1
Department of Psychiatry, All India Institute of Medical Sciences, Delhi, India
2
National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, Delhi, India
10.34172/ahj.1593
Abstract
Background: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity and survival. The BDNF gene Val66Met polymorphism is hypothesized to be linked with alcohol dependence syndrome (ADS). We studied the relationship between the BDNF Val66Met polymorphism and the clinical features of ADS, including severity, craving, and perceived stress among alcohol-dependent patients. Methods: In this cross-sectional study on treatment-seeking north Indian male ADS patients aged 18 to 60 years, alcohol dependence severity (Severity of Alcohol Dependence Questionnaire, SADQ), craving (obsessive compulsive drinking scale), and perceived stress (perceived stress scale-4) were measured. The genetic analysis for calculating the BDNF Val66Met allele frequency was carried out using TaqMan assays. Statistical analysis was done using SPSS Version 26. Findings: The participants’ mean age (SD) (n = 80) was 37 ± 8.52 years. Half of the participants had tobacco dependence, too. Almost half of the participants showed alcohol dependence with mild severity. The mean OCDS and PSS-4 scores were 26.08 ± 9.34 and 9.08 ± 2.4, respectively. The allelic frequency of the Val and Met alleles were 73.1% and 26.9%, respectively. Among the Met allele carriers, the OCDS (P = 0.02) and PSS-4 scores (P = 0.03) were significantly higher than observed in the Val group patients. Conclusion: The study concludes that BDNF gene Val66Met polymorphism could impact clinical variables such as craving and perceived stress in alcohol-dependent subjects. It merits the use of genetic analysis in determining the course of clinical maintenance of alcohol-dependent patients.
Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015;11(6):1164-78. doi: 10.5114/aoms.2015.56342.
Lipsky RH, Marini AM. Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Ann N Y Acad Sci. 2007;1122:130-43. doi: 10.1196/annals.1403.009.
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.
Guillin O, Diaz J, Carroll P, Griffon N, Schwartz JC, Sokoloff P. BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature. 2001;411(6833):86-9. doi: 10.1038/35075076.
Pandey SC. A Critical role of brain-derived neurotrophic factor in alcohol consumption. Biol Psychiatry. 2016;79(6):427-9. doi: 10.1016/j.biopsych.2015.12.020.
Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, et al. The BDNF Val66Met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003;112(2):257-69. doi: 10.1016/s0092-8674(03)00035-7.
Pattwell SS, Bath KG, Perez-Castro R, Lee FS, Chao MV, Ninan I. The BDNF Val66Met polymorphism impairs synaptic transmission and plasticity in the infralimbic medial prefrontal cortex. J Neurosci. 2012;32(7):2410-21. doi: 10.1523/ jneurosci.5205-11.2012.
Warnault V, Darcq E, Morisot N, Phamluong K, Wilbrecht L, Massa SM, et al. The BDNF valine 68 to methionine polymorphism increases compulsive alcohol drinking in mice that is reversed by tropomyosin receptor kinase B activation. Biol Psychiatry. 2016;79(6):463-73. doi: 10.1016/j. biopsych.2015.06.007 .
Ambekar A, Agrawal A, Rao R, Mishra AK, Khandelwal SK, Chadda RK. Magnitude of Substance Use in India. New Delhi: Ministry of Social Justice and Empowerment, Government of India; 2019.
Pivac N, Kim B, Nedić G, Joo YH, Kozarić-Kovacić D, Hong JP, et al. Ethnic differences in brain-derived neurotrophic factor Val66Met polymorphism in Croatian and Korean healthy participants. Croat Med J. 2009;50(1):43-8. doi: 10.3325/ cmj.2009.50.43.
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989;84(11):1353-7. doi: 10.1111/j.1360- 0443.1989.tb00737.x.
Stockwell T, Murphy D, Hodgson R. The severity of alcohol dependence questionnaire: its use, reliability and validity. Br J Addict. 1983;78(2):145-55. doi: 10.1111/j.1360-0443.1983. tb05502.x.
Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995;19(1):92-9. doi: 10.1111/j.1530-0277.1995. tb01475.x.
Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385-96.
Pangtey R, Basu S, Meena GS, Banerjee B. Perceived stress and its epidemiological and behavioral correlates in an urban area of Delhi, India: a community-based cross-sectional study. Indian J Psychol Med. 2020;42(1):80-6. doi: 10.4103/ijpsym. Ijpsym_528_18.
Ramawat RB, Quraishi R, Deep R, Kumar R, Mishra AK, Jain R. An observational case-control study for BDNF Val66Met polymorphism and serum BDNF in patients with major depressive disorder (MDD). Indian J Psychol Med. 2024:02537176241280050. doi: 10.1177/02537176241280050.
Verhulst B, Neale MC, Kendler KS. The heritability of alcohol use disorders: a meta-analysis of twin and adoption studies. Psychol Med. 2015;45(5):1061-72. doi: 10.1017/ s0033291714002165.
Ahmadiantehrani S, Warnault V, Legastelois R, Ron D. From signaling pathways to behavior: the light and dark sides of alcohol. In: Nohrona AB, Cui C, Harris RA, Crabbe JC, eds. Neurobiology of Alcohol Dependence. Elsevier; 2014. p. 155- 71.
Altar CA, Fritsche M, Lindsay RM. Cell body infusions of brain-derived neurotrophic factor increase forebrain dopamine release and serotonin metabolism determined with in vivo microdialysis. Adv Pharmacol. 1998;42:915-21. doi: 10.1016/s1054-3589(08)60896-0.
Ebadi M, Ramana Kumari MV, Hiramatsu M, Hao R, Pfeiffer RF, Rojas P. Metallothionein, neurotrophins and selegiline in providing neuroprotection in Parkinson’s disease. Restor Neurol Neurosci. 1998;12(2-3):103-11.
Mizui T, Tanima Y, Komatsu H, Kumanogoh H, Kojima M. The biological actions and mechanisms of brain-derived neurotrophic factor in healthy and disordered brains. Neurosci Med. 2014;5(4):183-95. doi: 10.4236/nm.2014.54021.
Alonso M, Vianna MR, Depino AM, Mello e Souza T, Pereira P, Szapiro G, et al. BDNF-triggered events in the rat hippocampus are required for both short- and long-term memory formation. Hippocampus. 2002;12(4):551-60. doi: 10.1002/hipo.10035.
Colzato LS, Van der Does AJ, Kouwenhoven C, Elzinga BM, Hommel B. BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults. Psychoneuroendocrinology. 2011;36(10):1562-9. doi: 10.1016/j.psyneuen.2011.04.010.
Matsushita S, Kimura M, Miyakawa T, Yoshino A, Murayama M, Masaki T, et al. Association study of brain-derived neurotrophic factor gene polymorphism and alcoholism. Alcohol Clin Exp Res. 2004;28(11):1609-12. doi: 10.1097/01. alc.0000145697.81741.d2.
Grzywacz A, Samochowiec A, Ciechanowicz A, Samochowiec J. Family-based study of brain-derived neurotrophic factor (BDNF) gene polymorphism in alcohol dependence. Pharmacol Rep. 2010;62(5):938-41. doi: 10.1016/s1734- 1140(10)70354-6.
Mo M, Fu XY, Zhang XL, Zhang SC, Zhang HQ, Wu L, et al. Association of plasma pro-brain-derived neurotrophic factor (proBDNF)/mature brain-derived neurotrophic factor (mBDNF) levels with BDNF gene Val66Met polymorphism in alcohol dependence. Med Sci Monit. 2021;27:e930421. doi: 10.12659/msm.930421.
Tsai SJ. Critical issues in BDNF Val66Met genetic studies of neuropsychiatric disorders. Front Mol Neurosci. 2018;11:156. doi: 10.3389/fnmol.2018.00156.
Klimkiewicz A, Mach A, Jakubczyk A, Klimkiewicz J, Wnorowska A, Kopera M, et al. COMT and BDNF gene variants help to predict alcohol consumption in alcohol-dependent patients. J Addict Med. 2017;11(2):114-8. doi: 10.1097/adm.0000000000000277.
Quraishi R, Sharma J, Jain R, Ambekar A. Influence of catechol-O-methyltransferase enzyme gene polymorphism on alcohol and tobacco consumption in North Indian treatment seeking population. Indian J Psychiatry. 2021;63(3):240-4. doi: 10.4103/psychiatry.IndianJPsychiatry_465_20.
Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, et al. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004;24(18):4401-11. doi: 10.1523/jneurosci.0348-04.2004.
Lyons WE, Mamounas LA, Ricaurte GA, Coppola V, Reid SW, Bora SH, et al. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities. Proc Natl Acad Sci U S A. 1999;96(26):15239-44. doi: 10.1073/pnas.96.26.15239.
Lu L, Dempsey J, Liu SY, Bossert JM, Shaham Y. A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal. J Neurosci. 2004;24(7):1604-11. doi: 10.1523/jneurosci.5124-03.2004.
Moffat JJ, Sakhai SA, Hoisington ZW, Ehinger Y, Ron D. The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice. Psychopharmacology (Berl). 2023;240(2):303-17. doi: 10.1007/s00213-022-06305-3.
Wojnar M, Brower KJ, Strobbe S, Ilgen M, Matsumoto H, Nowosad I, et al. Association between Val66Met brain-derived neurotrophic factor (BDNF) gene polymorphism and post-treatment relapse in alcohol dependence. Alcohol Clin Exp Res. 2009;33(4):693-702. doi: 10.1111/j.1530- 0277.2008.00886.x.
Costa MA, Girard M, Dalmay F, Malauzat D. Brain-derived neurotrophic factor serum levels in alcohol-dependent subjects 6 months after alcohol withdrawal. Alcohol Clin Exp Res. 2011;35(11):1966-73. doi: 10.1111/j.1530- 0277.2011.01548.x.
Heberlein A, Muschler M, Wilhelm J, Frieling H, Lenz B, Gröschl M, et al. BDNF and GDNF serum levels in alcohol-dependent patients during withdrawal. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(6):1060-4. doi: 10.1016/j.pnpbp.2010.05.025.
Huang MC, Chen CH, Chen CH, Liu SC, Ho CJ, Shen WW, et al. Alterations of serum brain-derived neurotrophic factor levels in early alcohol withdrawal. Alcohol Alcohol. 2008;43(3):241-5. doi: 10.1093/alcalc/agm172.
Zanardini R, Fontana A, Pagano R, Mazzaro E, Bergamasco F, Romagnosi G, et al. Alterations of brain-derived neurotrophic factor serum levels in patients with alcohol dependence. Alcohol Clin Exp Res. 2011;35(8):1529-33. doi: 10.1111/j.1530-0277.2011.01489.x.
Elzinga BM, Molendijk ML, Oude Voshaar RC, Bus BA, Prickaerts J, Spinhoven P, et al. The impact of childhood abuse and recent stress on serum brain-derived neurotrophic factor and the moderating role of BDNF Val66Met. Psychopharmacology (Berl). 2011;214(1):319-28. doi: 10.1007/s00213-010-1961-1.
Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E. Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res. 2005;53(2):129-39. doi: 10.1016/j.neures.2005.06.008.
Forero DA, López-León S, Shin HD, Park BL, Kim DJ. Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence. Drug Alcohol Depend. 2015;149:259- 63. doi: 10.1016/j.drugalcdep.2015.01.017.
Su N, Zhang L, Fei F, Hu H, Wang K, Hui H, et al. The brain-derived neurotrophic factor is associated with alcohol dependence-related depression and antidepressant response. Brain Res. 2011;1415:119-26. doi: 10.1016/j. brainres.2011.08.005.
Bagri, S., QURAISHI, R., Kumar, R., Singh, S., & Ambekar, A. (2025). Brain-Derived Neurotrophic Factor Gene Polymorphism, Craving, and Stress Among Alcohol-Dependent Patients: A Preliminary Cross-sectional Study from India. Addiction & Health, 17(1), 1-7. doi: 10.34172/ahj.1593
MLA
Shubha Bagri; RIZWANA QURAISHI; Ram Kumar; Shalini Singh; Atul Ambekar. "Brain-Derived Neurotrophic Factor Gene Polymorphism, Craving, and Stress Among Alcohol-Dependent Patients: A Preliminary Cross-sectional Study from India", Addiction & Health, 17, 1, 2025, 1-7. doi: 10.34172/ahj.1593
HARVARD
Bagri, S., QURAISHI, R., Kumar, R., Singh, S., Ambekar, A. (2025). 'Brain-Derived Neurotrophic Factor Gene Polymorphism, Craving, and Stress Among Alcohol-Dependent Patients: A Preliminary Cross-sectional Study from India', Addiction & Health, 17(1), pp. 1-7. doi: 10.34172/ahj.1593
VANCOUVER
Bagri, S., QURAISHI, R., Kumar, R., Singh, S., Ambekar, A. Brain-Derived Neurotrophic Factor Gene Polymorphism, Craving, and Stress Among Alcohol-Dependent Patients: A Preliminary Cross-sectional Study from India. Addiction & Health, 2025; 17(1): 1-7. doi: 10.34172/ahj.1593