Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-18T06:36:34.221Z Has data issue: false hasContentIssue false

HOMA-IR increase after antidepressant treatment in depressed patients with the Met allele of the Val66Met BDNF genetic polymorphism

Published online by Cambridge University Press:  11 December 2018

Séverine Martin
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France
Romain Colle*
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France
Khalil El Asmar
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France
Adrien Rigal
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France
Albane Vievard
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France
Bruno Feve
Affiliation:
Service d'endocrinologie, Hôpital Saint-Antoine, Assistance Publique Hôpitaux de Paris, Paris, France Sorbonne Université, INSERM UMR S_938, Centre de Recherche Saint-Antoine, Paris, France
Laurent Becquemont
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France Centre de Recherche Clinique Paris Sud, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France
Céline Verstuyft
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Centre de Recherche Clinique Paris Sud, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France Centre de Ressources Biologiques Paris Sud, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, France
Emmanuelle Corruble
Affiliation:
INSERM UMR-1178, CESP, Equipe “Dépression et Antidépresseurs”, Université Paris-Sud, Faculté de Médecine Paris-Sud, Le Kremlin Bicêtre, F-94276, France Service Hospitalo-Universitaire de Psychiatrie, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Le Kremlin Bicêtre, F-94275, France
*
Author for correspondence: Romain Colle, E-mail: [email protected]

Abstract

Background

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with response to antidepressant drugs in depressed patients and with metabolic side effects after antipsychotic treatment. This study aims to assess the association between this polymorphism and insulin resistance after antidepressant treatment in depressed patients.

Methods

One hundred forty-eight Caucasian patients with a current unipolar major depressive episode (DSM IV-TR) were genotyped for the BDNF Val66Met polymorphism and assessed at baseline and after 3 and 6 months of antidepressant treatment for the ‘Homoeostasis model assessment of insulin resistance’ (HOMA-IR) index, a valid measure of insulin resistance based on fasting plasma insulinaemia and glycaemia. Because validity assumptions were fulfilled, data were analysed using analysis of variance for repeated measures.

Results

The 52 (35%) Met carriers and 96 (65%) Val/Val patients were not different at baseline for clinical characteristics and HOMA-IR. A significant Val66Met × time interaction (p = 0.02), a significant time effect (p = 0.03) and a significant Val66Met effect (p = 0.0497) were shown for HOMA-IR. A significant Val66Met × time interaction (p = 0.01) and a significant time effect (p = 0.003) were shown for fasting glycaemia. HOMA-IR and fasting glycaemia changes after antidepressant treatment were significantly higher in Met carrier than in Val/Val patients (HOMA-IR changes: Met: 0.71 ± 3.29 v. Val/Val: −0.16 ± 1.34, t = 2.3, df = 146, p = 0.02, glycaemia changes: Met: 0.09 ± 0.30 v. Val/Val: 0.02 ± 0.16, t = −2.0, df = 146, p = 0.045).

Conclusions

The Met allele of the Val66Met BDNF polymorphism confers to depressed patients a higher risk of insulin-resistance after antidepressant treatment. These patients could benefit from specific monitoring of metabolism and preventive measures.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

These authors contributed equally to this work.

References

Alberti, KG, Zimmet, P, Shaw, J and Group, IDFETFC (2005). The metabolic syndrome – a new worldwide definition. Lancet 366, 10591062.Google Scholar
Castren, E and Rantamaki, T (2010). The role of BDNF and its receptors in depression and antidepressant drug action: reactivation of developmental plasticity. Developmental Neurobiology 70, 289297.Google Scholar
Colle, R, Trabado, S, David, DJ, Brailly-Tabard, S, Hardy, P, Falissard, B, Feve, B, Becquemont, L, Verstuyft, C and Corruble, E (2017). Plasma BDNF level in major depression: biomarker of the Val66Met BDNF polymorphism and of the clinical course in met carrier patients. Neuropsychobiology 75, 3945.Google Scholar
Corruble, E, El Asmar, K, Trabado, S, Verstuyft, C, Falissard, B, Colle, R, Petit, AC, Gressier, F, Brailly-Tabard, S, Ferreri, F, Lépine, JP, Haffen, E, Polosan, M, Bourrier, C, Perlemuter, G, Chanson, P, Fève, B and Becquemont, L (2015) Treating major depressive episodes with antidepressants can induce or worsen metabolic syndrome: results of the METADAP cohort. World Psychiatry: Official Journal of the World Psychiatric Association 14, 366367.Google Scholar
Coulbault, L, Beaussier, M, Verstuyft, C, Weickmans, H, Dubert, L, Tregouet, D, Descot, C, Parc, Y, Lienhart, A, Jaillon, P and Becquemont, L (2006) Environmental and genetic factors associated with morphine response in the postoperative period. Clinical Pharmacology and Therapeutics 79, 316324.Google Scholar
Delahanty, LM, Pan, Q, Jablonski, KA, Watson, KE, McCaffery, JM, Shuldiner, A, Kahn, SE, Knowler, WC, Florez, JC and Franks, PW & Diabetes Prevention Program Research G (2012). Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the diabetes prevention program. Diabetes Care 35, 363366.Google Scholar
Duman, RS and Monteggia, LM (2006) A neurotrophic model for stress-related mood disorders. Biological Psychiatry 59, 11161127.Google Scholar
Egan, MF, Kojima, M, Callicott, JH, Goldberg, TE, Kolachana, BS, Bertolino, A, Zaitsev, E, Gold, B, Goldman, D, Dean, M, Lu, B and Weinberger, DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257269.Google Scholar
Eyileten, C, Kaplon-Cieslicka, A, Mirowska-Guzel, D, Malek, L and Postula, M (2017) Antidiabetic effect of brain-derived neurotrophic factor and Its association with inflammation in type 2 diabetes Mellitus. Journal of Diabetes Research 2017, 2823671.Google Scholar
Frodl, T, Schule, C, Schmitt, G, Born, C, Baghai, T, Zill, P, Bottlender, R, Rupprecht, R, Bondy, B, Reiser, M, Moller, HJ and Meisenzahl, EM (2007) Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression. Archives of General Psychiatry 64, 410416.Google Scholar
Global Burden of Disease Study C (2015) Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386, 743800.Google Scholar
Gunstad, J, Schofield, P, Paul, RH, Spitznagel, MB, Cohen, RA, Williams, LM, Kohn, M and Gordon, E (2006) BDNF val66met polymorphism is associated with body mass index in healthy adults. Neuropsychobiology 53, 153156.Google Scholar
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.Google Scholar
Hong, KW, Lim, JE, Go, MJ, Shin Cho, Y, Ahn, Y, Han, BG and Oh, B (2012). Recapitulation of the association of the Val66Met polymorphism of BDNF gene with BMI in Koreans. Obesity 20, 18711875.Google Scholar
Kernie, SG, Liebl, DJ and Parada, LF (2000) BDNF regulates eating behavior and locomotor activity in mice. The EMBO Journal 19, 12901300.Google Scholar
Laakso, M and Kuusisto, J (2014) Insulin resistance and hyperglycaemia in cardiovascular disease development. Nature Reviews. Endocrinology 10, 293302.Google Scholar
Lee, Y, Lim, SW, Kim, SY, Chung, JW, Kim, J, Myung, W, Song, J, Kim, S, Carroll, BJ and Kim, DK (2013) Association between the BDNF Val66Met polymorphism and chronicity of depression. Psychiatry Investigation 10, 5661.Google Scholar
Lee, JH, Park, SK, Ryoo, JH, Oh, CM, Mansur, RB, Alfonsi, JE, Cha, DS, Lee, Y, McIntyre, RS and Jung, JY (2017) The association between insulin resistance and depression in the Korean general population. Journal of Affective Disorders 208, 553559.Google Scholar
Liu, W, Han, X, Zhou, X, Zhang, S, Cai, X, Zhang, L, Li, Y, Li, M, Gong, S and Ji, L (2016) Brain derived neurotrophic factor in newly diagnosed diabetes and prediabetes. Molecular and Cellular Endocrinology 429, 106113.Google Scholar
Ma, XY, Qiu, WQ, Smith, CE, Parnell, LD, Jiang, ZY, Ordovas, JM, Tucker, KL and Lai, CQ (2012) Association between BDNF rs6265 and obesity in the Boston Puerto Rican Health Study. Journal of Obesity 2012, 102942.Google Scholar
Matthews, DR, Hosker, JP, Rudenski, AS, Naylor, BA, Treacher, DF and Turner, RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419.Google Scholar
Nakagawa, T, Tsuchida, A, Itakura, Y, Nonomura, T, Ono, M, Hirota, F, Inoue, T, Nakayama, C, Taiji, M and Noguchi, H (2000) Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes 49, 436444.Google Scholar
Nakagawa, T, Ono-Kishino, M, Sugaru, E, Yamanaka, M, Taiji, M and Noguchi, H (2002) Brain-derived neurotrophic factor (BDNF) regulates glucose and energy metabolism in diabetic mice. Diabetes/Metabolism Research and Reviews 18, 185191.Google Scholar
Nibuya, M, Morinobu, S and Duman, RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience 15, 75397547.Google Scholar
Nicholson, A, Kuper, H and Hemingway, H (2006) Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. European Heart Journal 27, 27632774.Google Scholar
Noble, EE, Billington, CJ, Kotz, CM and Wang, C (2011) The lighter side of BDNF. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 300, R1053R1069.Google Scholar
Ossola, P, Paglia, F, Pelosi, A, De Panfilis, C, Conte, G, Tonna, M, Ardissino, D and Marchesi, C (2015) Risk factors for incident depression in patients at first acute coronary syndrome. Psychiatry Research 228, 448453.Google Scholar
Penninx, BW (2017) Depression and cardiovascular disease: epidemiological evidence on their linking mechanisms. Neuroscience and Biobehavioral Reviews 74, 277286.Google Scholar
Penninx, BW, Milaneschi, Y, Lamers, F and Vogelzangs, N (2013) Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile. BMC Medicine 11, 129.Google Scholar
Rios, M, Fan, G, Fekete, C, Kelly, J, Bates, B, Kuehn, R, Lechan, RM and Jaenisch, R (2001). Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Molecular Endocrinology 15, 17481757.Google Scholar
Rush, AJ, Trivedi, MH, Ibrahim, HM, Carmody, TJ, Arnow, B, Klein, DN, Markowitz, JC, Ninan, PT, Kornstein, S, Manber, R, Thase, ME, Kocsis, JH and Keller, MB (2003) The 16-Item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry 54, 573583.Google Scholar
Serodio, KJ, Ardern, CI, Rotondi, MA and Kuk, JL (2014) Tricyclic and SSRI usage influences the association between BMI and health risk factors. Clinical Obesity 4, 296302.Google Scholar
Stewart, JW, McGrath, PJ, Quitkin, FM and Klein, DF (2007) Atypical depression: current status and relevance to melancholia. Acta Psychiatrica Scandinavica. Supplementum (433), 5871.Google Scholar
Takeuchi, F, Yamamoto, K, Katsuya, T, Nabika, T, Sugiyama, T, Fujioka, A, Isono, M, Ohnaka, K, Fujisawa, T, Nakashima, E, Ikegami, H, Nakamura, J, Yamori, Y, Yamaguchi, S, Kobayashi, S, Ogihara, T, Takayanagi, R and Kato, N (2011) Association of genetic variants for susceptibility to obesity with type 2 diabetes in Japanese individuals. Diabetologia 54, 13501359.Google Scholar
Thorleifsson, G, Walters, GB, Gudbjartsson, DF, Steinthorsdottir, V, Sulem, P, Helgadottir, A, Styrkarsdottir, U, Gretarsdottir, S, Thorlacius, S, Jonsdottir, I, Jonsdottir, T, Olafsdottir, EJ, Olafsdottir, GH, Jonsson, T, Jonsson, F, Borch-Johnsen, K, Hansen, T, Andersen, G, Jorgensen, T, Lauritzen, T, Aben, KK, Verbeek, AL, Roeleveld, N, Kampman, E, Yanek, LR, Becker, LC, Tryggvadottir, L, Rafnar, T, Becker, DM, Gulcher, J, Kiemeney, LA, Pedersen, O, Kong, A, Thorsteinsdottir, U and Stefansson, K (2009) Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nature Genetics 41, 1824.Google Scholar
Tsuchida, A, Nakagawa, T, Itakura, Y, Ichihara, J, Ogawa, W, Kasuga, M, Taiji, M and Noguchi, H (2001) The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice. Diabetologia 44, 555566.Google Scholar
Unger, TJ, Calderon, GA, Bradley, LC, Sena-Esteves, M and Rios, M (2007) Selective deletion of BDNF in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience 27, 1426514274.Google Scholar
Wu, L, Xi, B, Zhang, M, Shen, Y, Zhao, X, Cheng, H, Hou, D, Sun, D, Ott, J, Wang, X and Mi, J (2010) Associations of six single nucleotide polymorphisms in obesity-related genes with BMI and risk of obesity in Chinese children. Diabetes 59, 30853089.Google Scholar
Xi, B, Cheng, H, Shen, Y, Chandak, GR, Zhao, X, Hou, D, Wu, L, Wang, X and Mi, J (2013) Study of 11 BMI-associated loci identified in GWAS for associations with central obesity in the Chinese children. PLoS ONE 8, e56472.Google Scholar
Xu, B, Goulding, EH, Zang, K, Cepoi, D, Cone, RD, Jones, KR, Tecott, LH and Reichardt, LF (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nature Neuroscience 6, 736742.Google Scholar
Zhang, Y, Chen, M, Wu, Z, Chen, J, Yu, S, Fang, Y and Zhang, C (2013) Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results. PLoS ONE 8, e72652.Google Scholar