Brain-derived neurotrophic factor, but not body weight, correlated with a reduction in depression scale scores in men with metabolic syndrome: a prospective weight-reduction study

I-Te Lee, Chia-Po Fu, Wen-Jane Lee, Kae-Woei Liang, Shih-Yi Lin, Chu-Jen Wan, Wayne Huey-Herng Sheu, I-Te Lee, Chia-Po Fu, Wen-Jane Lee, Kae-Woei Liang, Shih-Yi Lin, Chu-Jen Wan, Wayne Huey-Herng Sheu

Abstract

Background: Obesity, a critical component of metabolic syndrome (MetS), is associated with depression. Deficiency of brain-derived neurotrophic factor (BDNF) is involved in the mechanism of depression. We hypothesized that weight reduction would improve depressive symptoms via increasing BDNF levels in obese men.

Methods: Male adults with obesity were enrolled in a weight-reduction program for twelve weeks. All subjects underwent daily caloric restriction and an exercise program which was regularly assessed in group classes. Fasting blood samples and Zung Self-Rating Depression Scale (Zung SDS) scores were collected for assessments before and after the study.

Results: A total of 36 subjects completed this program. The average reduction in body weight was 8.4 ± 5.1 kg (8.8 ± 5.1%, P < 0.001). Fasting serum BDNF significantly increased after the study (from 40.4 ± 7.8 to 46.9 ± 8.9 ng/ml, P < 0.001). However, the depression symptoms, as assessed by the Zung Self-Rating Depression Scale (Zung SDS), did not reduce significantly (P = 0.486). Divided into subgroups based on changes in BDNF, Zung SDS scores were significantly reduced in subjects with greater BDNF increase than in those with minor BDNF change (-3.9 ± 6.2 vs. 2.3 ± 6.7, P = 0.009). The increased percentage of BDNF was inversely correlated with the change in Zung SDS (r = -0.380, P = 0.022). Multivariate regression analysis showed that reduction in BDNF was independently associated with change in Zung SDS (95% confidence interval -0.315 to -0.052, P = 0.008).

Conclusion: Zung SDS only significantly improved in men with increased fasting BDNF levels after a lifestyle intervention.

Trial registration: (NCT01065753, ClinicalTrials.gov).

Figures

Figure 1
Figure 1
Relationship between the percentage changes in BDNF and changes in the Zung Self-Rating Depression Scale (Zung SDS) score; r = -0.380, P = 0.022.

References

    1. National Cholesterol Education Program. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) JAMA. 2001;285(19):2486–2497. doi: 10.1001/jama.285.19.2486.
    1. Sattar N, Gaw A, Scherbakova O, Ford I, O'Reilly DS, Haffner SM, Isles C, Macfarlane PW, Packard CJ, Cobbe SM. et al.Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003;108(4):414–419. doi: 10.1161/01.CIR.0000080897.52664.94.
    1. Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, Van Pelt RE, Wang H, Eckel RH. The metabolic syndrome. Endocrine reviews. 2008;29(7):777–822. doi: 10.1210/er.2008-0024.
    1. Zimmet P, Magliano D, Matsuzawa Y, Alberti G, Shaw J. The metabolic syndrome: a global public health problem and a new definition. J Atherosclerosis Thromb. 2005;12(6):295–300. doi: 10.5551/jat.12.295.
    1. Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006;444(7121):881–887. doi: 10.1038/nature05488.
    1. Lee IT, Lee WJ, Huang CN. WHHS. The association of low-grade inflammation, urinary albumin, and insulin resistance with metabolic syndrome in nondiabetic Taiwanese. Metabolism. 2007;56(12):1708–1713. doi: 10.1016/j.metabol.2007.07.015.
    1. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M. et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New Engl J Med. 2001;344(18):1343–1350. doi: 10.1056/NEJM200105033441801.
    1. Ashley FW Jr, Kannel WB. Relation of weight change to changes in atherogenic traits: the Framingham Study. J Chron Dis. 1974;27(3):103–114. doi: 10.1016/0021-9681(74)90079-4.
    1. Brown T, Avenell A, Edmunds LD, Moore H, Whittaker V, Avery L, Summerbell C. Systematic review of long-term lifestyle interventions to prevent weight gain and morbidity in adults. Obes Rev. 2009;10(6):627–638. doi: 10.1111/j.1467-789X.2009.00641.x.
    1. Melville CA, Hamilton S, Hankey CR, Miller S, Boyle S. The prevalence and determinants of obesity in adults with intellectual disabilities. Obes Rev. 2007;8(3):223–230. doi: 10.1111/j.1467-789X.2006.00296.x.
    1. Jagust W, Harvey D, Mungas D, Haan M. Central obesity and the aging brain. Arch Neurol. 2005;62(10):1545–1548.
    1. Yaffe K. Metabolic syndrome and cognitive decline. Curr Alzheimer Res. 2007;4(2):123–126. doi: 10.2174/156720507780362191.
    1. Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA, Newman AB. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004;292(18):2237–2242. doi: 10.1001/jama.292.18.2237.
    1. Noble JM, Manly JJ, Schupf N, Tang MX, Mayeux R, Luchsinger JA. Association of C-reactive protein with cognitive impairment. Arch Neurol. 2010;67(1):87–92.
    1. Benoit SC, Clegg DJ, Seeley RJ, Woods SC. Insulin and leptin as adiposity signals. Recent Progr Horm Res. 2004;59:267–285. doi: 10.1210/rp.59.1.267.
    1. Luchsinger JA, Mayeux R. Adiposity and Alzheimer's disease. Curr Alzheimer Res. 2007;4(2):127–134. doi: 10.2174/156720507780362100.
    1. Milionis HJ, Florentin M, Giannopoulos S. Metabolic syndrome and Alzheimer's disease: a link to a vascular hypothesis? CNS spectrums. 2008;13(7):606–613.
    1. Lebrun B, Bariohay B, Moyse E, Jean A. Brain-derived neurotrophic factor (BDNF) and food intake regulation: a minireview. (Auton Neurosci: basic & clinical. 2006;126–127:30–38.
    1. Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA. Molecular cloning and expression of brain-derived neurotrophic factor. Nature. 1989;341(6238):149–152. doi: 10.1038/341149a0.
    1. Rosenfeld RD, Zeni L, Haniu M, Talvenheimo J, Radka SF, Bennett L, Miller JA, Welcher AA. Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif. 1995;6(4):465–471. doi: 10.1006/prep.1995.1062.
    1. Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ. Transport of brain-derived neurotrophic factor across the blood-brain barrier. Neuropharmacology. 1998;37(12):1553–1561. doi: 10.1016/S0028-3908(98)00141-5.
    1. Yamada K, Mizuno M, Nabeshima T. Role for brain-derived neurotrophic factor in learning and memory. Life Sciences. 2002;70(7):735–744. doi: 10.1016/S0024-3205(01)01461-8.
    1. Fernandes BS, Gama CS, Kauer-Sant'Anna M, Lobato MI, Belmonte-de-Abreu P, Kapczinski F. Serum brain-derived neurotrophic factor in bipolar and unipolar depression: a potential adjunctive tool for differential diagnosis. (J Psychiatr Res. 2009;43(15):1200–1204. doi: 10.1016/j.jpsychires.2009.04.010.
    1. Brunoni AR, Lopes M, Fregni F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008;11(8):1169–1180. doi: 10.1017/S1461145708009309.
    1. Toriya M, Maekawa F, Maejima Y, Onaka T, Fujiwara K, Nakagawa T, Nakata M, Yada T. Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus. J Neuroendocrinol. 2010;22(9):987–995. doi: 10.1111/j.1365-2826.2010.02039.x.
    1. Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes. 2000;49(3):436–444. doi: 10.2337/diabetes.49.3.436.
    1. Suwa M, Kishimoto H, Nofuji Y, Nakano H, Sasaki H, Radak Z, Kumagai S. Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus. Metabol Clin Exp. 2006;55(7):852–857. doi: 10.1016/j.metabol.2006.02.012.
    1. Golden E, Emiliano A, Maudsley S, Windham BG, Carlson OD, Egan JM, Driscoll I, Ferrucci L, Martin B, Mattson MP. Circulating brain-derived neurotrophic factor and indices of metabolic and cardiovascular health: data from the Baltimore Longitudinal Study of Aging. PLos One. 2010;5(4):e10099. doi: 10.1371/journal.pone.0010099.
    1. Levinger I, Goodman C, Matthews V, Hare DL, Jerums G, Garnham A, Selig S. BDNF, metabolic risk factors, and resistance training in middle-aged individuals. Med Sci Sports Exerc. 2008;40(3):535–541.
    1. Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, Fischer CP, Lindegaard B, Petersen AM, Taudorf S. et al.Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007;50(2):431–438. doi: 10.1007/s00125-006-0537-4.
    1. Chaldakov GN, Fiore M, Stankulov IS, Hristova M, Antonelli A, Manni L, Ghenev PI, Angelucci F, Aloe L. NGF, BDNF, leptin, and mast cells in human coronary atherosclerosis and metabolic syndrome. Arch Physiol Biochem. 2001;109(4):357–360. doi: 10.1076/apab.109.4.357.4249.
    1. Martin B, Pearson M, Kebejian L, Golden E, Keselman A, Bender M, Carlson O, Egan J, Ladenheim B, Cadet JL. et al.Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess. Endocrinology. 2007;148(9):4318–4333. doi: 10.1210/en.2007-0161.
    1. Zung WW. A Self-Rating Depression Scale. Arch Gen Psychiatr. 1965;12:63–70. doi: 10.1001/archpsyc.1965.01720310065008.
    1. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–419. doi: 10.1007/BF00280883.
    1. Lee IT, Lee WJ, Tsai IC, Liang KW, Lin SY, Wan CJ, Fu CP, Sheu WH. Brain-derived neurotrophic factor not associated with metabolic syndrome but inversely correlated with vascular cell adhesion molecule-1 in men without diabetes. Clin Chim Acta. 2012;413(9-10):944–948. doi: 10.1016/j.cca.2012.02.013.
    1. Pedersen BK, Pedersen M, Krabbe KS, Bruunsgaard H, Matthews VB, Febbraio MA. Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals. Exp Physiol. 2009;94(12):1153–1160. doi: 10.1113/expphysiol.2009.048561.
    1. Zoladz JA, Pilc A, Majerczak J, Grandys M, Zapart-Bukowska J, Duda K. Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men. J Physiol Pharmacol. 2008;59(Suppl 7):119–132.
    1. Pereira DS, de Queiroz BZ, Miranda AS, Rocha NP, Felicio DC, Mateo EC, Favero M, Coelho FM, Jesus-Moraleida F, Gomes Pereira DA. et al.Effects of physical exercise on plasma levels of brain-derived neurotrophic factor and depressive symptoms in elderly women–a randomized clinical trial. Arch Phys Med Rehabil. 2013;94(8):1443–1450. doi: 10.1016/j.apmr.2013.03.029.
    1. Schmidt-Kassow M, Schadle S, Otterbein S, Thiel C, Doehring A, Lotsch J, Kaiser J. Kinetics of serum brain-derived neurotrophic factor following low-intensity versus high-intensity exercise in men and women. Neuroreport. 2012;23(15):889–893. doi: 10.1097/WNR.0b013e32835946ca.
    1. Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA. et al.Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010;67(1):71–79.
    1. Kuo FC, Lee CH, Hsieh CH, Kuo P, Chen YC, Hung YJ. Lifestyle modification and behavior therapy effectively reduce body weight and increase serum level of brain-derived neurotrophic factor in obese non-diabetic patients with schizophrenia. Psychiatr Res. 2013;209(2):150–154. doi: 10.1016/j.psychres.2012.11.020.
    1. Zai GC, Zai CC, Chowdhury NI, Tiwari AK, Souza RP, Lieberman JA, Meltzer HY, Potkin SG, Muller DJ, Kennedy JL. The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain. Progr Neuro Psychopharmacol Biol Psychiatr. 2012;39(1):96–101. doi: 10.1016/j.pnpbp.2012.05.014.
    1. Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H. Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol. 2009;94(10):1062–1069. doi: 10.1113/expphysiol.2009.048512.
    1. Martinowich K, Manji H, Lu B. New insights into BDNF function in depression and anxiety. Nat Neurosci. 2007;10(9):1089–1093. doi: 10.1038/nn1971.
    1. Chaput JP, Drapeau V, Hetherington M, Lemieux S, Provencher V, Tremblay A. Psychobiological effects observed in obese men experiencing body weight loss plateau. Depress Anxiety. 2007;24(7):518–521. doi: 10.1002/da.20264.
    1. Kamezaki F, Sonoda S, Nakata S, Okazaki M, Tamura M, Abe H, Takeuchi M, Otsuji Y. Elevated depressive symptoms are associated with hypertriglyceridemia in Japanese male workers. Intern Med. 2011;50(21):2485–2490. doi: 10.2169/internalmedicine.50.5667.
    1. Chaput JP, Drapeau V, Hetherington M, Lemieux S, Provencher V, Tremblay A. Psychobiological impact of a progressive weight loss program in obese men. Physiol Behav. 2005;86(1–2):224–232.
    1. Pagoto S, Bodenlos JS, Kantor L, Gitkind M, Curtin C, Ma Y. Association of major depression and binge eating disorder with weight loss in a clinical setting. Obesity. 2007;15(11):2557–2559. doi: 10.1038/oby.2007.307.
    1. Ludman E, Simon GE, Ichikawa LE, Operskalski BH, Arterburn D, Linde JA, Jeffery RW, Rohde P, Finch EA. Does depression reduce the effectiveness of behavioral weight loss treatment? Behav Med. 2010;35(4):126–134.
    1. Faulconbridge LF, Wadden TA, Rubin RR, Wing RR, Walkup MP, Fabricatore AN, Coday M, Van Dorsten B, Mount DL, Ewing LJ. et al.One-year changes in symptoms of depression and weight in overweight/obese individuals with type 2 diabetes in the Look AHEAD study. Obesity. 2012;20(4):783–793. doi: 10.1038/oby.2011.315.
    1. Karczewska-Kupczewska M, Straczkowski M, Adamska A, Nikolajuk A, Otziomek E, Gorska M, Kowalska I. Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity. Clin Biochem. 2011;44(10–11):817–820.
    1. Lechin F, van der Dijs B. Central nervous system circuitry involved in the hyperinsulinism syndrome. Neuroendocrinology. 2006;84(4):222–234. doi: 10.1159/000098005.
    1. Kleinridders A, Konner AC, Bruning JC. CNS-targets in control of energy and glucose homeostasis. Curr Opin Pharmacol. 2009;9(6):794–804. doi: 10.1016/j.coph.2009.10.006.
    1. Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, Nakazato M, Watanabe H, Shinoda N, Okada S. et al.Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatr. 2003;54(1):70–75. doi: 10.1016/S0006-3223(03)00181-1.
    1. Redmon JB, Bertoni AG, Connelly S, Feeney PA, Glasser SP, Glick H, Greenway F, Hesson LA, Lawlor MS, Montez M. et al.Effect of the look AHEAD study intervention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes. Diabetes Care. 2010;33(6):1153–1158. doi: 10.2337/dc09-2090.
    1. Rubin RR, Peyrot M, Gaussoin SA, Espeland MA, Williamson D, Faulconbridge LF, Wadden TA, Ewing L, Safford M, Evans-Hudnall G. et al.Four-year analysis of cardiovascular disease risk factors, depression symptoms, and antidepressant medicine use in the Look AHEAD (Action for Health in Diabetes) clinical trial of weight loss in diabetes. Diabetes Care. 2013;36(5):1088–1094. doi: 10.2337/dc12-1871.
    1. Look ARG, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM. et al.Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New Engl J Med. 2013;369(2):145–154.
    1. Karczewska-Kupczewska M, Kowalska I, Nikolajuk A, Adamska A, Zielinska M, Kaminska N, Otziomek E, Gorska M, Straczkowski M. Circulating brain-derived neurotrophic factor concentration is downregulated by intralipid/heparin infusion or high-fat meal in young healthy male subjects. Diabetes Care. 2012;35(2):358–362. doi: 10.2337/dc11-1295.
    1. Pillai A, Bruno D, Sarreal AS, Hernando RT, Saint-Louis LA, Nierenberg J, Ginsberg SD, Pomara N, Mehta PD, Zetterberg H. et al.Plasma BDNF levels vary in relation to body weight in females. PloS One. 2012;7(7):e39358. doi: 10.1371/journal.pone.0039358.
    1. Hashimoto K, Shimizu E, Iyo M. Critical role of brain-derived neurotrophic factor in mood disorders. Brain Res Rev. 2004;45(2):104–114. doi: 10.1016/j.brainresrev.2004.02.003.
    1. Hashimoto K. Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions. Psychiatr Clin Neurosci. 2010;64(4):341–357. doi: 10.1111/j.1440-1819.2010.02113.x.
    1. Krabbe KS, Mortensen EL, Avlund K, Pedersen AN, Pedersen BK, Jorgensen T, Bruunsgaard H. Brain-derived neurotrophic factor predicts mortality risk in older women. J Am Geriatr Soc. 2009;57(8):1447–1452. doi: 10.1111/j.1532-5415.2009.02345.x.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner