Hostname: page-component-848d4c4894-x5gtn Total loading time: 0 Render date: 2024-05-14T04:33:25.665Z Has data issue: false hasContentIssue false
  • English
  • Français

Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence

Published online by Cambridge University Press:  09 June 2020

Hannah J. Jones Open the ORCID record for Hannah J. Jones [Opens in a new window] ,
Gemma Hammerton ,
Tayla McCloud ,
Lindsey A. Hines ,
Caroline Wright ,
Suzanne H. Gage ,
Peter Holmans ,
Peter B Jones ,
George Davey Smith  and
David E. J. Linden
...Show all authors
Hannah J. Jones*
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, University of Bristol, Bristol, UK
Gemma Hammerton
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK
Tayla McCloud
Affiliation:
Division of Psychiatry, University College London, London, UK
Lindsey A. Hines
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK
Caroline Wright
Affiliation:
Population Health Sciences, Bristol Medical School, University of Bristol, UK
Suzanne H. Gage
Affiliation:
Department of Psychological Sciences, University of Liverpool, Liverpool, UK
Peter Holmans
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Peter B Jones
Affiliation:
Department of Psychiatry, University of Cambridge, Cambridge, UK
George Davey Smith
Affiliation:
Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK
David E. J. Linden
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Michael C. O'Donovan
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Michael J. Owen
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
James T. Walters
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
Marcus R. Munafò
Affiliation:
Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK UK Centre for Tobacco and Alcohol Studies, School of Psychological Science, University of Bristol, UK
Jon Heron
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol, UK
Stanley Zammit
Affiliation:
Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, UK Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK
*
Author for correspondence: Hannah J. Jones, E-mail: hannah.jones@bristol.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.

Methods

Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.

Results

The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.

Conclusions

Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

Keywords

ALSPACcannabis-usecigarette-usemediationpolygenic scoreschizophrenia
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 1 , January 2022 , pp. 132 - 139
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Amos, A., Wiltshire, S., Bostock, Y., Haw, S., & McNeill, A. (2004). 'You can't go without a fag … you need it for your hash' - a qualitative exploration of smoking, cannabis and young people. Addiction, 99(1), 77–81. doi:10.1111/j.1360-0443.2004.00531.x.CrossRefGoogle Scholar
Baron-Cohen, S., & Wheelwright, S. (2003). The friendship questionnaire: An investigation of adults with Asperger syndrome or high-functioning autism, and normal sex differences. Journal of Autism and Developmental Disorders, 33(5), 509–517. doi:10.1023/a:1025879411971.CrossRefGoogle ScholarPubMed
Boyd, A., Golding, J., Macleod, J., Lawlor, D. A., Fraser, A., Henderson, J., … Davey Smith, G. (2013). Cohort profile: The ‘children of the 90s’ - the index offspring of the Avon Longitudinal Study of Parents and Children. International Journal of Epidemiology, 42, 111–127. doi:10.1093/ije/dys064.CrossRefGoogle ScholarPubMed
Cannon, M., Walsh, E., Hollis, C., Kargin, M., Taylor, E., Murray, R. M., & Jones, P. B. (2001). Predictors of later schizophrenia and affective psychosis among attendees at a child psychiatry department. British Journal of Psychiatry, 178, 420–426. doi:10.1192/bjp.178.5.420.CrossRefGoogle Scholar
Carey, C. E., Agrawal, A., Bucholz, K. K., Hartz, S. M., Lynskey, M. T., Nelson, E. C., … Bogdan, R. (2016). Associations between polygenic risk for psychiatric disorders and substance involvement. Frontiers in Genetics, 7, 149. doi:10.3389/fgene.2016.00149.CrossRefGoogle ScholarPubMed
Chang, C. C., Chow, C. C., Tellier, L. C. A. M., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015). Second-generation PLINK: Rising to the challenge of larger and richer datasets. Gigascience, 4, 7. doi:10.1186/s13742-015-0047-8.CrossRefGoogle ScholarPubMed
Courtney, K. E., Mejia, M. H., & Jacobus, J. (2017). Longitudinal studies on the etiology of cannabis use disorder: A review. Current addiction reports, 4(2), 43–52. doi:10.1007/s40429-017-0133-3.CrossRefGoogle ScholarPubMed
Davey Smith, G., & Hemani, G. (2014). Mendelian randomization: Genetic anchors for causal inference in epidemiological studies. Human Molecular Genetics, 23(R1), R89–R98. doi:10.1093/hmg/ddu328.CrossRefGoogle ScholarPubMed
de Leon, J., & Diaz, F. J. (2005). A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophrenia Research, 76(2–3), 135–157. doi:10.1016/j.schres.2005.02.010.CrossRefGoogle ScholarPubMed
Dickerson, F., Stallings, C. R., Origoni, A. E., Vaughan, C., Khushalani, S., Schroeder, J., & Yolken, R. H. (2013). Cigarette smoking among persons with schizophrenia or bipolar disorder in routine clinical settings, 1999–2011. Psychiatric Services, 64(1), 44–50. doi:10.1176/appi.ps.001432012.CrossRefGoogle ScholarPubMed
D'Souza, D. C., Perry, E., MacDougall, L., Ammerman, Y., Cooper, T., Wu, Y. T., … Krystal, J. H. (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacology, 29(8), 1558–1572. doi:10.1038/sj.npp.1300496.CrossRefGoogle Scholar
Fraser, A., Macdonald-Wallis, C., Tilling, K., Boyd, A., Golding, J., Davey Smith, G., … Lawlor, D. A. (2013). Cohort profile: The avon longitudinal study of parents and children: ALSPAC mothers cohort. International Journal of Epidemiology, 42, 97–110. doi:10.1093/ije/dys066.CrossRefGoogle ScholarPubMed
Gage, S. H., Davey Smith, G., Ware, J. J., Flint, J., & Munafò, M. R. (2016). G = E: What GWAS can tell us about the environment. Plos Genetics, 12, 2. doi:10.1371/journal.pgen.1005765.Google Scholar
Gage, S. H., Hickman, M., Heron, J., Munafo, M. R., Lewis, G., Macleod, J., & Zammit, S. (2014). Associations of cannabis and cigarette use with psychotic experiences at age 18: Findings from the Avon Longitudinal Study of Parents and Children. Psychological Medicine, 44(16), 3435–3444. doi:10.1017/S0033291714000531.CrossRefGoogle ScholarPubMed
Gage, S. H., Hickman, M., & Zammit, S. (2016). Association between cannabis and psychosis: Epidemiologic evidence. Biological Psychiatry, 79(7), 549–556. doi:10.1016/j.biopsych.2015.08.001.CrossRefGoogle ScholarPubMed
Gage, S. H., Jones, H. J., Burgess, S., Bowden, J., Davey Smith, G., Zammit, S., … Munafò, M. R. (2017). Assessing causality in associations between cannabis use and schizophrenia risk: A two-sample Mendelian randomization study. Psychological Medicine, 47(5), 971–980. doi:10.1017/S0033291716003172.CrossRefGoogle ScholarPubMed
Goodman, R. (1999). The extended version of the strengths and difficulties questionnaire as a guide to child psychiatric caseness and consequent burden. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 40(5), 791–799. doi:10.1017/S0021963099004096.CrossRefGoogle ScholarPubMed
Green, B., Young, R., & Kavanagh, D. (2005). Cannabis use and misuse prevalence among people with psychosis. British Journal of Psychiatry, 187, 306–313. doi:10.1192/bjp.187.4.306.CrossRefGoogle ScholarPubMed
Guloksuz, S., Pries, L. K., Delespaul, P., Kenis, G., Luykx, J. J., Lin, B. C. D., … van Os, J. (2019). Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: Results from the EUGEI study. World Psychiatry, 18(2), 173–182. doi:10.1002/wps.20629.CrossRefGoogle ScholarPubMed
Gurillo, P., Jauhar, S., Murray, R. M., & MacCabe, J. H. (2015). Does tobacco use cause psychosis? Systematic review and meta-analysis. The Lancet. Psychiatry, 2(8), 718–725. doi:10.1016/S2215-0366(15)00152-2.CrossRefGoogle ScholarPubMed
Handley, S. J., Capon, A., Beveridge, M., Dennis, I., & Evans, J. S. T. (2004). Working memory, inhibitory control and the development of children's reasoning. Thinking & Reasoning, 10(2), 175–195. doi:10.1080/13546780442000051.CrossRefGoogle Scholar
Heron, J. E., Croudace, T. J., Barker, E. D., & Tilling, K. (2015). A comparison of approaches for assessing covariate effects in latent class analysis. 6(4), 15. doi:10.14301/llcs.v6i4.322.Google Scholar
Horwood, J., Salvi, G., Thomas, K., Duffy, L., Gunnell, D., Hollis, C., … Harrison, G. (2008). IQ And non-clinical psychotic symptoms in 12-year-olds: Results from the ALSPAC birth cohort. British Journal of Psychiatry, 193, 185–191. doi:10.1192/bjp.bp.108.051904.CrossRefGoogle ScholarPubMed
Howe, L. J., Trela-Larsen, L., Taylor, M., Heron, J., Munafò, M. R., & Taylor, A. E. (2017). Body mass index, body dissatisfaction and adolescent smoking initiation. Drug and Alcohol Dependence, 178, 143–149. doi:10.1016/j.drugalcdep.2017.04.008.CrossRefGoogle ScholarPubMed
Hubbard, L., Tansey, K. E., Rai, D., Jones, P., Ripke, S., Chambert, K. D., … Zammit, S. (2016). Evidence of common genetic overlap between schizophrenia and cognition. Schizophrenia Bulletin, 42(3), 832–842. doi:10.1093/schbul/sbv168.CrossRefGoogle ScholarPubMed
Jones, H. J., Gage, S. H., Heron, J., Hickman, M., Lewis, G., Munafo, M. R., & Zammit, S. (2018). Association of combined patterns of tobacco and cannabis use in adolescence with psychotic experiences. JAMA Psychiatry, 75(3), 240–246. doi:10.1001/jamapsychiatry.2017.4271.CrossRefGoogle ScholarPubMed
Jones, H. J., Stergiakouli, E., Tansey, K. E., Hubbard, L., Heron, J., Cannon, M., … Zammit, S. (2016). Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population. JAMA Psychiatry, 73(3), 221–228. doi:10.1001/jamapsychiatry.2015.3058.CrossRefGoogle ScholarPubMed
Koob, G. F., & Volkow, N. D. (2016). Neurobiology of addiction: A neurocircuitry analysis. The Lancet. Psychiatry, 3(8), 760–773. doi:10.1016/S2215-0366(16)00104-8.CrossRefGoogle ScholarPubMed
Liu, M. Z., Jiang, Y., Wedow, R., Li, Y., Brazel, D. M., Chen, F., … Vrieze, S. (2019). Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. Nature Genetics, 51(2), 237–244. doi:10.1038/s41588-018-0307-5.CrossRefGoogle ScholarPubMed
Malmberg, A., Lewis, G., David, A., & Allebeck, P. (1998). Premorbid adjustment and personality in people with schizophrenia. British Journal of Psychiatry, 172, 308–313. doi:10.1192/bjp.172.4.308.CrossRefGoogle ScholarPubMed
Moore, T. H. M., Zammit, S., Lingford-Hughes, A., Barnes, T. R. E., Jones, P. B., Burke, M., & Lewis, G. (2007). Cannabis use and risk of psychotic or affective mental health outcomes: A systematic review. Lancet (London, England), 370(9584), 319–328. doi:10.1016/S0140-6736(07)61162-3.CrossRefGoogle ScholarPubMed
Muthén, L. K., & Muthén, B. O. (1998–2017). MPlus user's guide (8th ed.). Los Angeles, CA: Muthén & Muthén.Google Scholar
Pardiñas, A. F., Holmans, P., Pocklington, A. J., Escott-Price, V., Ripke, S., Carrera, N., … Walters, J. T. R. (2018). Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nature Genetics, 50(3), 381–389. doi:10.1038/s41588-018-0059-2.CrossRefGoogle ScholarPubMed
Pasman, J. A., Verweij, K. J. H., 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 influence of schizophrenia. Nature Neuroscience, 21(9), 1161–1170. doi:10.1038/s41593-018-0206-1.CrossRefGoogle Scholar
Power, R. A., Verweij, K. J. H., Zuhair, M., Montgomery, G. W., Henders, A. K., Heath, A. C., … Martin, N. G. (2014). Genetic predisposition to schizophrenia associated with increased use of cannabis. Molecular Psychiatry, 19(11), 1201–1204. doi:10.1038/mp.2014.51.CrossRefGoogle ScholarPubMed
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., … Sham, P. C. (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. American Journal of Human Genetics, 81, 559–575. doi:10.1086/519795.CrossRefGoogle ScholarPubMed
Purcell, S., Wray, N. R., Stone, J. L., Visscher, P. M., O'Donovan, M. C., & Sullivan, P. F., … International Schizophrenia Consortium (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 460, 748–752. doi:10.1038/nature08185.Google ScholarPubMed
Reginsson, G. W., Ingason, A., Euesden, J., Bjornsdottir, G., Olafsson, S., Sigurdsson, E., … Stefansson, K. (2017). Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction. Addiction Biology, 23(1), 485–492. doi:10.1111/adb.12496.CrossRefGoogle ScholarPubMed
Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., … Sullivan, P. F. (2013). Genome-wide association analysis identifies 14 new risk loci for schizophrenia. Nature Genetics, 45(10), 1150–1159. doi:10.1038/ng.2742.CrossRefGoogle Scholar
Saccone, N. L., Wang, J. C., Breslau, N., Johnson, E. O., Hatsukami, D., Saccone, S. F., … Bierut, L. J. (2009). The CHRNA5-CHRNA3-CHRNB4 nicotinic receptor subunit gene cluster affects risk for nicotine dependence in African-Americans and in European-Americans. Cancer Research, 69(17), 6848–6856. doi:10.1158/0008-5472.CAN-09-0786.CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511, 421–427. doi:10.1038/nature13595.CrossRefGoogle Scholar
Stringer, S., Minica, C. C., Verweij, K. J. H., Mbarek, H., Bernard, M., Derringer, J., … Vink, J. M. (2016). Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32330 subjects from the International Cannabis Consortium. Translational Psychiatry, 6, e769. doi:10.1038/tp.2016.36.CrossRefGoogle Scholar
Taylor, M., Collin, S. M., Munafò, M. R., MacLeod, J., Hickman, M., & Heron, J. (2017). Patterns of cannabis use during adolescence and their association with harmful substance use behaviour: Findings from a UK birth cohort. Journal of Epidemiology and Community Health, 71, 764–770. doi:10.1136/jech-2016-208503.CrossRefGoogle ScholarPubMed
Tobacco Genetics Consortium (2010). Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nature Genetics, 42(5), 441–447. doi:10.1038/ng.571.CrossRefGoogle Scholar
Valeri, L., & VanderWeele, T. J. (2013). Mediation analysis allowing for exposure-mediator interactions and causal interpretation: Theoretical assumptions and implementation with SAS and SPSS macros. Psychological Methods, 18(2), 137–150. doi:10.1037/a0031034.CrossRefGoogle ScholarPubMed
Varese, F., Smeets, F., Drukker, M., Lieverse, R., Lataster, T., Viechtbauer, W., … Bentall, R. P. (2012). Childhood adversities increase the risk of psychosis: A meta-analysis of patient-control, prospective- and cross-sectional cohort studies. Schizophrenia Bulletin, 38(4), 661–671. doi:10.1093/schbul/sbs050.CrossRefGoogle ScholarPubMed
Verweij, K. J. H., Abdellaoui, A., Nivard, M. G., Cort, A. S., Ligthart, L., Draisma, H. H. M., … Vink, J. M. (2017). Short communication: Genetic association between schizophrenia and cannabis use. Drug and Alcohol Dependence, 171, 117–121. doi:10.1016/j.drugalcdep.2016.09.022.CrossRefGoogle ScholarPubMed
Wechsler, D., Golombok, S., & Rust, J. (1992). Wechsler intelligence scale for children – third edition UK manual. Sidcup, UK: The Psychological Corporation.Google Scholar
Welham, J., Isohanni, M., Jones, P., & McGrath, J. (2009). The antecedents of schizophrenia: A review of birth cohort studies. Schizophrenia Bulletin, 35(3), 603–623. doi:10.1093/schbul/sbn084.CrossRefGoogle ScholarPubMed
Wolke, D., Woods, S., Bloomfield, L., & Karstadt, L. (2000). The association between direct and relational bullying and behaviour problems among primary school children. Journal of Child Psychology and Psychiatry, 41(8), 989–1002. doi:10.1017/S0021963099006381.CrossRefGoogle ScholarPubMed
Wootton, R. E., Richmond, R. C., Stuijfzand, B. G., Lawn, R. B., Sallis, H. M., Taylor, G. M. J., … Munafò, M. R. (2019). Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study. Psychological Medicine, 1–9. doi:10.1017/S0033291719002678.Google ScholarPubMed
Supplementary material: File

Jones et al. supplementary material

Jones et al. supplementary material

Download Jones et al. supplementary material(File)
File 252.4 KB