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Understanding the Causal Relationships Between Opioid Dependence and Risk of Mental Disorders: A Comprehensive Two-Sample Mendelian Randomization Study

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Abstract

Observational studies have reported positive associations between opioid dependence and major mental disorders. However, the causal relationships and causal mechanisms between opioid dependence and mental disorders remain unknown due to potential confounding bias and reverse causality. In this study, we aim to investigate the causal associations and possible mediating mechanisms between opioid dependence and mental disorders via Mendelian randomization. Comprehensive bidirectional Mendelian randomization (MR) studies were conducted between opioid dependence and major mental disorders, including schizophrenia, bipolar disorder, major depressive disorder, panic disorder, anorexia, obsessive–compulsive disorder, post-traumatic stress disorder, and insomnia. Inverse variance weighted approach was adopted as the primary analytic method with series of sensitivity analyses. Mediation effects of chronic pain along the opioid dependence–mental disorders causal pathway were assessed by multivariate MR and two-step MR. Forward MR identified significant positive causal effects of opioid dependence on insomnia (OR = 1.03, 95% CI = (1.01, 1.05), p = 0.005), while reverse MR showed significant positive causal effects of schizophrenia on opioid dependence (OR = 1.20, 95% CI = (1.07, 1.34), p = 0.002). No significant causal associations were found between opioid dependence and other mental disorders. Neither opioid dependence on insomnia nor schizophrenia on opioid dependence causal pathway was significantly mediated by chronic pain. Higher risks of genetically predicted opioid dependence may lead to higher risks of insomnia, while higher risks of genetically predicted schizophrenia may lead to higher risks of developing opioid dependence. The majority of causal effects were acted directly rather than via chronic pain.

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Data Availability

The GWAS summary data of opioid dependence is available at https://www.ebi.ac.uk/gwas/studies/GCST90043725. The GWAS summary data of 8 mental disorders are available at https://figshare.com/articles/dataset/an2019/14671980; https://figshare.com/articles/dataset/bip2021_noUKBB/22564402; https://figshare.com/articles/dataset/MDD2_MDD2018_GWAS_sumstats_w_o_UKBB/21655784;  https://figshare.com/articles/dataset/ocd2018/14672103; https://figshare.com/articles/dataset/panic2019/16602218; https://figshare.com/articles/dataset/ptsd2019/14672133; https://figshare.com/articles/dataset/scz2022/19426775; https://research.23andme.com/collaborate/#publication. The GWAS summary data of chronic pain is available at https://www.ebi.ac.uk/gwas/studies/GCST90043740. Ethics statement All relevant GWAS had obtained ethical permissions from corresponding institutional review boards. Since our study involves only publicly available GWAS summary statistics, no ethical approval was required from the institutional review board.

References

  • Abdel-Baki, A., Ouellet-Plamondon, C., Salvat, É., Grar, K., & Potvin, S. (2017). Symptomatic and functional outcomes of substance use disorder persistence 2 years after admission to a first-episode psychosis program. Psychiatry Research, 247, 113–119.

    Article  PubMed  Google Scholar 

  • Amare, A. T., Vaez, A., Hsu, Y. H., Direk, N., Kamali, Z., Howard, D. M., ... & Hartman, C. A. (2020). Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression. Molecular psychiatry, 25(7), 1420–1429.

  • Arnold, P. D., Askland, K. D., Barlassina, C., Bellodi, L., Bienvenu, O. J., Black, D., ... & Zai, G. (2018). Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis. Molecular psychiatry, 23(5), 1181–1181.

  • Asaad, T. A., Ghanem, M. H., Samee, A. M. A., & El-Habiby, M. M. (2011). Sleep profile in patients with chronic opioid abuse: A polysomnographic evaluation in an Egyptian sample. Addictive Disorders & Their Treatment, 10(1), 21–28.

    Article  Google Scholar 

  • Barkus, E. (2016). High-potency cannabis increases the risk of psychosis. BMJ Ment Health, 19(2), 54–54.

    Google Scholar 

  • Battle, D. E. (2013). Diagnostic and statistical manual of mental disorders (DSM). In Codas, 25(2), 191–192.

    Google Scholar 

  • Burgess, S., & Thompson, S. G. (2017). Interpreting findings from Mendelian randomization using the MR-Egger method. European Journal of Epidemiology, 32, 377–389.

    Article  PubMed  PubMed Central  Google Scholar 

  • Burgess, S., Davies, N. M., & Thompson, S. G. (2016). Bias due to participant overlap in two-sample Mendelian randomization. Genetic Epidemiology, 40(7), 597–608.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cardno, A. G., & Owen, M. J. (2014). Genetic relationships between schizophrenia, bipolar disorder, and schizoaffective disorder. Schizophrenia Bulletin, 40(3), 504–515.

    Article  PubMed  PubMed Central  Google Scholar 

  • Carter, A. R., Sanderson, E., Hammerton, G., Richmond, R. C., Davey Smith, G., Heron, J., ... & Howe, L. D. (2021). Mendelian randomisation for mediation analysis: Current methods and challenges for implementation. European journal of epidemiology, 36(5), 465–478.

  • Chambers, R. A., Krystal, J. H., & Self, D. W. (2001). A neurobiological basis for substance abuse comorbidity in schizophrenia. Biological Psychiatry, 50(2), 71–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang, K. C., Lee, K. Y., Lu, T. H., Hwang, J. S., Lin, C. N., Ting, S. Y., ... & Wang, J. D. (2019). Opioid agonist treatment reduces losses in quality of life and quality-adjusted life expectancy in heroin users: Evidence from real world data. Drug and alcohol dependence, 201, 197–204.

  • Chiappelli, J., Chen, S., Hackman, A., & Hong, L. E. (2018). Evidence for differential opioid use disorder in schizophrenia in an addiction treatment population. Schizophrenia Research, 194, 26–31.

    Article  PubMed  Google Scholar 

  • Choi, K. W., Chen, C. Y., Stein, M. B., Klimentidis, Y. C., Wang, M. J., Koenen, K. C., & Smoller, J. W. (2019). Assessment of bidirectional relationships between physical activity and depression among adults: A 2-sample mendelian randomization study. JAMA Psychiatry, 76(4), 399–408.

    Article  PubMed  PubMed Central  Google Scholar 

  • Clark, S. D., & Abi-Dargham, A. (2019). The role of dynorphin and the kappa opioid receptor in the symptomatology of schizophrenia: A review of the evidence. Biological Psychiatry, 86(7), 502–511.

    Article  CAS  PubMed  Google Scholar 

  • Clark, S. D., Van Snellenberg, J. X., Lawson, J. M., & Abi-Dargham, A. (2020). Opioid antagonists are associated with a reduction in the symptoms of schizophrenia: A meta-analysis of controlled trials. Neuropsychopharmacology, 45(11), 1860–1869.

    Article  PubMed  PubMed Central  Google Scholar 

  • Davis, M. A., Lin, L. A., Liu, H., & Sites, B. D. (2017). Prescription opioid use among adults with mental health disorders in the United States. The Journal of the American Board of Family Medicine, 30(4), 407–417.

    Article  PubMed  Google Scholar 

  • Degenhardt, L., Grebely, J., Stone, J., Hickman, M., Vickerman, P., Marshall, B. D., ... & Larney, S. (2019). Global patterns of opioid use and dependence: Harms to populations, interventions, and future action. The Lancet, 394(10208), 1560–1579.

  • Dijkstra, B. A., De Jong, C. A., Krabbe, P. F., & van der Staak, C. P. (2008). Prediction of abstinence in opioid-dependent patients. Journal of Addiction Medicine, 2(4), 194–201.

    Article  PubMed  Google Scholar 

  • Dolsen, E. A., & Harvey, A. G. (2017). Life-time history of insomnia and hypersomnia symptoms as correlates of alcohol, cocaine and heroin use and relapse among adults seeking substance use treatment in the United States from 1991 to 1994. Addiction, 112(6), 1104–1111.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dowell, D., Arias, E., Kochanek, K., Anderson, R., Guy, G. P., Losby, J. L., & Baldwin, G. (2017). Contribution of opioid-involved poisoning to the change in life expectancy in the United States, 2000–2015. JAMA, 318(11), 1065–1067.

    Article  PubMed  PubMed Central  Google Scholar 

  • Dunn, K. E., Saulsgiver, K. A., Miller, M. E., Nuzzo, P. A., & Sigmon, S. C. (2015). Characterizing opioid withdrawal during double-blind buprenorphine detoxification. Drug and Alcohol Dependence, 151, 47–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farrell, M., Boys, A., Bebbington, P., Brugha, T., Coid, J., Jenkins, R., ... & Taylor, C. (2002). Psychosis and drug dependence: Results from a national survey of prisoners. The British Journal of Psychiatry, 181(5), 393–398.

  • Feingold, D., Brill, S., Goor-Aryeh, I., Delayahu, Y., & Lev-Ran, S. (2018). The association between severity of depression and prescription opioid misuse among chronic pain patients with and without anxiety: A cross-sectional study. Journal of Affective Disorders, 235, 293–302.

    Article  PubMed  Google Scholar 

  • Forstner, A. J., Awasthi, S., Wolf, C., Maron, E., Erhardt, A., Czamara, D., ... & Schumacher, J. (2021). Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression. Molecular psychiatry, 26(8), 4179–4190.

  • Gage, S. H., & Munafò, M. R. (2015). Rethinking the association between smoking and schizophrenia. The Lancet Psychiatry, 2(2), 118–119.

    Article  PubMed  Google Scholar 

  • Gage, S. H., Bowden, J., Davey Smith, G., & Munafò, M. R. (2018). Investigating causality in associations between education and smoking: A two-sample Mendelian randomization study. International Journal of Epidemiology, 47(4), 1131–1140.

    Article  PubMed  PubMed Central  Google Scholar 

  • Garland, E. L., Froeliger, B., Zeidan, F., Partin, K., & Howard, M. O. (2013). The downward spiral of chronic pain, prescription opioid misuse, and addiction: Cognitive, affective, and neuropsychopharmacologic pathways. Neuroscience & Biobehavioral Reviews, 37(10), 2597–2607.

    Article  Google Scholar 

  • Haack, M., Simpson, N., Sethna, N., Kaur, S., & Mullington, J. (2020). Sleep deficiency and chronic pain: Potential underlying mechanisms and clinical implications. Neuropsychopharmacology, 45(1), 205–216.

    Article  PubMed  Google Scholar 

  • Han, B., Compton, W. M., Jones, C. M., & Cai, R. (2015). Nonmedical prescription opioid use and use disorders among adults aged 18 through 64 years in the United States, 2003–2013. JAMA, 314(14), 1468–1478.

    Article  CAS  PubMed  Google Scholar 

  • Han, B., Jones, C. M., Blanco, C., & Compton, W. M. (2017). National trends in and correlates of nonmedical use of prescription stimulants, nonmedical use frequency, and use disorders. The Journal of Clinical Psychiatry, 78(9), 21718.

    Article  Google Scholar 

  • Hartwell, E. E., Pfeifer, J. G., McCauley, J. L., Moran-Santa Maria, M., & Back, S. E. (2014). Sleep disturbances and pain among individuals with prescription opioid dependence. Addictive Behaviors, 39(10), 1537–1542.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hjorthøj, C., Albert, N., & Nordentoft, M. (2018). Association of substance use disorders with conversion from schizotypal disorder to schizophrenia. JAMA Psychiatry, 75(7), 733–739.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huedo-Medina, T. B., Sánchez-Meca, J., Marín-Martínez, F., & Botella, J. (2006). Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychological Methods, 11(2), 193.

    Article  PubMed  Google Scholar 

  • Jiang, L., Zheng, Z., Fang, H., & Yang, J. (2021). A generalized linear mixed model association tool for biobank-scale data. Nature Genetics, 53(11), 1616–1621.

    Article  CAS  PubMed  Google Scholar 

  • Jones, C. M. (2018). Reprint of trends and key correlates of prescription opioid injection misuse in the United States. Addictive Behaviors, 86, 24–31.

    Article  PubMed  Google Scholar 

  • Jones, C. M., & McCance-Katz, E. F. (2019). Co-occurring substance use and mental disorders among adults with opioid use disorder. Drug and Alcohol Dependence, 197, 78–82.

    Article  PubMed  Google Scholar 

  • Kay, D. C., Pickworth, W. B., & Neider, G. L. (1981). Morphine-like insomnia from heroin in nondependent human addicts. British Journal of Clinical Pharmacology, 11(2), 159–169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kendler, K. S., Lönn, S. L., Sundquist, J., & Sundquist, K. (2015). Smoking and schizophrenia in population cohorts of Swedish women and men: A prospective co-relative control study. American Journal of Psychiatry, 172(11), 1092–1100.

    Article  PubMed  Google Scholar 

  • Khantzian, E. J. (1997). The self-medication hypothesis of substance use disorders: A reconsideration and recent applications. Harvard Review of Psychiatry, 4(5), 231–244.

    Article  CAS  PubMed  Google Scholar 

  • Ko, J. Y., Patrick, S. W., Tong, V. T., Patel, R., Lind, J. N., & Barfield, W. D. (2016). Incidence of neonatal abstinence syndrome—28 states, 1999–2013. Morbidity and Mortality Weekly Report, 65(31), 799–802.

    Article  PubMed  Google Scholar 

  • Koob, G. F. (2020). Neurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement. Biological Psychiatry, 87(1), 44–53.

    Article  CAS  PubMed  Google Scholar 

  • Li, K. J., Chen, A., & DeLisi, L. E. (2020). Opioid use and schizophrenia. Current Opinion in Psychiatry, 33(3), 219–224.

    Article  PubMed  Google Scholar 

  • Moore, J. T., & Kelz, M. B. (2009). Opiates, sleep, and pain: The adenosinergic link. The Journal of the American Society of Anesthesiologists, 111(6), 1175–1176.

    Google Scholar 

  • Morgan, P. T., Pace-Schott, E., Pittman, B., Stickgold, R., & Malison, R. T. (2010). Normalizing effects of modafinil on sleep in chronic cocaine users. American Journal of Psychiatry, 167(3), 331–340.

    Article  PubMed  Google Scholar 

  • Mueser, K. T., Yarnold, P. R., Levinson, D. F., Singh, H., Bellack, A. S., Kee, K., ... & Yadalam, K. G. (1990). Prevalence of substance abuse in schizophrenia: Demographic and clinical correlates. Schizophrenia bulletin, 16(1), 31–56.

  • Mullins, N., Forstner, A. J., O’Connell, K. S., Coombes, B., Coleman, J. R., Qiao, Z., ... & Potash, J. B. (2021). Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nature genetics, 53(6), 817–829.

  • Nievergelt, C. M., Maihofer, A. X., Klengel, T., Atkinson, E. G., Chen, C. Y., Choi, K. W., ... & Stevens, J. S. (2019). International meta-analysis of PTSD genome-wide association studies identifies sex-and ancestry-specific genetic risk loci. Nature communications, 10(1), 4558.

  • Nordmann, S., Lions, C., Vilotitch, A., Michel, L., Mora, M., Spire, B., ... & ANRS Methaville study group. (2016). A prospective, longitudinal study of sleep disturbance and comorbidity in opiate dependence (the ANRS Methaville study). Psychopharmacology, 233, 1203–1213.

  • Overdose, O. (2018). Understanding the epidemic. Centers for Disease Control and Prevention: Atlanta.

    Google Scholar 

  • Pasman, J. A., Verweij, K. J., Gerring, Z., Stringer, S., Sanchez-Roige, S., Treur, J. L., ... & Vink, J. M. (2018). GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability. Nature neuroscience, 21(9), 1161–1170.

  • Peters, P. J., Pontones, P., Hoover, K. W., Patel, M. R., Galang, R. R., Shields, J., ... & Duwve, J. M. (2016). HIV infection linked to injection use of oxymorphone in Indiana, 2014–2015. New England Journal of Medicine, 375(3), 229–239.

  • Pierce, B. L., & Burgess, S. (2013). Efficient design for Mendelian randomization studies: Subsample and 2-sample instrumental variable estimators. American Journal of Epidemiology, 178(7), 1177–1184.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pierce, B. L., Ahsan, H., & VanderWeele, T. J. (2011). Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. International Journal of Epidemiology, 40(3), 740–752.

    Article  PubMed  Google Scholar 

  • Regier, D. A., Farmer, M. E., Rae, D. S., Locke, B. Z., Keith, S. J., Judd, L. L., & Goodwin, F. K. (1990). Comorbidity of mental disorders with alcohol and other drug abuse: Results from the Epidemiologic Catchment Area (ECA) study. JAMA, 264(19), 2511–2518.

    Article  CAS  PubMed  Google Scholar 

  • Rosoff, D. B., Smith, G. D., & Lohoff, F. W. (2021). Prescription opioid use and risk for major depressive disorder and anxiety and stress-related disorders: A multivariable Mendelian randomization analysis. JAMA Psychiatry, 78(2), 151–160.

    Article  PubMed  Google Scholar 

  • Roth, T. (2009). Does effective management of sleep disorders reduce substance dependence? Drugs, 69, 65–75.

    Article  CAS  PubMed  Google Scholar 

  • Sayers, S. L., Campbell, E. C., Kondrich, J., Mann, S. C., Cornish, J., O’Brien, C., & Caroff, S. N. (2005). Cocaine abuse in schizophrenic patients treated with olanzapine versus haloperidol. The Journal of Nervous and Mental Disease, 193(6), 379–386.

    Article  PubMed  Google Scholar 

  • Schierenbeck, T., Riemann, D., Berger, M., & Hornyak, M. (2008). Effect of illicit recreational drugs upon sleep: Cocaine, ecstasy and marijuana. Sleep Medicine Reviews, 12(5), 381–389.

    Article  PubMed  Google Scholar 

  • Schulte, M. T., & Hser, Y. I. (2013). Substance use and associated health conditions throughout the lifespan. Public Health Reviews, 35(2), 1–27.

    Article  Google Scholar 

  • SCORE, U. R. A. P. (2018). Statistical inference in two-sample summary-data mendelian randomization using robust adjusted profile score. arXiv preprint arXiv:1801.09652.

  • Serdarevic, M., Osborne, V., Striley, C. W., & Cottler, L. B. (2017). The association between insomnia and prescription opioid use: Results from a community sample in Northeast Florida. Sleep Health, 3(5), 368–372.

    Article  PubMed  PubMed Central  Google Scholar 

  • Shaheed, C. A., McLachlan, A. J., & Maher, C. G. (2019). Rethinking “long term” opioid therapy. Bmj, 367.

  • Shaw, I. R., Lavigne, G., Mayer, P., & Choinière, M. (2005). Acute intravenous administration of morphine perturbs sleep architecture in healthy pain-free young adults: A preliminary study. Sleep, 28(6), 677–682.

    Article  PubMed  Google Scholar 

  • Shekhar, A. (2019). Role of kappa opioid receptors in symptoms of schizophrenia: What is the neurobiology? Biological Psychiatry, 86(7), 494–496.

    Article  PubMed  Google Scholar 

  • Skrivankova, V. W., Richmond, R. C., Woolf, B. A., Yarmolinsky, J., Davies, N. M., Swanson, S. A., ... & Richards, J. B. (2021). Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: The STROBE-MR statement. Jama, 326(16), 1614–1621.

  • Sullivan, M. D., Edlund, M. J., Zhang, L., Unützer, J., & Wells, K. B. (2006). Association between mental health disorders, problem drug use, and regular prescription opioid use. Archives of Internal Medicine, 166(19), 2087–2093.

    Article  PubMed  Google Scholar 

  • Tran, A., Fuller, J. M., Wong, K. K., Krass, I., Grunstein, R., & Saini, B. (2009). The development of a sleep disorder screening program in Australian community pharmacies. Pharmacy World & Science, 31, 473–480.

    Article  Google Scholar 

  • Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., ... & Lazzeroni, L. C. (2022). Map** genomic loci implicates genes and synaptic biology in schizophrenia. Nature, 604(7906), 502–508.

  • Vekaria, V., Bose, B., Murphy, S. M., Avery, J., Alexopoulos, G., & Pathak, J. (2021). Association of co-occurring opioid or other substance use disorders with increased healthcare utilization in patients with depression. Translational Psychiatry, 11(1), 265.

    Article  PubMed  PubMed Central  Google Scholar 

  • Verbanck, M., Chen, C. Y., Neale, B., & Do, R. (2018). Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nature Genetics, 50(5), 693–698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, D., & Teichtahl, H. (2007). Opioids, sleep architecture and sleep-disordered breathing. Sleep Medicine Reviews, 11(1), 35–46.

    Article  PubMed  Google Scholar 

  • Watanabe, K., Jansen, P. R., Savage, J. E., Nandakumar, P., Wang, X., Hinds, D. A., ... & Posthuma, D. (2022). Genome-wide meta-analysis of insomnia prioritizes genes associated with metabolic and psychiatric pathways. Nature genetics, 54(8), 1125–1132.

  • Watkins, A., John, A., Bradshaw, C., Jones, J., & Jones, M. (2019). Schizophrenia in high risk opioid users: A short communication on an autopsy study. Psychiatry Research, 276, 112–114.

    Article  PubMed  Google Scholar 

  • Watson, H. J., Yilmaz, Z., Thornton, L. M., Hübel, C., Coleman, J. R., Gaspar, H. A., ... & Seitz, J. (2019). Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature genetics, 51(8), 1207–1214.

  • Wray, N. R., Ripke, S., Mattheisen, M., Trzaskowski, M., Byrne, E. M., Abdellaoui, A., ... & Viktorin, A. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature genetics, 50(5), 668–681.

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Acknowledgements

The authors thank the National Natural Science Foundation of China and Shanghai Science and Technology Commission for supporting this study.

Funding

This work is supported by the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 82304241) and the General Projects of Shanghai Science and Technology Commission (Grant No. 21ZR1405000).

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  1. School of Data Science, Fudan University, Shanghai, China

    Yundi Hu, Luheng Qian, Runye Shi & Xiaolei Lin

  2. Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China

    Haojing Duan

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XL contributed to the conception and design of the study. YH and LQ participated in the assessments and data extraction processes. YH, RS, and HD performed the statistical analyses. XL and YH discussed the results and wrote the original draft of the manuscript. XL performed the review and editing. XL supervised the project and contributed to the funding acquisition. All authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the finalized manuscript.

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Hu, Y., Qian, L., Shi, R. et al. Understanding the Causal Relationships Between Opioid Dependence and Risk of Mental Disorders: A Comprehensive Two-Sample Mendelian Randomization Study. Int J Ment Health Addiction (2024). https://doi.org/10.1007/s11469-024-01315-y

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