The Effects of BDNF Rs6265 and FGF21 Rs11665896 Polymorphisms on Alcohol Use Disorder-related Impulsivity in Han Chinese Adults

Overview

Journal Front Psychiatry

Specialty Psychiatry

Date 2024 May 9

PMID 38721616

Authors

Shizhuo Yang

Fan Wang

Lanrong Sun

Xinqian Liu

Siyuan Li

Yingjie Chen

Lingling Chen

Zeheng Pan

Yimin Kang

Yu-Hsin Chen

Wei Wang

Li Chen

Xiaokun Li

Chonghui Tang

Yanlong Liu

Affiliations

Soon will be listed here.

Abstract

Introduction: Patients with alcohol use disorder (AUD) often experience repeated withdrawal. Impulsivity is the most relevant factor influencing successful withdrawal. Brain-derived neurotrophic factor (BNDF) and fibroblast growth factor 21 (FGF21) are associated with impulsivity. Previous studies on the differential effects of BDNF or FGF21 on impulsivity have focused on single-gene effects and have inconsistent results. We aim to investigate the effects of BDNF rs6265 and FGF21 rs11665896, individually and together, on impulsivity during alcohol withdrawal in patients with AUD.

Methods: We recruited 482 adult Han Chinese males with AUD and assessed their impulsivity using the Barratt Impulsivity Scale. Genomic DNA was extracted and genotyped from peripheral blood samples. Statistical analysis was conducted on the data.

Results: The T-test and 2 × 2 analysis of variance were used to investigate the effects of the genes on impulsivity. There was a significant BDNF × FGF21 interaction on no-planning impulsiveness ( = 9.15, = 0.003, = 0.03). Simple main effects analyses and planned comparisons showed that BDNF rs6265 A allele × FGF21 rs11665896 T allele was associated with higher no-planning impulsiveness. Finally, hierarchical regression analyses revealed that only the interaction of BDNF and FGF21 accounted for a significant portion of the variance in no-planning impulsiveness.

Conclusion And Significance: The combination of BDNF rs6265 A allele and FGF21 rs11665896 T allele may increase impulsivity and discourage alcohol withdrawal. Our study provides a possible genetic explanation for the effects of associated impulsivity in patients with AUD from the perspective of gene-gene interactions.

References

Li S, Lu C, Kang L, Li Q, Chen H, Zhang H . Study on correlations of BDNF, PI3K, AKT and CREB levels with depressive emotion and impulsive behaviors in drug-naïve patients with first-episode schizophrenia. BMC Psychiatry. 2023; 23(1):225. PMC: 10071748. DOI: 10.1186/s12888-023-04718-8. View

Logrip M, Barak S, Warnault V, Ron D . Corticostriatal BDNF and alcohol addiction. Brain Res. 2015; 1628(Pt A):60-7. PMC: 4577309. DOI: 10.1016/j.brainres.2015.03.025. View

Warnault V, Darcq E, Morisot N, Phamluong K, Wilbrecht L, Massa S . The BDNF Valine 68 to Methionine Polymorphism Increases Compulsive Alcohol Drinking in Mice That Is Reversed by Tropomyosin Receptor Kinase B Activation. Biol Psychiatry. 2015; 79(6):463-73. PMC: 4676961. DOI: 10.1016/j.biopsych.2015.06.007. View

Kang K, Xu P, Wang M, Chunyu J, Sun X, Ren G . FGF21 attenuates neurodegeneration through modulating neuroinflammation and oxidant-stress. Biomed Pharmacother. 2020; 129:110439. DOI: 10.1016/j.biopha.2020.110439. View

Papachristou H, Nederkoorn C, Havermans R, van der Horst M, Jansen A . Can't stop the craving: the effect of impulsivity on cue-elicited craving for alcohol in heavy and light social drinkers. Psychopharmacology (Berl). 2011; 219(2):511-8. PMC: 3249167. DOI: 10.1007/s00213-011-2240-5. View

Ruiz-Padilla A, Morales-Hernandez G, Ruiz-Noa Y, Alonso-Castro A, Lazo-de-la-Vega-Monroy M, Preciado-Puga M . Association of the 3'UTR polymorphism (rs11665896) in the FGF21 gene with metabolic status and nutrient intake in children with obesity. J Pediatr Endocrinol Metab. 2019; 32(9):921-928. DOI: 10.1515/jpem-2018-0546. View

Russo-Neustadt A . Brain-derived neurotrophic factor, behavior, and new directions for the treatment of mental disorders. Semin Clin Neuropsychiatry. 2003; 8(2):109-18. DOI: 10.1053/scnp.2003.50014. View

Lu H, Jia C, Wu D, Jin H, Lin Z, Pan J . Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway. Cell Death Dis. 2021; 12(10):865. PMC: 8460788. DOI: 10.1038/s41419-021-04157-x. View

Sliedrecht W, Roozen H, Witkiewitz K, de Waart R, Dom G . The Association Between Impulsivity and Relapse in Patients With Alcohol Use Disorder: A Literature Review. Alcohol Alcohol. 2020; 56(6):637-650. DOI: 10.1093/alcalc/agaa132. View

10.

Lemonde S, Turecki G, Bakish D, Du L, Hrdina P, Bown C . Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci. 2003; 23(25):8788-99. PMC: 6740417. View

11.

Peregud D, Korolkov A, Baronets V, Lobacheva A, Arkus M, Igumnov S . [Contents of BDNF, miR-30a-5p and miR-122 during alcohol withdrawal syndrome]. Biomed Khim. 2022; 68(3):218-227. DOI: 10.18097/PBMC20226803218. View

12.

Kia-Keating B, Glatt S, Tsuang M . Meta-analyses suggest association between COMT, but not HTR1B, alleles, and suicidal behavior. Am J Med Genet B Neuropsychiatr Genet. 2007; 144B(8):1048-53. DOI: 10.1002/ajmg.b.30551. View

13.

Ambrus L, Sunnqvist C, Ekman R, Traskman-Bendz L, Westrin A . Plasma Brain-Derived Neurotrophic Factor and Psychopathology in Attempted Suicide. Neuropsychobiology. 2016; 73(4):241-8. DOI: 10.1159/000446286. View

14.

Yie J, Wang W, Deng L, Tam L, Stevens J, Chen M . Understanding the physical interactions in the FGF21/FGFR/β-Klotho complex: structural requirements and implications in FGF21 signaling. Chem Biol Drug Des. 2012; 79(4):398-410. DOI: 10.1111/j.1747-0285.2012.01325.x. View

15.

Zhou Z, Roy A, Lipsky R, Kuchipudi K, Zhu G, Taubman J . Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations. Arch Gen Psychiatry. 2005; 62(10):1109-18. DOI: 10.1001/archpsyc.62.10.1109. View

16.

Stanley B, Michel C, Galfalvy H, Keilp J, Rizk M, Richardson-Vejlgaard R . Suicidal subtypes, stress responsivity and impulsive aggression. Psychiatry Res. 2019; 280:112486. PMC: 7027392. DOI: 10.1016/j.psychres.2019.112486. View

17.

Hu A, Jiang H, Dowling R, Guo L, Zhao X, Hao W . The transition of alcohol control in China 1990-2019: Impacts and recommendations. Int J Drug Policy. 2022; 105:103698. PMC: 9247746. DOI: 10.1016/j.drugpo.2022.103698. View

18.

Su H, Tao J, Zhang J, Xie Y, Sun Y, Li L . An association between BDNF Val66Met polymorphism and impulsivity in methamphetamine abusers. Neurosci Lett. 2014; 582:16-20. DOI: 10.1016/j.neulet.2014.08.030. View

19.

Gao X, Dong W, Xia C, Ma Z, Wang Y, Sarra S . Centranthera grandiflore alleviates alcohol-induced oxidative stress and cell apoptosis. Chin J Nat Med. 2022; 20(8):572-579. DOI: 10.1016/S1875-5364(22)60181-X. View

20.

Dukic M, Radonjic T, Jovanovic I, Zdravkovic M, Todorovic Z, Kraisnik N . Alcohol, Inflammation, and Microbiota in Alcoholic Liver Disease. Int J Mol Sci. 2023; 24(4). PMC: 9966185. DOI: 10.3390/ijms24043735. View