Methods to identify patients at risk of developing adverse events during treatment with antidepressant medication

Abstract

The invention provides a method of screening patients to identify those patients more likely to exhibit an increased risk of treatment-emergent suicidal ideation comprising: (a) obtaining a sample of genetic material from the patients, and (b) assaying the sample for the presence of a genotype in the patients which is associated with an increased risk of treatment-emergent suicidal ideation, wherein the genotype is characterized by a polymorphism in a gene selected from the group consisting of glutamine receptor, ionotropic, kainate 2 (GRIK2); glutamate receptor ionotropic AMPA 3 (GRIA3); and combinations thereof.

1 . A method of screening patients to identify those patients more likely to exhibit an increased risk of treatment-emergent suicidal ideation comprising:
 (a) obtaining a sample of genetic material from the patients, and   (b) assaying the sample for the presence of a genotype in the patients which is associated with an increased risk of treatment-emergent suicidal ideation,   wherein the genotype is characterized by a polymorphism in a gene selected from the group consisting of glutamine receptor, ionotropic, kainate 2 (GRIK2); glutamate receptor ionotropic AMPA 3 (GRIA3); and combinations thereof.   
     
     
         2 . The method of  claim 1 , wherein assaying comprises detecting the polymorphism by allele specific hybridization, allele specific oligonucleotide ligation, primer extension, minisequencing, mass spectroscopy, heteroduplex analysis, single strand conformational polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), oligonucleotide microarray analysis, temperature gradient gel electrophoresis (TGGE), and combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the gene is GRIK2. 
     
     
         4 . The method of  claim 3 , wherein the polymorphism is within intron 1 of GRIK2. 
     
     
         5 . The method of  claim 4 , wherein intron 1 of GRIK2 comprises SEQ ID NO: 1. 
     
     
         6 . The method of  claim 1 , wherein the gene is GRIA3. 
     
     
         7 . The method of  claim 6 , wherein the polymorphism is within intron 3 of GRIA3. 
     
     
         8 . The method of  claim 7 , wherein intron 3 of GRIA3 comprises SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 13. 
     
     
         9 . The method of  claim 1 , further comprising assaying for the presence of a genotype in the patients which is associated with an increased risk of treatment-emergent suicidal ideation, wherein the genotype is characterized by a polymorphism in a gene selected from the group consisting of glutamate receptor, ionotropic, N-methyl D-aspartate (GRIN) 2A; neurotrophic tyrosine receptor kinase (NTRK) 2; 5-hydroxytryptamine (serotonin) receptor (HTR) 3B, GRIA1; papilin (PAPLN); interleukin 28 receptor alpha (IL28RA); and combinations thereof. 
     
     
         10 . The method of  claim 9 , wherein assaying for the presence of the genotype comprises detecting the presence of SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO 12, or combinations thereof. 
     
     
         11 . A method of screening patients to identify those patients more likely to exhibit an increased risk of treatment-emergent suicidal ideation comprising:
 (a) obtaining a sample of genetic material from the patients, and   (b) assaying the sample for the presence of a genotype in the patients which is associated with an increased risk of treatment-emergent suicidal ideation,   wherein the genotype is characterized by a polymorphism in a gene selected from the group consisting of glutamate receptor, ionotropic, N-methyl D-aspartate (GRIN) 2A; neurotrophic tyrosine receptor kinase (NTRK) 2; 5-hydroxytryptamine (serotonin) receptor (HTR) 3B, GRIA1; papilin (PAPLN); interleukin 28 receptor alpha (IL28RA); and combinations thereof.   
     
     
         12 . The method of  claim 11 , wherein assaying comprises detecting the polymorphism by allele specific hybridization, allele specific oligonucleotide ligation, primer extension, minisequencing, mass spectroscopy, heteroduplex analysis, single strand conformational polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), oligonucleotide microarray analysis, temperature gradient gel electrophoresis (TGGE), and combinations thereof. 
     
     
         13 . The method of  claim 11 , wherein the gene is GRIN2A. 
     
     
         14 . The method of  claim 13 , wherein the polymorphism is within intron 3 of GRIN2A. 
     
     
         15 . The method of  claim 11 , wherein the gene is NTRK2. 
     
     
         16 . The method of  claim 15 , wherein the polymorphism is within intron 14 of NTRK2. 
     
     
         17 . The method of  claim 11 , wherein the gene is HTR3B. 
     
     
         18 . The method of  claim 17 , wherein the polymorphism is within intron 6 of HTR3B. 
     
     
         19 . The method of  claim 11 , wherein the gene is GRIA1. 
     
     
         20 . The method of  claim 19 , wherein the polymorphism is within intron 5 of GRIA1. 
     
     
         21 . The method of  claim 11 , wherein the gene is PAPLN. 
     
     
         22 . The method of  claim 21 , wherein the polymorphism is within intron 13 of PAPLN. 
     
     
         23 . The method of  claim 11 , wherein the gene is IL28RA. 
     
     
         24 . The method of  claim 23 , wherein the polymorphism is within exon 7 of IL28RA. 
     
     
         25 . The method of  claim 23 , wherein the polymorphism is within intron 4 of IL28RA.