Sex difference in the association of body mass index and BDNF levels in Chinese patients with chronic schizophrenia
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Rationale and objective
Schizophrenia displays sex differences in many aspects. Decreased brain-derived neurotrophic factor (BDNF) levels have been reported to be associated with high body weight or obesity as well as other psychopathological aspects in schizophrenia patients. This study aimed to explore sex differences in the relationship between serum BDNF levels and obesity in patients with chronic schizophrenia.
We recruited 132 Chinese patients with chronic schizophrenia (98 males and 34 females) and compared sex differences in the body mass index (BMI), obesity, serum BDNF levels, and their associations. Psychopathology symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). A regression model with various demographic and clinical variables was applied to predict the serum levels of BDNF.
Female patients had a higher rate of obesity and higher BMI, but lower BDNF levels than male schizophrenia patients. A significantly negative correlation was observed between BMI and BDNF levels only in female patients but not in male patients. The multiple regression model with demographic and clinical variables significantly predicted BDNF levels only in female patients, with a medium size effect. And only in female patients, BMI made a significant contribution to this prediction.
Our results indicate significant sex differences in the obesity, BMI, BDNF levels, and their association in chronic patients with schizophrenia, showing a significant inverse correlation between BMI and BDNF levels only in female patients. Thus, sex needs to be considered when assessing the relationship between BDNF and metabolic syndromes in schizophrenia.
KeywordsSchizophrenia Sex difference Brain-derived neurotrophic factor Obesity Body mass index
Funding for this study was provided by grants from the National Natural Science Foundation of China (81371477), Suzhou Key Medical Center for Psychiatric Diseases (Szzx201509), and Suzhou Key laboratory for Biological Psychiatry (SZS201722). These sources had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Compliance with ethical standards
The research protocol was approved by the Institutional Review Board, Beijing Hui-Long-Guan hospital (BHLGH). A psychiatrist explained the research protocol and procedures to the potential subject using language appropriate to the subject’s level of comprehension and emotional readiness. All subjects gave written informed consent to participate in the study.
Conflict of interest
The authors declare that they have no conflict of interest.
- Allison DB, Newcomer JW, Dunn AL, Blumenthal JA, Fabricatore AN, Daumit GL, Cope MB, Riley WT, Vreeland B, Hibbeln JR, Alpert JE (2009) Obesity among those with mental disorders. A National Institute of Mental Health Meeting Report. Am J Prev Med 36:341–350. https://doi.org/10.1016/j.amepre.2008.11.020 CrossRefGoogle Scholar
- Begliuomini S, Casarosa E, Pluchino N, Lenzi E, Centofanti M, Freschi L, Pieri M, Genazzani AD, Luisi S, Genazzani AR (2007) Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. Hum Reprod 22:995–1002. https://doi.org/10.1093/humrep/del479 CrossRefGoogle Scholar
- Bonaccorso S, Sodhi M, Li J, Bobo WV, Chen Y, Tumuklu M, Theleritis C, Jayathilake K, Meltzer HY (2015) The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with increased body mass index and insulin resistance measures in bipolar disorder and schizophrenia. Bipolar Disord 17:528–535. https://doi.org/10.1111/bdi.12294 CrossRefGoogle Scholar
- Chen H, Feng Y, Shu H, Lu TM, Zhu HM, Yang BL, Xiong M (2010) Survey on menopausal age and menstruation span in women in Pudong district of Shanghai (Article in Chinese). Zhonghua Fu Chan Ke Za Zhi 45:415–419Google Scholar
- Cohen, J., Cohen, P., West, S. G., Aiken LS (2003) Applied multiple regression/correlation analysis for the behavioral sciences (3rd ed.). Lawrence Erlbaum Associates., Mahwah, NJGoogle Scholar
- Eriksson J, Haring R, Grarup N, Vandenput L, Wallaschofski H, Lorentzen E, Hansen T, Mellström D, Pedersen O, Nauck M, Lorentzon M, Nystrup Husemoen LL, Völzke H, Karlsson M, Baumeister SE, Linneberg A, Ohlsson C (2017) Causal relationship between obesity and serum testosterone status in men: a bi-directional Mendelian randomization analysis. PLoS One 12:1–16. https://doi.org/10.1371/journal.pone.0176277 Google Scholar
- Fernandes BS, Steiner J, Berk M, Molendijk ML, Gonzalez-Pinto A, Turck CW, Nardin P, Gonçalves CA (2015) Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications. Mol Psychiatry 20:1108–1119. https://doi.org/10.1038/mp.2014.117 CrossRefGoogle Scholar
- Gray AH, Wright J, Bruce L, Oakley J (2015) Clinical pharmacy pocket companion, Second Edi. Pharmaceutical Press, LondonGoogle Scholar
- Green MJ, Matheson SL, Shepherd a Shepherd A, Weickert CS, Carr VJ (2011) Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 16:960–972. doi: https://doi.org/10.1038/mp.2010.88
- Kim S-W, Lee J-Y, Kang H-J, Kim SY, Bae KY, Kim JM, Shin IS, Yoon JS (2016) Gender-specific associations of the brain-derived neurotrophic factor Val66Met polymorphism with neurocognitive and clinical features in schizophrenia. Clin Psychopharmacol Neurosci 14:270–278. https://doi.org/10.9758/cpn.2016.14.3.270 CrossRefGoogle Scholar
- Kuo FC, Lee CH, Hsieh CH, Kuo P, Chen YC, Hung YJ (2013) 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. Psychiatry Res 209:150–154. https://doi.org/10.1016/j.psychres.2012.11.020 CrossRefGoogle Scholar
- Lee J (2012) A review of brain-derived neurotrophic factor as a candidate biomarker in schizophrenia. 10:61–70. https://doi.org/10.9758/cpn.2012.10.2.61
- Li J, Ye F, Xiao W, Tang X, Sha W, Zhang X, Wang J (2016a) Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia. Eur Psychiatry 36:23–28. https://doi.org/10.1016/j.eurpsy.2016.03.005 CrossRefGoogle Scholar
- Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC (2005) The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging 26:115–123. https://doi.org/10.1016/j.neurobiolaging.2004.03.002 CrossRefGoogle Scholar
- Luine V, Frankfurt M (2013) Interactions between estradiol, BDNF and dendritic spines in promoting memory. Neuroscience 239:34–45. https://doi.org/10.1016/j.neuroscience.2012.10.019 CrossRefGoogle Scholar
- Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, de Hert M (2013) Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders—a systematic review and meta-analysis. Schizophr Bull 39:306–318. https://doi.org/10.1093/schbul/sbr148 CrossRefGoogle Scholar
- Newcomer JW (2007) Metabolic syndrome and mental illness. Am J Manag Care 13:S170–S177Google Scholar
- Numakawa T, Adachi N, Richards M, Chiba S, Kunugi H (2013) Brain-derived neurotrophic factor and glucocorticoids: reciprocal influence on the central nervous system. Neuroscience 239:157–172. https://doi.org/10.1016/j.neuroscience.2012.09.073 CrossRefGoogle Scholar
- Ösby U, Correia N, Brandt L, et al (2000) Time trends in schizophrenia mortality in Stockholm County, Sweden: cohort study. Rapid diagnosis of falciparum malaria by using the Para Sight F test in travellers returning to the United Kingdom: prospective study 321:483–484Google Scholar
- Pandya CD, Hoda MN, Kutiyanawalla A, Buckley PF, Pillai A (2013) Differential effects upon brain and serum BDNF levels in rats as response to continuous and intermittent administration strategies of two second generation antipsychotics. Schizophr Res 151:287–288. https://doi.org/10.1016/j.schres.2013.09.027 CrossRefGoogle Scholar
- Rao JS, Kim HW, Harry GJ, Rapoport SI, Reese EA (2013) Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients. Schizophr Res 147:24–31. https://doi.org/10.1016/j.schres.2013.02.017 CrossRefGoogle Scholar
- Scharfman HE, MacLusky NJ (2008) Estrogen–growth factor interactions and their contributions to neurological disorders. Headache 48:S77–S89. https://doi.org/10.1111/j.1526-4610.2008.01200.x.Estrogen CrossRefGoogle Scholar
- Shugart YY, Chen L, Day INM, Lewis SJ, Timpson NJ, Yuan W, Abdollahi MR, Ring SM, Ebrahim S, Golding J, Lawlor DA, Davey-Smith G (2009) Two British women studies replicated the association between the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) and BMI. Eur J Hum Genet 17:1050–1055. https://doi.org/10.1038/ejhg.2008.272 CrossRefGoogle Scholar
- Spratt E, Granholm A-C, Carpenter LA, Boger H, Papa C, Logan S, Chaudhary H, Boatwright SW, Brady K (2015) Pilot study and review: physiological differences in BDNF, a potential biomarker in males and females with autistic disorder. Int Neuropsychiatr Dis J 3:19–26. https://doi.org/10.1016/B978-0-12-420118-7.00008-1.Dopamine CrossRefGoogle Scholar
- Tsai A, Liou YJ, Hong CJ, Wu CL, Tsai SJ, Bai YM (2011) Association study of brain-derived neurotrophic factor gene polymorphisms and body weight change in schizophrenic patients under long-term atypical antipsychotic treatment. NeuroMolecular Med 13:328–333. https://doi.org/10.1007/s12017-011-8159-5 CrossRefGoogle Scholar
- Xiu MH, Hui L, Dang YF, de Hou T, Zhang CX, Zheng YL, Chen DC, Kosten TR, Zhang XY (2009) Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Prog Neuro-Psychopharmacology Biol Psychiatry 33:1508–1512. https://doi.org/10.1016/j.pnpbp.2009.08.011 CrossRefGoogle Scholar
- Zai GCM, Zai CCH, Chowdhury NI, Tiwari AK, Souza RP, Lieberman JA, Meltzer HY, Potkin SG, Müller DJ, Kennedy JL (2012) The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain. Prog Neuro-Psychopharmacology Biol Psychiatry 39:96–101. https://doi.org/10.1016/j.pnpbp.2012.05.014 CrossRefGoogle Scholar
- Zhang X, Chen D, Xiu M, et al (2012b) Cognitive and serum BDNF correlates of BDNF Val66Met gene polymorphism in patients with schizophrenia and normal controls. Hum Genet 131:1187–1195. doi: https://doi.org/10.1007/s00439-012-1150-x.Cognitive
- Zhang XY, Zhou DF, Wu GY, Cao LY, Tan YL, Haile CN, Li J, Lu L, Kosten TA, Kosten TR (2008) BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia. Neuropsychopharmacology 33:2200–2205. https://doi.org/10.1038/sj.npp.1301619 CrossRefGoogle Scholar
- Zhou B, China CM-AG of the WG on O in (2002) Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults—study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Env Sci 15:83–96Google Scholar