RATIONALE: In clinical practice, ketamine, an antagonist of the N-methyl-D-aspartate receptor (NMDAR), is used to alleviate depressive symptoms in patients with major depressive disorder (MDD), especially in those with treatment-resistant depression (TRD). Accordingly, the human gene coding for the 2B subunit of the NMDAR (GRIN2B) is considered a promising candidate gene for MDD susceptibility. OBJECTIVES: The primary aim of this study is to examine whether potentially functional polymorphisms of GRIN2B confer risk for MDD, and second to investigate whether GRIN2B acts as a genetic predictor for TRD in MDD patients. METHODS: We enrolled 178 TRD and 612 non-TRD patients as well as 779 healthy controls. RESULTS: Four potentially functional polymorphisms (rs1805502, rs890, rs1806201, and rs7301328) within GRIN2B were genotyped in all participants. The haplotype analysis found significant differences in the distribution of the G-T haplotype between the TRD and control groups (corrected P = 0.007), and the frequency of the G-T haplotype in TRD group was significantly higher than that in the controls (TRD/control ratio 0.31:0.21). Statistically significant differences in allele and genotype frequencies were detected between TRD and non-TRD groups for the rs1805502 polymorphism within GRIN2B. There was a significant allelic association between rs1805502 and TRD with an excess of the G allele in the TRD group, compared to non-TRD group (OR = 1.55, 95 % CI = 1.18-2.05, corrected P = 0.008). CONCLUSIONS: These initial findings strengthen the hypothesis that GRIN2B not only confers susceptibility to TRD, but also plays a genetic predictor for TRD in MDD patients.
RATIONALE: In clinical practice, ketamine, an antagonist of the N-methyl-D-aspartate receptor (NMDAR), is used to alleviate depressive symptoms in patients with major depressive disorder (MDD), especially in those with treatment-resistant depression (TRD). Accordingly, the human gene coding for the 2B subunit of the NMDAR (GRIN2B) is considered a promising candidate gene for MDD susceptibility. OBJECTIVES: The primary aim of this study is to examine whether potentially functional polymorphisms of GRIN2B confer risk for MDD, and second to investigate whether GRIN2B acts as a genetic predictor for TRD in MDDpatients. METHODS: We enrolled 178 TRD and 612 non-TRD patients as well as 779 healthy controls. RESULTS: Four potentially functional polymorphisms (rs1805502, rs890, rs1806201, and rs7301328) within GRIN2B were genotyped in all participants. The haplotype analysis found significant differences in the distribution of the G-T haplotype between the TRD and control groups (corrected P = 0.007), and the frequency of the G-T haplotype in TRD group was significantly higher than that in the controls (TRD/control ratio 0.31:0.21). Statistically significant differences in allele and genotype frequencies were detected between TRD and non-TRD groups for the rs1805502 polymorphism within GRIN2B. There was a significant allelic association between rs1805502 and TRD with an excess of the G allele in the TRD group, compared to non-TRD group (OR = 1.55, 95 % CI = 1.18-2.05, corrected P = 0.008). CONCLUSIONS: These initial findings strengthen the hypothesis that GRIN2B not only confers susceptibility to TRD, but also plays a genetic predictor for TRD in MDDpatients.
Authors: A John Rush; Madhukar H Trivedi; Stephen R Wisniewski; Andrew A Nierenberg; Jonathan W Stewart; Diane Warden; George Niederehe; Michael E Thase; Philip W Lavori; Barry D Lebowitz; Patrick J McGrath; Jerrold F Rosenbaum; Harold A Sackeim; David J Kupfer; James Luther; Maurizio Fava Journal: Am J Psychiatry Date: 2006-11 Impact factor: 18.112
Authors: Sheldon H Preskorn; Bryan Baker; Sheela Kolluri; Frank S Menniti; Michael Krams; Jaren W Landen Journal: J Clin Psychopharmacol Date: 2008-12 Impact factor: 3.153
Authors: Chadi G Abdallah; Christopher L Averill; Ramiro Salas; Lynnette A Averill; Philip R Baldwin; John H Krystal; Sanjay J Mathew; Daniel H Mathalon Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2017-10
Authors: Chadi G Abdallah; Andrea Jackowski; João R Sato; Xiangling Mao; Guoxin Kang; Raminder Cheema; Jeremy D Coplan; Sanjay J Mathew; Dikoma C Shungu Journal: Eur Neuropsychopharmacol Date: 2015-05-05 Impact factor: 4.600
Authors: Chadi G Abdallah; Jonas Hannestad; Graeme F Mason; Sophie E Holmes; Nicole DellaGioia; Gerard Sanacora; Lihong Jiang; David Matuskey; Ritvij Satodiya; Fabrizio Gasparini; Xin Lin; Jonathan Javitch; Beata Planeta; Nabeel Nabulsi; Richard E Carson; Irina Esterlis Journal: Biol Psychiatry Cogn Neurosci Neuroimaging Date: 2017-04-06