The BDNF Val66Met polymorphism serves as a potential marker of body weight in patients with psychiatric disorders

Yinghua Zhang; Xinyue Wei; Wenhao Zhang; Feng Jin; Wenbo Cao; Mingjin Yue; Saijun Mo; Yinghua Zhang; Xinyue Wei; Wenhao Zhang; Feng Jin; Wenbo Cao; Mingjin Yue; Saijun Mo

doi:10.3934/Neuroscience.2024012

AIMS Neuroscience

2024, Volume 11, Issue 2: 188-202. doi: 10.3934/Neuroscience.2024012

Previous Article Next Article

Review Topical Sections

The BDNF Val66Met polymorphism serves as a potential marker of body weight in patients with psychiatric disorders

1.
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
2.
Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China
3.
State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou, China
4.
Henan Tianxing Education and Media Company, Limited, Zhengzhou, China
Yinghua Zhang, Xinyue Wei, and Wenhao Zhang contributed equally to this work.

Received: 19 December 2023 Revised: 13 June 2024 Accepted: 17 June 2024 Published: 24 June 2024

Brain-derived neurotrophic factor (BDNF) is a predominant neurotrophic factor in the brain, indispensable for neuronal growth, synaptic development, neuronal repair, and hippocampal neuroplasticity. Among its genetic variants, the BDNF Val66Met polymorphism is widespread in the population and has been associated with the onset and aggravation of diverse pathologies, including metabolic conditions like obesity and diabetes, cardiovascular ailments, cancer, and an array of psychiatric disorders. Psychiatric disorders constitute a broad category of mental health issues that influence mood, cognition, and behavior. Despite advances in research and treatment, challenges persist that hinder our understanding and effective intervention of these multifaceted conditions. Achieving and maintaining stable body weight is pivotal for overall health and well-being, and the relationship between psychiatric conditions and body weight is notably intricate and reciprocal. Both weight gain and loss have been linked to varying mental health challenges, making the disentanglement of this relationship critical for crafting holistic treatment strategies. The BDNF Val66Met polymorphism's connection to weight fluctuation in psychiatric patients has garnered attention. This review investigated the effects and underlying mechanisms by which the BDNF Val66Met polymorphism moderates body weight among individuals with psychiatric disorders. It posits the polymorphism as a potential biomarker, offering prospects for improved monitoring and therapeutic approaches for mental illnesses.
- BDNF,
- Val66Met polymorphism,
- body weight,
- psychiatric disorders,
- marker
Citation: Yinghua Zhang, Xinyue Wei, Wenhao Zhang, Feng Jin, Wenbo Cao, Mingjin Yue, Saijun Mo. The BDNF Val66Met polymorphism serves as a potential marker of body weight in patients with psychiatric disorders[J]. AIMS Neuroscience, 2024, 11(2): 188-202. doi: 10.3934/Neuroscience.2024012

Related Papers:

Abstract

Brain-derived neurotrophic factor (BDNF) is a predominant neurotrophic factor in the brain, indispensable for neuronal growth, synaptic development, neuronal repair, and hippocampal neuroplasticity. Among its genetic variants, the BDNF Val66Met polymorphism is widespread in the population and has been associated with the onset and aggravation of diverse pathologies, including metabolic conditions like obesity and diabetes, cardiovascular ailments, cancer, and an array of psychiatric disorders. Psychiatric disorders constitute a broad category of mental health issues that influence mood, cognition, and behavior. Despite advances in research and treatment, challenges persist that hinder our understanding and effective intervention of these multifaceted conditions. Achieving and maintaining stable body weight is pivotal for overall health and well-being, and the relationship between psychiatric conditions and body weight is notably intricate and reciprocal. Both weight gain and loss have been linked to varying mental health challenges, making the disentanglement of this relationship critical for crafting holistic treatment strategies. The BDNF Val66Met polymorphism's connection to weight fluctuation in psychiatric patients has garnered attention. This review investigated the effects and underlying mechanisms by which the BDNF Val66Met polymorphism moderates body weight among individuals with psychiatric disorders. It posits the polymorphism as a potential biomarker, offering prospects for improved monitoring and therapeutic approaches for mental illnesses.

Acknowledgments

This study was supported by Foundation of Henan Educational Committee, grant number 22A310024, Natural Science Foundation for Young Teachers' Basic Research of Zhengzhou University, grant number JC202035025, and College Student Innovation and Entrepreneurship Competitions, grant number 2023CXCY401, 2024CXCY504 and 202410459164.

Conflict of interest

The authors declare no conflicts of interest.

Author contributions

Study conception and design: Saijun Mo, Wenbo Cao; Draft manuscript preparation: Yinghua Zhang, Xinyue Wei, Wenhao Zhang; Data collection: Feng Jin, Mingjin Yue; Review and editing: Saijun Mo. All authors reviewed and approved the final version of the manuscript.

References

[1]	Kowiański P, Lietzau G, Czuba E, et al. (2018) BDNF: A Key Factor with Multipotent Impact on Brain Signaling and Synaptic Plasticity. Cell Mol Neurobiol 38: 579-593. http://doi.org/10.1007/s10571-017-0510-4
[2]	Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64: 238-258. http://doi.org/10.1124/pr.111.005108
[3]	Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14: 7-23. http://doi.org/10.1038/nrn3379
[4]	Greenberg ME, Xu B, Lu B, et al. (2009) New insights in the biology of BDNF synthesis and release: implications in CNS function. J Neurosci 29: 12764-12767. http://doi.org/10.1523/jneurosci.3566-09.2009
[5]	Tsai A, Liou YJ, Hong CJ, et al. (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. http://doi.org/10.1007/s12017-011-8159-5
[6]	Zai GC, Zai CC, Chowdhury NI, et al. (2012) The role of brain-derived neurotrophic factor (BDNF) gene variants in antipsychotic response and antipsychotic-induced weight gain. Prog Neuropsychopharmacol Biol Psychiatry 39: 96-101. http://doi.org/10.1016/j.pnpbp.2012.05.014
[7]	Herrfurth N, Volckmar AL, Peters T, et al. (2018) Relevance of polymorphisms in MC4R and BDNF in short normal stature. BMC Pediatr 18: 278. http://doi.org/10.1186/s12887-018-1245-1
[8]	Clarke J, Ramoz N, Fladung AK, et al. (2016) Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism. Transl Psychiatry 6: e829. http://doi.org/10.1038/tp.2016.98
[9]	Morales-Marín ME, Genis-Mendoza AD, Tovilla-Zarate CA, et al. (2016) Association between obesity and the brain-derived neurotrophic factor gene polymorphism Val66Met in individuals with bipolar disorder in Mexican population. Neuropsychiatr Dis Treat 12: 1843-1848. http://doi.org/10.2147/ndt.S104654
[10]	Monteleone P, Maj M (2008) Genetic susceptibility to eating disorders: associated polymorphisms and pharmacogenetic suggestions. Pharmacogenomics 9: 1487-1520. http://doi.org/10.2217/14622416.9.10.1487
[11]	Raspopow K, Abizaid A, Matheson K, et al. (2010) Psychosocial stressor effects on cortisol and ghrelin in emotional and non-emotional eaters: influence of anger and shame. Horm Behav 58: 677-684. http://doi.org/10.1016/j.yhbeh.2010.06.003
[12]	Kokkinos A, le Roux CW, Alexiadou K, et al. (2010) Eating slowly increases the postprandial response of the anorexigenic gut hormones, peptide YY and glucagon-like peptide-1. J Clin Endocrinol Metab 95: 333-337. http://doi.org/10.1210/jc.2009-1018
[13]	Karl JP, Young AJ, Rood JC, et al. (2013) Independent and combined effects of eating rate and energy density on energy intake, appetite, and gut hormones. Obesity (Silver Spring) 21: E244-252. http://doi.org/10.1002/oby.20075
[14]	Schlienz NJ, Huhn AS, Speed TJ, et al. (2018) Double jeopardy: a review of weight gain and weight management strategies for psychotropic medication prescribing during methadone maintenance treatment. Int Rev Psychiatry 30: 147-154. http://doi.org/10.1080/09540261.2018.1509843
[15]	Suriyaprom K, Tungtrongchitr R, Thawnashom K, et al. (2013) BDNF Val66Met polymorphism and serum concentrations of BDNF with smoking in Thai males. Genet Mol Res 12: 4925-4933. http://doi.org/10.4238/2013.October.24.3
[16]	Kang JI, Kim SJ, Song YY, et al. (2013) Genetic influence of COMT and BDNF gene polymorphisms on resilience in healthy college students. Neuropsychobiology 68: 174-180. http://doi.org/10.1159/000353257
[17]	Egan MF, Kojima M, Callicott JH, et al. (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112: 257-269. http://doi.org/10.1016/s0092-8674(03)00035-7
[18]	Björkholm C, Monteggia LM (2016) BDNF - a key transducer of antidepressant effects. Neuropharmacology 102: 72-79. http://doi.org/10.1016/j.neuropharm.2015.10.034
[19]	Wheeler AL, Felsky D, Viviano JD, et al. (2018) BDNF-Dependent Effects on Amygdala-Cortical Circuitry and Depression Risk in Children and Youth. Cereb Cortex 28: 1760-1770. http://doi.org/10.1093/cercor/bhx086
[20]	Shen T, You Y, Joseph C, et al. (2018) BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders. Aging Dis 9: 523-536. http://doi.org/10.14336/ad.2017.0717
[21]	De Meo E, Portaccio E, Prestipino E, et al. (2022) Effect of BDNF Val66Met polymorphism on hippocampal subfields in multiple sclerosis patients. Mol Psychiatry 27: 1010-1019. http://doi.org/10.1038/s41380-021-01345-1
[22]	Lim YY, Villemagne VL, Laws SM, et al. (2014) Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study. PLoS One 9: e86498. http://doi.org/10.1371/journal.pone.0086498
[23]	Lim YY, Maruff P, Barthélemy NR, et al. (2022) Association of BDNF Val66Met With Tau Hyperphosphorylation and Cognition in Dominantly Inherited Alzheimer Disease. JAMA Neurol 79: 261-270. http://doi.org/10.1001/jamaneurol.2021.5181
[24]	Ramezani M, Ruskey JA, Martens K, et al. (2020) Association Between BDNF Val66Met Polymorphism and Mild Behavioral Impairment in Patients With Parkinson's Disease. Front Neurol 11: 587992. http://doi.org/10.3389/fneur.2020.587992
[25]	Farcas A, Hindmarch C, Iftene F (2023) BDNF gene Val66Met polymorphisms as a predictor for clinical presentation in schizophrenia - recent findings. Front Psychiatry 14: 1234220. http://doi.org/10.3389/fpsyt.2023.1234220
[26]	Pathak P, Mehra A, Ram S, et al. (2022) Association of serum BDNF level and Val66Met polymorphism with response to treatment in patients of major depressive disease: A step towards personalized therapy. Behav Brain Res 430: 113931. http://doi.org/10.1016/j.bbr.2022.113931
[27]	González-Castro TB, Pool-García S, Tovilla-Zárate CA, et al. (2019) Association between BDNF Val66Met polymorphism and generalized anxiety disorder and clinical characteristics in a Mexican population: A case-control study. Medicine (Baltimore) 98: e14838. http://doi.org/10.1097/md.0000000000014838
[28]	Taj MJR, Ganesh S, Shukla T, et al. (2018) BDNF gene and obsessive compulsive disorder risk, symptom dimensions and treatment response. Asian J Psychiatr 38: 65-69. http://doi.org/10.1016/j.ajp.2017.10.014
[29]	Li C, Zeng X, Liu Z, et al. (2018) BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles. Cell Physiol Biochem 45: 366-377. http://doi.org/10.1159/000486908
[30]	Lan B, Lv D, Sun X, et al. (2022) Genetic Variations in IFNGR1, BDNF and IL-10 May Predict the Susceptibility to Depression and Anxiety in Chinese Women With Breast Cancer. Clin Breast Cancer 22: 674-680. http://doi.org/10.1016/j.clbc.2022.07.002
[31]	Yap NY, Tan NYT, Tan CJ, et al. (2020) Associations of plasma brain-derived neurotrophic factor (BDNF) and Val66Met polymorphism (rs6265) with long-term cancer-related cognitive impairment in survivors of breast cancer. Breast Cancer Res Treat 183: 683-696. http://doi.org/10.1007/s10549-020-05807-y
[32]	Jiang H, Wang R, Liu Y, et al. (2009) BDNF Val66Met polymorphism is associated with unstable angina. Clin Chim Acta 400: 3-7. http://doi.org/10.1016/j.cca.2008.10.017
[33]	Raucci FJ, Singh AP, Soslow J, et al. (2020) The BDNF rs6265 Polymorphism is a Modifier of Cardiomyocyte Contractility and Dilated Cardiomyopathy. Int J Mol Sci 21. http://doi.org/10.3390/ijms21207466
[34]	Abaj F, Rafiee M, Koohdani F (2022) Interactions of dietary insulin index and dietary insulin load with brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in relation to cardiometabolic markers in Iranian diabetic patients: a cross-sectional study. Br J Nutr 128: 785-792. http://doi.org/10.1017/s0007114521003974
[35]	Naeini Z, Abaj F, Rafiee M, et al. (2023) Interactions of BDNF Val66met and dietary indices in relation to metabolic markers among patient with type 2 diabetes mellitus: a cross-sectional study. J Health Popul Nutr 42: 34. http://doi.org/10.1186/s41043-023-00375-5
[36]	Chaldakov GN, Tonchev AB, Aloe L (2009) NGF and BDNF: from nerves to adipose tissue, from neurokines to metabokines. Riv Psichiatr 44: 79-87.
[37]	Nicholson JR, Peter JC, Lecourt AC, et al. (2007) Melanocortin-4 receptor activation stimulates hypothalamic brain-derived neurotrophic factor release to regulate food intake, body temperature and cardiovascular function. J Neuroendocrinol 19: 974-982. http://doi.org/10.1111/j.1365-2826.2007.01610.x
[38]	Pivac N, Nikolac M, Nedic G, et al. (2011) Brain derived neurotrophic factor Val66Met polymorphism and psychotic symptoms in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 35: 356-362. http://doi.org/10.1016/j.pnpbp.2010.10.020
[39]	Huang E, Hettige NC, Zai G, et al. (2019) BDNF Val66Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizoaffective disorder patients: a meta-analysis. Pharmacogenomics J 19: 269-276. http://doi.org/10.1038/s41397-018-0041-5
[40]	McIntyre RS, Danilewitz M, Liauw SS, et al. (2010) Bipolar disorder and metabolic syndrome: an international perspective. J Affect Disord 126: 366-387. http://doi.org/10.1016/j.jad.2010.04.012
[41]	Jauhar S, Johnstone M, McKenna PJ (2022) Schizophrenia. Lancet 399: 473-486. http://doi.org/10.1016/s0140-6736(21)01730-x
[42]	Bonaccorso S, Sodhi M, Li J, et al. (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. http://doi.org/10.1111/bdi.12294
[43]	Zhang XY, Zhou DF, Wu GY, et al. (2008) BDNF levels and genotype are associated with antipsychotic-induced weight gain in patients with chronic schizophrenia. Neuropsychopharmacology 33: 2200-2205. http://doi.org/10.1038/sj.npp.1301619
[44]	Treasure J, Duarte TA, Schmidt U (2020) Eating disorders. Lancet 395: 899-911. http://doi.org/10.1016/s0140-6736(20)30059-3
[45]	Day J, Ternouth A, Collier DA (2009) Eating disorders and obesity: two sides of the same coin?. Epidemiol Psichiatr Soc 18: 96-100. https://doi.org/10.1017/S1121189X00000956
[46]	Kaplan AS, Levitan RD, Yilmaz Z, et al. (2008) A DRD4/BDNF gene-gene interaction associated with maximum BMI in women with bulimia nervosa. Int J Eat Disord 41: 22-28. http://doi.org/10.1002/eat.20474
[47]	Smith DJ, Whitham EA, Ghaemi SN (2012) Bipolar disorder. Handb Clin Neurol 106: 251-263. http://doi.org/10.1016/b978-0-444-52002-9.00015-2
[48]	Unger TJ, Calderon GA, Bradley LC, et al. (2007) Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. J Neurosci 27: 14265-14274. http://doi.org/10.1523/jneurosci.3308-07.2007
[49]	Schramm E, Klein DN, Elsaesser M, et al. (2020) Review of dysthymia and persistent depressive disorder: history, correlates, and clinical implications. Lancet Psychiatry 7: 801-812. http://doi.org/10.1016/s2215-0366(20)30099-7
[50]	Pérez-Gutiérrez AM, Rovira P, Gutiérrez B, et al. (2024) Influence of BDNF Val66Met genetic polymorphism in Major Depressive Disorder and Body Mass Index: Evidence from a meta-analysis of 6481 individuals. J Affect Disord 344: 458-465. http://doi.org/10.1016/j.jad.2023.10.024
[51]	Zhou JX, Li HC, Bai XJ, et al. (2013) Functional Val66Met polymorphism of Brain-derived neurotrophic factor in type 2 diabetes with depression in Han Chinese subjects. Behav Brain Funct 9: 34. http://doi.org/10.1186/1744-9081-9-34
[52]	Cervin M (2023) Obsessive-Compulsive Disorder: Diagnosis, Clinical Features, Nosology, and Epidemiology. Psychiatr Clin North Am 46: 1-16. http://doi.org/10.1016/j.psc.2022.10.006
[53]	Timpano KR, Schmidt NB, Wheaton MG, et al. (2011) Consideration of the BDNF gene in relation to two phenotypes: hoarding and obesity. J Abnorm Psychol 120: 700-707. http://doi.org/10.1037/a0024159
[54]	Mestre-Bach G, Potenza MN (2023) Neural mechanisms linked to treatment outcomes and recovery in substance-related and addictive disorders. Dialogues Clin Neurosci 25: 75-91. http://doi.org/10.1080/19585969.2023.2242359
[55]	Lecerf JM (2014) Smoking cessation and weight gain. From one addiction to another?. Soins : 2s11-14.
[56]	Rasmussen M, Hovhannisyan K, Adami J, et al. (2021) Characteristics of Patients in Treatment for Alcohol and Drug Addiction Who Succeed in Changing Smoking, Weight, and Physical Activity: A Secondary Analysis of an RCT on Combined Lifestyle Interventions. Eur Addict Res 27: 123-130. http://doi.org/10.1159/000510608
[57]	Gülü M, Yagin FH, Gocer I, et al. (2023) Exploring obesity, physical activity, and digital game addiction levels among adolescents: A study on machine learning-based prediction of digital game addiction. Front Psychol 14: 1097145. http://doi.org/10.3389/fpsyg.2023.1097145
[58]	Tayhan Kartal F, Yabancı Ayhan N (2021) Relationship between eating disorders and internet and smartphone addiction in college students. Eat Weight Disord 26: 1853-1862. http://doi.org/10.1007/s40519-020-01027-x
[59]	Ali AM, Hori H, Kim Y, et al. (2021) Predictors of Nutritional Status, Depression, Internet Addiction, Facebook Addiction, and Tobacco Smoking Among Women With Eating Disorders in Spain. Front Psychiatry 12: 735109. http://doi.org/10.3389/fpsyt.2021.735109
[60]	Lang UE, Sander T, Lohoff FW, et al. (2007) Association of the met66 allele of brain-derived neurotrophic factor (BDNF) with smoking. Psychopharmacology (Berl) 190: 433-439. http://doi.org/10.1007/s00213-006-0647-1
[61]	He L, Liao Y, Wu Q, et al. (2020) Association Between Brain-Derived Neurotrophic Factor Val66Met Polymorphism and Methamphetamine Use Disorder: A Meta-Analysis. Front Psychiatry 11: 585852. http://doi.org/10.3389/fpsyt.2020.585852
[62]	Hori H, Kim Y (2019) Inflammation and post-traumatic stress disorder. Psychiatry Clin Neurosci 73: 143-153. http://doi.org/10.1111/pcn.12820
[63]	Hoerster KD, Tanksley L, Sulayman N, et al. (2021) Testing a tailored weight management program for veterans with PTSD: The MOVE! + UP randomized controlled trial. Contemp Clin Trials 107: 106487. http://doi.org/10.1016/j.cct.2021.106487
[64]	Nagai M, Ohira T, Maeda M, et al. (2021) The association between body mass index and recovery from post-traumatic stress disorder after the nuclear accident in Fukushima. Sci Rep 11: 5330. http://doi.org/10.1038/s41598-021-84644-5
[65]	Takemoto E, Van Oss KR, Chamany S, et al. (2021) Post-traumatic stress disorder and the association with overweight, obesity, and weight change among individuals exposed to the World Trade Center disaster, 2003-2016. Psychol Med 51: 2647-2656. http://doi.org/10.1017/s0033291720001208
[66]	Rippey CS, Pietrzak RH, Maruff P, et al. (2022) Interactive effects of the BDNF Val66Met polymorphism and posttraumatic stress disorder on cognition in U.S. military veterans. Psychoneuroendocrinology 142: 105820. http://doi.org/10.1016/j.psyneuen.2022.105820
[67]	Castillo-Navarrete JL, Vicente B, Schmidt K, et al. (2023) Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population. PeerJ 11: e15870. http://doi.org/10.7717/peerj.15870
[68]	Tudor L, Konjevod M, Nikolac Perkovic M, et al. (2018) Genetic Variants of the Brain-Derived Neurotrophic Factor and Metabolic Indices in Veterans With Posttraumatic Stress Disorder. Front Psychiatry 9: 637. http://doi.org/10.3389/fpsyt.2018.00637
[69]	Ando T, Ishikawa T, Hotta M, et al. (2012) No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese. Am J Med Genet B Neuropsychiatr Genet 159b: 48-52. http://doi.org/10.1002/ajmg.b.32000
[70]	Liu J, Wang P, Sun L, et al. (2021) The association between BDNF levels and risperidone-induced weight gain is dependent on the BDNF Val66Met polymorphism in antipsychotic-naive first episode schizophrenia patients: a 12-week prospective study. Transl Psychiatry 11: 458. http://doi.org/10.1038/s41398-021-01585-3
[71]	Monteleone P, Zanardini R, Tortorella A, et al. (2006) The 196G/A (val66met) polymorphism of the BDNF gene is significantly associated with binge eating behavior in women with bulimia nervosa or binge eating disorder. Neurosci Lett 406: 133-137. http://doi.org/10.1016/j.neulet.2006.07.040
[72]	Ribasés M, Gratacòs M, Fernández-Aranda F, et al. (2004) Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations. Hum Mol Genet 13: 1205-1212. http://doi.org/10.1093/hmg/ddh137

Reader Comments

Your name:*

Email:*
© 2024 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)