期刊论文详细信息
Behavioral and Brain Functions
Functional Val66Met polymorphism of Brain-derived neurotrophic factor in type 2 diabetes with depression in Han Chinese subjects
Jian-Xin Zhou2  He-Chao Li2  Xue-Jun Bai1  Bao-Cheng Chang2  Chun-Jun Li2  Pei Sun2  Li-Ming Chen2 
[1] Center of Psychology and Behavior, Tianjin Normal University, Tianjin, China
[2] 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
关键词: Polymorphism;    Brain-derived neurotrophic factor (BDNF);    Depression;    Type 2 diabetes (T2DM);   
Others  :  793301
DOI  :  10.1186/1744-9081-9-34
 received in 2013-02-08, accepted in 2013-08-20,  发布年份 2013
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【 摘 要 】

Background

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of major depression. Individuals with type 2 diabetes (T2DM) have a high prevalence of major depression and low levels of BDNF. We therefore explored whether the BDNF Val66Met polymorphism is associated with co-morbid depression and whether depression affects the serum levels of BDNF in a Han Chinese subjects with T2DM.

Methods

A Total of 296 T2DM patients and 70 healthy volunteers (Health control, HC group) were recruited in this study. T2DM patients were divided into two subgroups: depressive diabetes group (DDM group, n = 64) and non-depressive diabetes group (NDDM group, n = 232), according to the presence or the absence of depression assessed by Center for Epidemiologic Studies Depression Scale (CES-D) and Patient Health Questionnaire-9 (PHQ-9). Val66Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). Serum BDNF levels were measured by ELISA kit.

Results

In this study, 21.6% (64/296) patients with T2DM had depression. The BDNF Val66Met genotype distributions were statistically different among the three groups (χ2 = 7.39, p < 0.05). DDM group carried the highest frequencies of Met allele (53.9%) compared to HC group (39.3%) and NDDM group (38.8%). Subjects with Met/Met had lowest serum BDNF levels (76.59 ± 5.12 pg/ml, F = 7.39, p < 0.05) compared to subjects with Val/Met (79.04 ± 5.19 pg/ml) and Val/Val (83.83 ± 3.97 pg/ml). Within T2DM group, it was also observed that the serum BDNF levels in DDM group were significantly lower than those in NDDM group (76.67 ± 5.35 vs. 79.84 ± 3.97 pg/ml, p < 0.05). In type 2 diabetes subjects, BDNF serum levels were significant correlations with genotypes (r = −0.346, p < 0.01), depression scores (r = −0.486, p < 0.01) and HbA1c (r = −0.168, p < 0.05). After adjustment for gender, HbA1c, BMI and numbers of complications, BDNF Val/Met genotype distributions (OR = 2.105, p < 0.05) and decreased serum BDNF levels (OR = 0.835, p < 0.01) were independently associated with depression in T2DM.

Conclusions

The BDNF Val66Met polymorphism might be implicated in the pathogenesis of depression in T2DM by decreasing serum BDNF levels in Han Chinese Subjects.

【 授权许可】

   
2013 Zhou et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Ali S, Stone MA, Peters JL, Davies MJ, Khunti K: The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis. Diabet Med 2006, 23:1165-73.
  • [2]Feinkohl I, Sattar N, Welsh P, Reynolds RM, Deary IJ: Association of N-Terminal Pro-Brain Natriuretic Peptide with Cognitive Function and Depression in Elderly People with Type 2 Diabetes. PLoS One 2012, 7:e44569.
  • [3]Egede LE, Nietert PJ, Zheng D: Depression and all-cause and coronary heart disease mortality among adults with and without diabetes. Diabetes Care 2005, 28:1339-45.
  • [4]Anderson RJ, Freedland KE, Clouse RE, Lustman PJ: The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001, 24:1069-78.
  • [5]Bogner HR, Morales KH, Post EP, Bruce ML: Diabetes, depression, and death: a randomized controlled trial of a depression treatment program for older adults based in primary care (PROSPECT). Diabetes Care 2007, 30:3005-10.
  • [6]Mattson MP, Maudsley S, Martin B: BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 2004, 27:589-94.
  • [7]Tsai SJ, Hong CJ, Liou YJ: Effects of BDNF polymorphisms on antidepressant action. Psychiatry Investig 2010, 7:236-42.
  • [8]Duman RS: Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromolecular Med 2004, 5(1):11-25.
  • [9]Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G: Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002, 109:143-8.
  • [10]Sen S, Duman R, Sanacora G: Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 2008, 64(6):527-532.
  • [11]Duman RS: Structural alterations in depression: cellular mechanisms underlying pathology and treatment of mood disorders. CNS Spectr 2002, 7:140-142.
  • [12]Ventriglia M, Bocchio Chiavetto L, Benussi L, Binetti G, Zanetti O: Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer's disease. Mol Psychiatry 2002, 7(2):136-7.
  • [13]Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS: The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 2003, 112:257-69.
  • [14]Molendijk ML, van Tol MJ, Penninx BW, van der Wee NJ, Aleman A, Veltman DJ: BDNF val66met affects hippocampal volume and emotion-related hippocampal memory activity. Transl Psychiatry 2012, 31(2):e74.
  • [15]Ribeiro L, Busnello JV, Cantor RM, Whelan F, Whittaker P: The brain-derived neurotrophic factor rs6265 (Val66Met) polymorphism and depression in Mexican-Americans. Neuroreport 2007, 18:1291-3.
  • [16]Jiang X, Xu K, Hoberman J, Tian F, Marko AJ: BDNF variation and mood disorders: a novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects. Neuropsychopharmacology 2005, 30(7):1353-61.
  • [17]Schumacher J, Jamra RA, Becker T, Ohlraun S, Klopp N: Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 2005, 58(4):307-314.
  • [18]Carrard A, Salzmann A, Perroud N, Gafner J, Malafosse A, Karege F: Genetic association of the Phosphoinositide-3 kinase in schizophrenia and bipolar disorder and interaction with a BDNF gene polymorphism. Brain Behav 2011, 1(2):119-24.
  • [19]Chen ZY, Jing D, Bath KG, Ieraci A, Khan T: Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior. Science 2006, 314:140-3.
  • [20]Tsai SJ, Hong CJ, Liou YJ: Effects of BDNF polymorphisms on antidepressant action. Psych Investig 2010, 7(4):236-42.
  • [21]Outhred T, Das P, Dobson-Stone C, Griffiths K, Felmingham KL, Bryant RA: The functional epistasis of 5-HTTLPR and BDNF Val66Met on emotion processing: a preliminary study. Brain Behav 2012, 2(6):778-88.
  • [22]Vasant DH, Payton A, Mistry S, Thompson DG, Hamdy S: The val66met polymorphism of brain-derived neurotrophic factor is associated with human esophageal hypersensitivity. Neurogastroenterol Motil 2013 Feb, 25(2):162-e85.
  • [23]Smolders R, Rijpkema M, Franke B, Fernández G: BDNF Val66Met polymorphism interacts with sex to influence bimanual motor control in healthy humans. Brain Behav 2012, 2(6):726-31.
  • [24]Hwang JP, Tsai SJ, Hong CJ, Yang CH, Lirng JF: The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression. Neurobiol Aging 2006, 27:1834-7.
  • [25]Hong CJ, Huo SJ, Yen FC, Tung CL, Pan GM, Tsai SJ: Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior. Neuropsychobiology 2003, 48:186-9.
  • [26]Arentoft A, Sweat V, Starr V, Oliver S, Hassenstab J: Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: evidence of a compensatory mechanism. Brain Cogn 2009, 71:147-52.
  • [27]Kernie SG, Liebl DJ, Parada LF: BDNF regulates eating behavior and locomotor activity in mice. EMBO J 2000, 19(6):1290-300.
  • [28]Fujinami A, Ohta K, Obayashi H, Fukui M, Hasegawa G, Nakamura N: Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance. Clin Biochem 2008, 41(10–11):812-7.
  • [29]Rao AA, Sridhar GR, Srinivas B, Das UN: Bioinformatics analysis of functional protein sequences reveals a role for brain-derived neurotrophic factor in obesity and type 2 diabetes mellitus. Med Hypotheses 2008, 70(2):424-9.
  • [30]Swift DL, Johannsen NM, Myers VH, Earnest CP, Smits JA: The effect of exercise training modality on serum brain derived neurotrophic factor levels in individuals with type 2 diabetes. PLoS One 2012, 7(8):e42785.
  • [31]Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P: Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia 2007, 50(2):431-8.
  • [32]Engum A: The role of depression and anxiety in onset of diabetes in a large population-based study. J Psychosom Res 2007, 62(1):31-8.
  • [33]Wang XD: Psychological assessment scale manual. Beijing: Chinese Mental Health Journal press; 1999:200-02.
  • [34]Zhang B, Fokkema M, Cuijpers P, Li J, Smits N, Beekman A: Measurement invariance of the Center for Epidemiological Studies Depression Scale (CES-D) among Chinese and Dutch elderly. BMC Med Res Methodol 2011, 11:74. BioMed Central Full Text
  • [35]Radlof LS: The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1977, 1:385-401.
  • [36]Chiu S, Webber MP, Zeig-Owens R, Gustave J, Lee R: Validation of the Center for Epidemiologic Studies Depression Scale in screening for major depressive disorder among retired firefighters exposed to the World Trade Center disaster. J Affect Disord 2010, 121:212-9.
  • [37]Huang FY, Chung H, Kroenke K, Delucchi KL, Spitzer RL: Using the Patient Health Questionnaire-9 to measure depression among racially and ethnically diverse primary care patients. J Gen Intern Med 2006, 21(6):547-52.
  • [38]Verhagen M, van der Meij A, van Deurzen PA, Janzing JG, Arias-Vásquez A, Buitelaar JK: Meta-analysis of the BDNF Val66Met polymorphism in major depressive disorder: effects of gender and ethnicity. Mol Psychiatry 2010, 15(3):260-71.
  • [39]Knol MJ, Heerdink ER, Egberts AC, Geerlings MI, Gorter KJ: Depressive symptoms in subjects with diagnosed and undiagnosed type 2 diabetes. Psychosom Med 2007, 69(4):300-5.
  • [40]Chen ZY, Ieraci A, Teng H, Dall H, Meng CX, Herrera DG: Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J Neurosci 2005, 25:156-6166.
  • [41]Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE: Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care 2000, 23(7):934-42.
  • [42]Liu Y, Maier M, Hao Y, Chen Y, Qin Y, Huo R: Factors related to quality of life for patients with type 2 diabetes with or without depressive symptoms - results from a community-based study in China. J Clin Nurs 2013, 22(1–2):80-8.
  • [43]Toalson P, Ahmed S, Hardy T, Kabinoff G: The Metabolic Syndrome in Patients With Severe Mental Illnesses. Prim Care Companion J Clin Psychiatry 2004, 6(4):152-158.
  • [44]Gonzalez JS, Safren SA, Cagliero E, Wexler DJ, Delahanty L: Depression, self-care, and medication adherence in type 2 diabetes: relationships across the full range of symptom severity. Diabetes Care 2007, 30(9):2222-7.
  • [45]Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG: Cross-national epidemiology of major depression and bipolar disorder. JAMA 1996, 276:293-299.
  • [46]Becker JB, Monteggia LM, Perrot-Sinal TS, Romeo RD, Taylor JR, Yehuda R: Stress and disease: is being female a predisposing factor? J Neurosci 2007, 27:11851-11855.
  • [47]Cahill L: Why sex matters for neuroscience. Nat Rev Neurosci 2006, 7:477-484.
  • [48]Abolfotouh MA, Daffallah AA, Khan MY, Khattab MS, Abdulmoneim I: Psychosocial assessment of geriatric subjects in Abha City. Saudi Arabia. East Mediterr Health J 2001, 7(3):481-91.
  • [49]Eisses AM, Kluiter H, Jongenelis K, Pot AM, Beekman AT, Ormel J: Risk indicators of depression in residential homes. Int J Geriatr Psychiatry 2004, 19(7):634-40.
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