Assays and methods for selecting a treatment regimen for a subject with depression
View Patent ↗Disclosed herein are novel assays, systems and kits for selecting a treatment regimen for a subject with depression by identifying at least one nucleic acid polymorphism, e.g., but not limited to, at the MTHFR, MTR, or MTRR locus, and/or determining expression levels of peripheral biomarkers (e.g., SAM, SAH, and 4-HNE) in a test sample from a human subject. These biomarkers can be used to determine the effectiveness of treating a depressed subject with a folate-containing compound (alone or as an adjunct to an antidepressant). Additionally, these biomarkers can be used to select an appropriate treatment regimen for subjects with treatment-resistant depression (e.g., resistant to at least one selective serotonin reuptake inhibitor). Methods and compositions for treating a subject with depression and/or determining or improving the effectiveness of an antidepressant drug taken by a subject are also provided herein.
1. A method for treating a human subject with depression, the method comprising:
assaying a biological sample from said human subject who has been diagnosed with depression, and detecting in the biological sample a combination of the following single nucleotide polymorphisms (SNPs):
(i) a SNP at position 677 of SEQ ID NO. 1 or position 27 of SEQ ID NO. 7 (rs1801133) comprising at least one thymine “T” allele, wherein the SEQ ID NO. 1 and SEQ ID NO. 7 are each independently a portion of a genomic nucleic acid sequence of methylenetetrahydrofolate reductase (MTIWR); and
(ii) a SNP at position 2756 of SEQ ID NO. 2 or position 27 of SEQ ID NO. 9 (rs1805087) comprising at least one guanine “G” allele, wherein the SEQ ID NO. 2 and SEQ ID NO. 9 are each independently a portion of a genomic nucleic acid sequence of methionine synthase (MTR), which human subject has an increased likelihood of response to a treatment;
administering said treatment comprising a composition comprising an effective amount of a folate-containing compound, wherein said folate containing compound is at least 15 mg/day of 6-(S) 5-methyltetrahydrofolate, together with an antidepressant drug, wherein the antidepressant drug is a selective serotonin reuptake inhibitor, to the human subject to treat depression.
2. The method of claim 1 , wherein the biological sample comprises a sample selected from a blood sample, a urine sample, a buccal sample, a saliva sample and a cerebrospinal fluid sample.
3. The method of claim 1 , Wherein the assaying comprises the step of amplifying the test sample with at least one set of primers flanking any one of the SNPs.
4. The method of claim 3 , wherein at least two sets of primers amplifying the SNPs are used in a multiplex amplification assay.
5. The method of claim 1 , wherein the anti-depressant drug, which is a selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine, citalopram, paroxetine, escitalopram, sertraline, and any combinations thereof.
6. The method of claim 1 , wherein the depression is major depressive disorder.
7. The method of claim 1 , wherein the effective amount oft folate-containing compound is 15 mg/day to about 50 mg/day.
8. The method of claim 1 , wherein the subject with depression is resistant to at least one antidepressant monotherapy.