Interactive effects of ARRB2 and CHRNA5 genetic polymorphisms on cognitive function in Chinese male methamphetamine use disorder patients
Linjun Jiang MS
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorCorresponding Author
Dongmei Wang PhD
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Correspondence Dongmei Wang, PhD, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Xiang-Yang Zhang, MD, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Search for more papers by this authorYang Tian PhD
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorJiajing Chen MS
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorMengqian Qu MS
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorLianglun Jia BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorFabing Fu BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorShanshan Tang BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorXiaotao Wang BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorCorresponding Author
Xiang-Yang Zhang MD
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Correspondence Dongmei Wang, PhD, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Xiang-Yang Zhang, MD, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Search for more papers by this authorLinjun Jiang MS
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorCorresponding Author
Dongmei Wang PhD
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Correspondence Dongmei Wang, PhD, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Xiang-Yang Zhang, MD, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Search for more papers by this authorYang Tian PhD
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorJiajing Chen MS
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorMengqian Qu MS
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorLianglun Jia BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorFabing Fu BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorShanshan Tang BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorXiaotao Wang BS
Xin Hua Drug Rehabilitation Center, Sichuan, China
Search for more papers by this authorCorresponding Author
Xiang-Yang Zhang MD
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
Correspondence Dongmei Wang, PhD, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Xiang-Yang Zhang, MD, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd, Chaoyang District, Beijing 100101, China.
Email: [email protected]
Search for more papers by this authorAbstract
Background and Objectives
Both β-arrestin2 and nicotinic acetylcholine receptor (nAChR) have been implicated in cognitive processes, particularly in relation to psychiatric disorders, including addiction. Previous studies have suggested that nAChR may be regulated by β-arrestin2. However, no study has investigated the interaction of β-arrestin2 and nAChR on cognition. We aimed to examine the main and interactive effects of their respective encoding genes, ARRB2 and CHRNA5, on cognitive function in MUD patients.
Methods
We recruited 559 patients with methamphetamine use disorder (MUD) and 459 healthy controls, assessed their cognitive functioning using the Chinese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and genotyped ARRB2 rs1045280 and CHRNA5 rs3829787 polymorphisms in MUD patients.
Results
Compared to healthy controls, MUD patients scored significantly lower on all RBANS indexes. Neither ARRB2 rs1045280 nor CHRNA5 rs3829787 had main effects on cognitive function in MUD patients, but there were significant interactive effects between the two single nucleotide polymorphisms (SNPs) on multiple RBANS indexes, including immediate memory, visuospatial/constructional, delayed memory, and total score. In detail, among carriers of CHRNA5 rs3829787 T allele, ARRB2 rs1045280 TT carriers had higher RBANS scores than the C allele carriers, whereas among carriers of CHRNA5 rs3829787 CC genotype, ARRB2 rs1045280 TT carriers performed worse in RBANS.
Conclusions and Scientific Significance
Our study identified for the first time an interactive effect between ARRB2 and CHRNA5 on cognitive function in MUD patients, which would enlarge our knowledge of genetic interaction on cognitive function.
DECLARATION OF INTEREST
The authors declare no conflicts of interest. The authors are resonsible for the content and writing of this paper, and the content and the results have not been submitted or published elsewhere.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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REFERENCES
- 1 United Nations Office on Drugs and Crime, 2023. World Drug Report 2023.
- 2 China National Narcotics Control Committee, 2023. The 2022 Report of Drug Situation in China.
- 3Mizoguchi H, Yamada K. Methamphetamine use causes cognitive impairment and altered decision-making. Neurochem Int. 2019; 124: 106-113. doi:10.1016/j.neuint.2018.12.019
- 4Potvin S, Pelletier J, Grot S, Hébert C, Barr AM, Lecomte T. Cognitive deficits in individuals with methamphetamine use disorder: a meta-analysis. Addict Behav. 2018; 80: 154-160. doi:10.1016/j.addbeh.2018.01.021
- 5Sabrini S, Wang GY, Lin JC, Ian JK, Curley LE. Methamphetamine use and cognitive function: a systematic review of neuroimaging research. Drug Alcohol Depend. 2019; 194: 75-87. doi:10.1016/j.drugalcdep.2018.08.041
- 6Sofuoglu M, DeVito EE, Waters AJ, Carroll KM. Cognitive enhancement as a treatment for drug addictions. Neuropharmacology. 2013; 64(1): 452-463. doi:10.1016/j.neuropharm.2012.06.021
- 7Natarajan R, Yamamoto BK. The basal ganglia as a substrate for the multiple actions of amphetamines. Basal ganglia. 2011; 1(2): 49-57. doi:10.1016/j.baga.2011.05.003
- 8Shukla M, Vincent B. Methamphetamine abuse disturbs the dopaminergic system to impair hippocampal-based learning and memory: an overview of animal and human investigations. Neurosci Biobehav Rev. 2021; 131: 541-559. doi:10.1016/j.neubiorev.2021.09.016.35
- 9Leung C, Wong Y. Role of G protein-coupled receptors in the regulation of structural plasticity and cognitive function. Molecules. 2017; 22(7):1239. doi:10.3390/molecules22071239
- 10Ma L, Pei G. β-arrestin signaling and regulation of transcription. J Cell Sci. 2007; 120(pt 2): 213-218. doi:10.1242/jcs.03338
- 11Hatzipantelis CJ, Lu Y, Spark DL, Langmead CJ, Stewart GD. β-Arrestin-2-dependent mechanism of GPR52 signaling in frontal cortical neurons. ACS Chem Neurosci. 2020; 11(14): 2077-2084. doi:10.1021/acschemneuro.0c00199
- 12Stoppel LJ, Auerbach BD, Senter RK, Preza AR, Lefkowitz RJ, Bear MF. β-Arrestin2 couples metabotropic glutamate receptor 5 to neuronal protein synthesis and is a potential target to treat fragile X. Cell Rep. 2017; 18(12): 2807-2814. doi:10.1016/j.celrep.2017.02.075
- 13Urs NM, Peterson SM, Caron MG. New concepts in dopamine D2 receptor biased signaling and implications for schizophrenia therapy. Biol Psychiatry. 2017; 81(1): 78-85. doi:10.1016/j.biopsych.2016.10.011
- 14Chen X, Gao R, Song Y, et al. Astrocytic AT1R deficiency ameliorates Aβ-induced cognitive deficits and synaptotoxicity through β-arrestin2 signaling. Prog Neurobiol. 2023; 228:102489. doi:10.1016/j.pneurobio.2023.102489
- 15Smucny J, Maddock RJ. Spectroscopic meta-analyses reveal novel metabolite profiles across methamphetamine and cocaine substance use disorder. Drug Alcohol Depend. 2023; 248:109900. doi:10.1016/j.drugalcdep.2023.109900
- 16Panmak P, Nopparat C, Permpoonpattana K, Namyen J, Govitrapong P. Melatonin protects against methamphetamine-induced Alzheimer's disease-like pathological changes in rat hippocampus. Neurochem Int. 2021; 148:105121. doi:10.1016/j.neuint.2021.105121
- 17Mihailescu S, Drucker-Colı́n R. Nicotine, brain nicotinic receptors, and neuropsychiatric disorders. Arch Med Res. 2000; 31(2): 131-144. doi:10.1016/s0188-4409(99)00087-9
- 18Jones S, Sudweeks S, Yakel JL. Nicotinic receptors in the brain: correlating physiology with function. Trends Neurosci. 1999; 22(12): 555-561. doi:10.1016/s0166-2236(99)01471-x
- 19Mansvelder HD, van Aerde KI, Couey JJ, Brussaard AB. Nicotinic modulation of neuronal networks: from receptors to cognition. Psychopharmacology. 2006; 184(3-4): 292-305. doi:10.1007/s00213-005-0070-z
- 20dos Santos Coura R, Granon S. Prefrontal neuromodulation by nicotinic receptors for cognitive processes. Psychopharmacology. 2012; 221(1): 1-18. doi:10.1007/s00213-011-2596-6
- 21Bloem B, Poorthuis RB, Mansvelder HD. Cholinergic modulation of the medial prefrontal cortex: the role of nicotinic receptors in attention and regulation of neuronal activity. Front Neural Circuits. 2014; 8:17. doi:10.3389/fncir.2014.00017
- 22Bye LJ, Finol-Urdaneta RK, Tae HS, Adams DJ. Nicotinic acetylcholine receptors: key targets for attenuating neurodegenerative diseases. Int J Biochem Cell Biol. 2023; 157:106387. doi:10.1016/j.biocel.2023.106387
- 23Howe WM, Brooks JL, Tierney PL, et al. α5 nAChR modulation of the prefrontal cortex makes attention resilient. Brain Struct Funct. 2018; 223(2): 1035-1047. doi:10.1007/s00429-017-1601-1
- 24Terry AV, Callahan PM. Nicotinic acetylcholine receptor ligands, cognitive function, and preclinical approaches to drug discovery. Nicotine & Tobacco Res. 2019; 21(3): 383-394. doi:10.1093/ntr/nty166
- 25Koukouli F, Rooy M, Tziotis D, et al. Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nature Med. 2017; 23(3): 347-354. doi:10.1038/nm.4274
- 26Lefkowitz RJ, Rajagopal K, Whalen EJ. New roles for β-Arrestins in cell signaling: not just for seven-transmembrane receptors. Mol Cell. 2006; 24(5): 643-652. doi:10.1016/j.molcel.2006.11.007
- 27Scholze P, Huck S. The α5 nicotinic acetylcholine receptor subunit differentially modulates α4β2* and α3β4* receptors. Front Synaptic Neurosci. 2020; 12:607959. doi:10.3389/fnsyn.2020.607959
- 28Zheng X, Duan W, Xu J, et al. Functionally significant nicotine acetylcholine receptor subunit α5 promoter haplotypes are associated with susceptibility to lung cancer in Chinese. Cancer. 2011; 117(20): 4714-4723. doi:10.1002/cncr.26017
- 29Hjorthøj CR, Hjorthøj AR, Nordentoft M. Validity of timeline follow-back for self-reported use of cannabis and other illicit substances—systematic review and meta-analysis. Addict Behav. 2012; 37(3): 225-233. doi:10.1016/j.addbeh.2011.11.025
- 30Shabani A, Masoumian S, Zamirinejad S, Hejri M, Pirmorad T, Yaghmaeezadeh H. Psychometric properties of structured clinical interview for DSM-5 disorders-clinician version (SCID-5-CV). Brain Behav. 2021; 11(5):e01894. doi:10.1002/brb3.1894
- 31Randolph C, Tierney MC, Mohr E, Chase TN. The repeatable battery for the assessment of neuropsychological status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998; 20(3): 310-319. doi:10.1076/jcen.20.3.310.823
- 32Cheng Y, Wu W, Wang J, Feng W, Wu X, Li C. Reliability and validity of the repeatable battery for the assessment of neuropsychological status in community-dwelling elderly. Arch Med Sci. 2011; 7(5): 850-857. doi:10.5114/aoms.2011.25561
- 33Zhang BH, Tan YL, Zhang WF, et al. Repeatable battery for the assessment of neuropsychological status as a screening test in Chinese: reliability and validity. Chinese Mental Health J. 2008; 22(12): 865-869.
- 34Ikeda M, Ozaki N, Suzuki T, et al. Possible association of β-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia. Genes Brain Behav. 2007; 6(1): 107-112. doi:10.1111/j.1601-183X.2006.00237.x
- 35Di Giorgio A, Smith RM, Fazio L, et al. DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory. PLoS One. 2014; 9(5):e95997. doi:10.1371/journal.pone.0095997
- 36Inden M, Takata K, Yanagisawa D, et al. α4 Nicotinic acetylcholine receptor modulated by galantamine on nigrostriatal terminals regulates dopamine receptor-mediated rotational behavior. Neurochem Int. 2016; 94: 74-81. doi:10.1016/j.neuint.2016.02.008
- 37Mamaligas AA, Cai Y, Ford CP. Nicotinic and opioid receptor regulation of striatal dopamine D2-receptor mediated transmission. Sci Rep. 2016; 6:37834. doi:10.1038/srep37834
- 38Bono F, Mutti V, Fiorentini C, Missale C. Dopamine D3 receptor heteromerization: implications for neuroplasticity and neuroprotection. Biomolecules. 2020; 10(7):1016. doi:10.3390/biom10071016
- 39Grieder TE, George O, Yee M, et al. Deletion of α5 nicotine receptor subunits abolishes nicotinic aversive motivational effects in a manner that phenocopies dopamine receptor antagonism. Eur J Neurosci. 2017; 46(1): 1673-1681. doi:10.1111/ejn.13605
- 40Cools R, Robbins TW. Chemistry of the adaptive mind. Philos Trans Royal Soc London Ser A: Math, Phys Engineer Sci. 2004; 362(1825): 2871-2888. doi:10.1098/rsta.2004.1468
- 41Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F. Addiction: beyond dopamine reward circuitry. Proc Natl Acad Sci. 2011; 108(37): 15037-15042. doi:10.1073/pnas.1010654108
- 42Oneda B, Crettol S, Bochud M, et al. β-Arrestin2 influences the response to methadone in opioid-dependent patients. Pharmacogenomics J. 2011; 11(4): 258-266. doi:10.1038/tpj.2010.37
- 43Ozberk D, Haywood A, Sutherland HG, et al. Association of polymorphisms in ARRB2 and clinical response to methadone for pain in advanced cancer. Pharmacogenomics. 2022; 23(5): 281-289. doi:10.2217/pgs-2021-0139
- 44Jiang T, Yu JT, Wang YL, et al. The genetic variation of ARRB2 is associated with late-onset Alzheimer's disease in Han Chinese. Curr Alzheimer Res. 2014; 11(4): 408-412. doi:10.2174/1567205011666140317095014
- 45Karavidha KK, Burmeister M, Greenwald MK. β-Arrestin 2 (ARRB2) polymorphism is associated with adverse consequences of chronic heroin use. Am J Addict. 2021; 30(4): 351-357. doi:10.1111/ajad.13150
- 46Liou YJ, Wang YC, Chen JY, et al. The coding-synonymous polymorphism rs1045280 (Ser280Ser) inβ-arrestin 2(ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia. Eur J Neurol. 2008; 15(12): 1406-1408. doi:10.1111/j.1468-1331.2008.02316.x
- 47Jean-Charles PY, Kaur S, Shenoy SK. G Protein-Coupled receptor signaling through β-arrestin-dependent mechanisms. J Cardiovasc Pharmacol. 2017; 70(3): 142-158. doi:10.1097/FJC.0000000000000482
- 48Ramos-Loyo J, González-Garrido AA, Llamas-Alonso LA, Sequeira H. Sex differences in cognitive processing: an integrative review of electrophysiological findings. Biol Psychol. 2022; 172:108370. doi:10.1016/j.biopsycho.2022.108370
- 49Weiss E, Deisenhammer E, Hinterhuber H, Marksteiner J. Geschlechtsunterschiede kognitiver leistungen -- populärwissenschaftliche stereotypien oder evidenzbasierte studienergebnisse? [Gender differences in cognitive functions] Fortschritte der Neurologie · Psychiatrie. 2005; 73(10): 587-595. doi:10.1055/s-2004-830296
