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The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice.

ABSTRACT: Although genetic variants may play a key role in development of treatment-resistant depression (TRD), relevant research is scarce.To examine whether the polymorphisms of BDNF (rs6265) and NTRK2 (rs1387923, rs2769605 and rs1565445) genes confer risk for TRD in major depressive disorder (MDD), a total of 948 MDD patients were recruited in a 12-week, multicenter, prospective longitudinal study.Our study showed a significant allelic association between rs1565445 and TRD with an excess of the T allele in the TRD group, compared to non-TRD group (OR = 1.43, 95%CI: 1.16-1.76, p = 0.0008); while patients with genotype C/C and T/C in rs1565445 were less likely to develop TRD than those carrying T/T (OR = 0.52, 95%CI: 0.33-0.82; OR = 0.72, 95%CI: 0.54-0.97, respectively; p = 0.005). Haplotype T-T (rs1565445 and rs1387923) had 1.41-fold increased risk of TRD (p = 0.0014). Furthermore, significant four-locus (rs1387923-rs1565445-rs2769605-rs6265) gene-gene interactions were detected by the Multifactor-dimensionality reduction (MDR) method.These results suggest that the interactions of BDNF (rs6265) with NTRK2 (rs1387923, rs2769605 and rs1565445) gene polymorphisms likely play an essential role in the development of TRD in Han Chinese MDD patients.

SUBMITTER: Li Z

PROVIDER: S-EPMC3584686 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice.

Li Zezhi Z Zhang Yanxia Y Wang Zuowei Z Chen Jun J Fan Jinbo J Guan Yangtai Y Zhang Chen C Yuan Chengmei C Hong Wu W Wang Yong Y Wu Zhiguo Z Huang Jia J Hu Yingyan Y Cao Lan L Yi Zhenghui Z Cui Donghong D Yu Shunying S Fang Yiru Y

Journal of psychiatric research 20121106 1

<h4>Background</h4>Although genetic variants may play a key role in development of treatment-resistant depression (TRD), relevant research is scarce.<h4>Methods</h4>To examine whether the polymorphisms of BDNF (rs6265) and NTRK2 (rs1387923, rs2769605 and rs1565445) genes confer risk for TRD in major depressive disorder (MDD), a total of 948 MDD patients were recruited in a 12-week, multicenter, prospective longitudinal study.<h4>Results</h4>Our study showed a significant allelic association betw ...[more]

PMID: 23137999

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Project description:The association between BDNF gene functional Val66Met polymorphism rs6265 and the schizophrenia is far from being consistent. In addition to the heterogeneous in schizophrenia per se leading to the inconsistent results, the interaction among multi-genes is probably playing the main role in the pathogenesis of schizophrenia, but not a single gene. Neurotrophic tyrosine kinase receptor 2 (NTRK2) is the high-affinity receptor of BDNF, and was reported to be associated with mood disorders, though no literature reported the association with schizophrenia. Thus, in the present study, total 402 patients with paranoid schizophrenia (the most common subtype of schizophrenia) and matched 406 healthy controls were recruited to investigate the role of rs6265 in BDNF, three polymorphisms in NTRK2 gene (rs1387923, rs2769605 and rs1565445) and their interaction in the susceptibility to paranoid schizophrenia in a Chinese Han population. We did not observe significant differences in allele and genotype frequencies between patients and healthy controls for all four polymorphisms separately. The haplotype analysis also showed no association between haplotype of NTRK2 genes (rs1387923, rs2769605, and rs1565445) and paranoid schizophrenia. However, we found the association between the interaction of BDNF and NTRK2 with paranoid schizophrenia by using the MDR method followed by conventional statistical analysis. The best gene-gene interaction model was a three-locus model (BDNF rs6265, NTRK2 rs1387923 and NTRK2 rs2769605), in which one low-risk and three high-risk four-locus genotype combinations were identified. Our findings implied that single polymorphism of rs6265 rs1387923, rs2769605, and rs1565445 in BDNF and NTRK2 were not associated with the development of paranoid schizophrenia in a Han population, however, the interaction of BDNF and NTRK2 genes polymorphisms (BDNF-rs6265, NTRK2-rs1387923 and NTRK2-rs2769605) may be involved in the susceptibility to paranoid schizophrenia.

Project description:BackgroundLongitudinal studies on functional outcome after colon resection are limited.ObjectiveExamine bowel dysfunction and related distress one and three years after colon resection utilizing the low anterior resection syndrome score as well as specific validated items.DesignThis study presents the long-term results of bowel dysfunction and related distress based on the quality of life in colon cancer study, an observational, prospective multicenter study of patients with newly diagnosed colon cancer.SettingsThe study was conducted at 21 Swedish and Danish surgical centers between 2015 and 2019.PatientsAll patients who underwent right- or left-sided colon resection were considered eligible. Exclusion criteria were age below 18, cognitive impairment or inability to understand Swedish/Danish. Patients completed extensive questionnaires at diagnosis, and after one and three years. Clinical data were supplemented by national quality registries.Main outcome measuresThe low anterior resection syndrome score, specific bowel symptoms and the patient-reported distress were assessed.ResultsOf 1,221 patients (83% response rate), 17% reported major LARS one year after either type of resection, consistent at 3 years (17% right, 16% left). In the long-term, the only significant difference between types of resection was a high occurrence of loose stools following right-sided resections. Overall, less than one-fifth of patients experienced distress, with women reporting more frequent symptoms and greater distress. In particular, incontinence and loose stools correlated strongly with distress.LimitationsAbsence of pre-diagnosis bowel function data.ConclusionsOur study indicates that bowel function remains largely intact following colon resection, with only a minority reporting significant distress. Adverse outcomes were more common among women. The occurrence of loose stools following right-sided resection and the association between incontinence, loose stools, and distress highlights a need for postoperative evaluations and more thorough assessments beyond the LARS score when evaluating colon cancer patients. See Video Abstract.

Dataset Information

The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice.

Publications

The role of BDNF, NTRK2 gene and their interaction in development of treatment-resistant depression: data from multicenter, prospective, longitudinal clinic practice.

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