- wherein the one or more miRNA is selected from the group consisting of miR-142-3p, miR-518e, miR-181a, miR-20a, miR-672, miR-29a, miR-130a, miR-29c, miR-220, miR-484, miR-433, miR-337-5p, miR-486-5p, and miR-518f-3p, and
- an increase or decrease in the ratio for the sample from the human subject against ratio of the same first and second miRNA from human subjects determined not to be suffering from PTSD is indicative that the human subject may be suffering from PTSD.
The method of any preceding claim, wherein the biological sample is a plasma sample.
The method of any preceding claim, wherein the biological sample is a cerebrospinal fluid (CSF) sample.
The method of any preceding claim, wherein the human subject is male.
The method of any preceding claim, wherein the human subject is female.
The method of any preceding claim, wherein the human subject is at risk of suffering from PTSD.
The method of any preceding claim, wherein the levels of the miRNA are increased.
The method of any preceding claim, wherein the levels of the miRNA are decreased.
A kit for detecting or diagnosing post traumatic stress disorder (PTSD) in a human subject suspected of having PTSD, the kit comprising:
- one or more polynucleotide molecules that hybridize to one or more miRNAs selected from the group consisting of miR-142-3p, miR-518e, miR-181a, miR-20a, miR-672, miR-29a, miR-130a, miR-29c, miR-220, miR-484, miR-433, miR-337-5p, miR-486-5p, and miR-518f-3p;
- wherein the polynucleotide molecules are labeled or immobilized onto a solid substrate.
A method of detecting an miRNA or plurality of miRNAs in a biological sample, comprising:
- contacting a first biological sample from a subject suspected of having a PTSD with a probe for binding at least one miRNA selected from the group consisting of miR-142-3p, miR-518e, miR-181a, miR-20a, miR-672, miR-29a, miR-130a, miR-29c, miR-220, miR-484, miR-433, miR-337-5p, miR-486-5p, and miR-518f-3p, to produce an miRNA-probe complex;
- and
- detecting with Northern Blot Analysis or a real-time PCR the presence or absence of the miRNA-probe complex,
- wherein the absence of the miRNA-probe complex is indicative of the absence of the microRNA in the first biological sample.
Dependencies are inferred from the claim text.