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Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not

Published online by Cambridge University Press:  02 October 2017

M. Aas*
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
I. Melle
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
F. Bettella
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
S. Djurovic
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
S. Le Hellard
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway
T. Bjella
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
P. A. Ringen
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
T. V. Lagerberg
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
O. B. Smeland
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
I. Agartz
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, Oslo, Norway Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
O. A. Andreassen
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
M. Tesli
Affiliation:
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway Department of Psychiatry, Lovisenberg Hospital, Oslo, Norway
*
*Address for correspondence: M. Aas, Ph.D., NORMENT KG Jebsen Psychosis Research Centre, Division of Mental Health and Addiction, Institute of Clinical Medicine, Bygg 49, Ullevål sykehus, PO Box 4956 Nydalen, 0424 Oslo, Norway. (Email: monica.aas@medisin.uio.no)

Abstract

Background

Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age <18 years) is believed to increase the risk of developing psychosis more than later use, follow-up analyses were conducted comparing early use to later use and no use.

Methods

We assigned a SZ-polygenic risk score (PGRS) to each individual in our independent sample (N = 381 SZ spectrum cases, 220 BD spectrum cases and 415 healthy controls), calculated from the results of the Psychiatric Genomics Consortium (PGC) SZ case–control study (N = 81 535). SZ-PGRS in patients who used cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis.

Results

Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset <18 years of age and patients with no or infrequent use of cannabis (p = 0.003, Cohen's d = 0.42).

Conclusions

Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2017 

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References

Agrawal, A, Lynskey, MT, Bucholz, KK, Kapoor, M, Almasy, L, Dick, DM, Edenberg, HJ, Foroud, T, Goate, A, Hancock, DB, Hartz, S, Johnson, EO, Hesselbrock, V, Kramer, JR, Kuperman, S, Nurnberger, JI Jr., Schuckit, M, Bierut, LJ (2014). DSM-5 cannabis use disorder: a phenotypic and genomic perspective. Drug Alcohol Dependence 134, 362369.CrossRefGoogle ScholarPubMed
Andreassen, OA, Thompson, WK, Schork, AJ, Ripke, S, Mattingsdal, M, Kelsoe, JR, Kendler, KS, O'Donovan, MC, Rujescu, D, Werge, T, Sklar, P, Roddey, JC, Chen, CH, McEvoy, L, Desikan, RS, Djurovic, S, Dale, AM (2013). Improved detection of common variants associated with schizophrenia and bipolar disorder using pleiotropy-informed conditional false discovery rate. PLoS Genetics 9, 4.CrossRefGoogle ScholarPubMed
Andreasson, S, Allebeck, P, Engstrom, A, Rydberg, U (1987). Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 2, 14831486.CrossRefGoogle ScholarPubMed
Arseneault, L, Cannon, M, Poulton, R, Murray, R, Caspi, A, Moffitt, TE (2002). Cannabis use in adolescence and risk for adult psychosis: longitudinal prospective study. BMJ 325, 12121213.CrossRefGoogle ScholarPubMed
Athanasiu, L, Mattingsdal, M, Kahler, AK, Brown, A, Gustafsson, O, Agartz, I, Giegling, I, Muglia, P, Cichon, S, Rietschel, M, Pietilainen, OP, Peltonen, L, Bramon, E, Collier, D, Clair, DS, Sigurdsson, E, Petursson, H, Rujescu, D, Melle, I, Steen, VM, Djurovic, S, Andreassen, OA (2010). Gene variants associated with schizophrenia in a Norwegian genome-wide study are replicated in a large European cohort. Journal of Psychiatric Research 44, 748753.CrossRefGoogle Scholar
Bigdeli, TB, Bacanu, SA, Webb, BT, Walsh, D, O'Neill, FA, Fanous, AH, Riley, BP, Kendler, KS (2014). Molecular validation of the schizophrenia spectrum. Schizophrenia Bulletin 40, 6065.CrossRefGoogle ScholarPubMed
Cohen, J (1977). Statistical Power Analysis for the Behavioral Sciences. Academic Press: New York.Google Scholar
Craddock, N, Owen, MJ (2010). The Kraepelinian dichotomy – going, going… but still not gone. British Journal of Psychiatry 196, 9295.CrossRefGoogle Scholar
Di Forti, M, Sallis, H, Allegri, F, Trotta, A, Ferraro, L, Stilo, SA, Marconi, A, La, CC, Reis, MT, Pariante, C, Dazzan, P, Mondelli, V, Paparelli, A, Kolliakou, A, Prata, D, Gaughran, F, David, AS, Morgan, C, Stahl, D, Khondoker, M, Maccabe, JH, Murray, RM (2014). Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users. Schizophrenia Bulletin 40, 15091517.CrossRefGoogle ScholarPubMed
Djurovic, S, Gustafsson, O, Mattingsdal, M, Athanasiu, L, Bjella, T, Tesli, M, Agartz, I, Lorentzen, S, Melle, I, Morken, G, Andreassen, OA (2010). A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample. Journal of Affective Disorder 126, 312316.CrossRefGoogle ScholarPubMed
Ferraro, L, Russo, M, O'Connor, J, Wiffen, BD, Falcone, MA, Sideli, L, Gardner-Sood, P, Stilo, S, Trotta, A, Dazzan, P, Mondelli, V, Taylor, H, Friedman, B, Sallis, H, La, CC, La, BD, David, AS, Reichenberg, A, Murray, RM, Di Forti, M (2013). Cannabis users have higher premorbid IQ than other patients with first onset psychosis. Schizophrenia Research 150, 129135.CrossRefGoogle ScholarPubMed
Finseth, PI, Sonderby, IE, Djurovic, S, Agartz, I, Malt, UF, Melle, I, Morken, G, Andreassen, OA, Vaaler, AE, Tesli, M (2014). Association analysis between suicidal behaviour and candidate genes of bipolar disorder and schizophrenia. Journal of Affective Disorder 163, 110114.CrossRefGoogle ScholarPubMed
Giusti-Rodriguez, P, Sullivan, PF (2013). The genomics of schizophrenia: update and implications. Journal of Clinical Investigation 123, 45574563.CrossRefGoogle ScholarPubMed
Grech, A, van, OJ, Jones, PB, Lewis, SW, Murray, RM (2005). Cannabis use and outcome of recent onset psychosis. European Psychiatry 20, 349353.CrossRefGoogle ScholarPubMed
Henquet, C, Krabbendam, L, de, GR, Ten, HM, van, OsJ (2006). Cannabis use and expression of mania in the general population. Journal of Affective Disorder 95, 103110.CrossRefGoogle ScholarPubMed
Home Office Research Development and Statistics Directorate BMRB (2008). British Crime Survey, 2007–2008. Home Office: London.Google Scholar
Iyegbe, C, Campbell, D, Butler, A, Ajnakina, O, Sham, P (2014). The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for G × E research. Social Psychiatry and Psychiatric Epidemiology 49, 169182.CrossRefGoogle Scholar
Kendler, KS, Ohlsson, H, Maes, HH, Sundquist, K, Lichtenstein, P, Sundquist, J (2015). A population-based Swedish Twin and Sibling Study of cannabis, stimulant and sedative abuse in men. Drug Alcohol Dependence 149, 4954.CrossRefGoogle ScholarPubMed
Kirkbride, JB, Fearon, P, Morgan, C, Dazzan, P, Morgan, K, Murray, RM, Jones, PB (2007). Neighbourhood variation in the incidence of psychotic disorders in Southeast London. Social Psychiatry and Psychiatric Epidemiology 42, 438445.CrossRefGoogle ScholarPubMed
Kirkbride, JB, Fearon, P, Morgan, C, Dazzan, P, Morgan, K, Tarrant, J, Lloyd, T, Holloway, J, Hutchinson, G, Leff, JP, Mallett, RM, Harrison, GL, Murray, RM, Jones, PB (2006). Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP study. Archives of General Psychiatry 63, 250258.CrossRefGoogle ScholarPubMed
Lagerberg, TV, Kvitland, LR, Aminoff, SR, Aas, M, Ringen, PA, Andreassen, OA, Melle, I (2014). Indications of a dose-response relationship between cannabis use and age at onset in bipolar disorder. Psychiatry Research 215, 101104.CrossRefGoogle ScholarPubMed
Loberg, EM, Helle, S, Nygard, M, Berle, JO, Kroken, RA, Johnsen, E (2014). The cannabis pathway to non-affective psychosis may reflect less neurobiological vulnerability. Frontiers in Psychiatry 5, 159.Google ScholarPubMed
Lynskey, MT, Agrawal, A, Henders, A, Nelson, EC, Madden, PA, Martin, NG (2012). An Australian twin study of cannabis and other illicit drug use and misuse, and other psychopathology. Twin Research and Human Genetics 15, 631641.CrossRefGoogle ScholarPubMed
Marconi, A, Di Forti, M, Lewis, CM, Murray, RM, Vassos, E (2016). Meta-analysis of the association between the level of cannabis use and risk of psychosis. Schizophrenia Bulletin 42, 12621269.CrossRefGoogle ScholarPubMed
McGrath, J, Saha, S, Chant, D, Welham, J (2008). Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews 30, 6776.CrossRefGoogle ScholarPubMed
Power, RA, Verweij, KJ, Zuhair, M, Montgomery, GW, Henders, AK, Heath, AC, Madden, PA, Medland, SE, Wray, NR, Martin, NG (2014). Genetic predisposition to schizophrenia associated with increased use of cannabis. Molecular Psychiatry 19, 12011204.CrossRefGoogle ScholarPubMed
Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, Sklar, P (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748752.Google ScholarPubMed
Ringen, PA, Lagerberg, TV, Birkenaes, AB, Engn, J, Faerden, A, Jonsdottir, H, Nesvag, R, Friis, S, Opjordsmoen, S, Larsen, F, Melle, I, Andreassen, OA (2008 a). Differences in prevalence and patterns of substance use in schizophrenia and bipolar disorder. Psychological Medicine 38, 12411249.CrossRefGoogle ScholarPubMed
Ringen, PA, Melle, I, Birkenaes, AB, Engh, JA, Faerden, A, Jonsdottir, H, Nesvag, R, Vaskinn, A, Friis, S, Larsen, F, Opjordsmoen, S, Sundet, K, Andreassen, OA (2008 b). Illicit drug use in patients with psychotic disorders compared with that in the general population: a cross-sectional study. Acta Psychiatrica Scandinavica 117, 133138.CrossRefGoogle ScholarPubMed
Ringen, PA, Nesvag, R, Helle, S, Lagerberg, TV, Lange, EH, Loberg, EM, Agartz, I, Andreassen, OA, Melle, I (2016). Premorbid cannabis use is associated with more symptoms and poorer functioning in schizophrenia spectrum disorder. Psychological Medicine 46, 31273136.CrossRefGoogle ScholarPubMed
Rosenthal, R, Rosnow, RLR (1984). Essentials of Behavioural Research: Methods and Data Analysis. McGraw-Hill: New York, NY.Google Scholar
Sherva, R, Wang, Q, Kranzler, H, Zhao, H, Koesterer, R, Herman, A, Farrer, LA, Gelernter, J (2016). Genome-wide association study of cannabis dependence severity, novel risk variants, and shared genetic risks. JAMA Psychiatry 73, 472480.CrossRefGoogle ScholarPubMed
Smoller, JW, Finn, CT (2003). Family, twin, and adoption studies of bipolar disorder. American Journal of Medical Genetics 123C, 4858.Google ScholarPubMed
Tesli, M, Espeseth, T, Bettella, F, Mattingsdal, M, Aas, M, Melle, I, Djurovic, S, Andreassen, OA (2014). Polygenic risk score and the psychosis continuum model. Acta Psychiatrica Scandinavica 130, 311317.CrossRefGoogle ScholarPubMed
Van Winkel, R, Kuepper, R (2014). Epidemiological, neurobiological, and genetic clues to the mechanisms linking cannabis use to risk for nonaffective psychosis. The Annual Review of Clinical Psychology 10, 767791.CrossRefGoogle Scholar
Verweij, KJ, Abdellaoui, A, Nivard, MG, Sainz Cort, A, Ligthart, L, Draisma, HH, Minica, CC (2017). Short communication: genetic association between schizophrenia and cannabis use. Drug Alcohol Depend 171, 117121.CrossRefGoogle ScholarPubMed
Word Health Organisation (2016). The health and social effects of nonmedical cannabis use. ISBN: 978 924 1510240.Google Scholar
Zammit, S, Allebeck, P, Andreasson, S, Lundberg, I, Lewis, G (2002). Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. BMJ 325, 1199.CrossRefGoogle ScholarPubMed
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