title: Interaction Between Functional Genetic Variation of DRD2 and Cannabis Use on Risk of Psychosis.
abstract: Both cannabis use and the dopamine receptor (DRD2) gene have been associated with schizophrenia, psychosis-like experiences, and cognition. However, there are no published data investigating whether genetically determined variation in DRD2 dopaminergic signaling might play a role in individual susceptibility to cannabis-associated psychosis. We genotyped (1) a case-control study of 272 patients with their first episode of psychosis and 234 controls, and also from (2) a sample of 252 healthy subjects, for functional variation in DRD2, rs1076560. Data on history of cannabis use were collected on all the studied subjects by administering the Cannabis Experience Questionnaire. In the healthy subjects' sample, we also collected data on schizotypy and cognitive performance using the Schizotypal Personality Questionnaire and the N-back working memory task. In the case-control study, we found a significant interaction between the rs1076560 DRD2 genotype and cannabis use in influencing the likelihood of a psychotic disorder. Among cannabis users, carriers of the DRD2, rs1076560, T allele showed a 3-fold increased probability to suffer a psychotic disorder compared with GG carriers (OR = 3.07; 95% confidence interval [CI]: 1.22-7.63). Among daily users, T carrying subjects showed a 5-fold increase in the odds of psychosis compared to GG carriers (OR = 4.82; 95% CI: 1.39-16.71). Among the healthy subjects, T carrying cannabis users had increased schizotypy compared with T carrying cannabis-naïve subjects, GG cannabis users, and GG cannabis-naïve subjects (all P ≤ .025). T carrying cannabis users had reduced working memory accuracy compared with the other groups (all P ≤ .008). Thus, variation of the DRD2, rs1076560, genotype may modulate the psychosis-inducing effect of cannabis use.
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Marco
authors.initials: M
authors.lastname: Colizzi
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Conrad
authors.initials: C
authors.lastname: Iyegbe
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MA;
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ursini
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy;
authors.forename: Annamaria
authors.initials: A
authors.lastname: Porcelli
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy;
authors.forename: Aurora
authors.initials: A
authors.lastname: Bonvino
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy;
authors.forename: Paolo
authors.initials: P
authors.lastname: Taurisano
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy;
authors.forename: Raffaella
authors.initials: R
authors.lastname: Romano
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy;
authors.forename: Rita
authors.initials: R
authors.lastname: Masellis
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy;
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Blasi
authors.affiliation: Department of Health Services and Population Research, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Craig
authors.initials: C
authors.lastname: Morgan
authors.affiliation: MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Katherine
authors.initials: K
authors.lastname: Aitchison
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: Department of Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Sonija
authors.initials: S
authors.lastname: Luzi
authors.affiliation: National Institute for Health Research Maudsley Biomedical Research Centre and Dementia Unit, London, UK;
authors.forename: Anna
authors.initials: A
authors.lastname: Kolliakou
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Anthony
authors.initials: A
authors.lastname: David
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK;
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro," Bari, Italy; pRED, NORD DTA, F. Hoffman-La Roche Ltd., Basel, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolino
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; marta.diforti@kcl.ac.uk.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Forti
mesh_terms: D000293:Adolescent; D000328:Adult; D002188:Cannabis / Q000009:adverse effects*; D016022:Case-Control Studies; D004198:Disease Susceptibility; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D011605:Psychoses, Substance-Induced / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012306:Risk; D012559:Schizophrenia / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000235:genetics*; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2
keywords: G × E interaction; dopamine receptors type 2; schizophrenia; schizotypy; working memory.
references.citation: Arch Gen Psychiatry. 2001 Oct;58(10):909-15
references.pmid: 11576028
references.citation: Biol Psychiatry. 2005 Mar 15;57(6):688-91
references.pmid: 15780858
references.citation: Q J Nucl Med. 1998 Sep;42(3):211-21
references.pmid: 9796369
references.citation: Lancet. 2007 Jul 28;370(9584):319-28
references.pmid: 17662880
references.citation: Nat Rev Neurosci. 2008 Sep;9(9):696-709
references.pmid: 18714326
references.citation: Curr Opin Psychiatry. 2008 Mar;21(2):140-50
references.pmid: 18332661
references.citation: Mol Psychiatry. 2000 May;5(3):270-4
references.pmid: 10889529
references.citation: Schizophr Bull. 2014 Nov;40(6):1509-17
references.pmid: 24345517
references.citation: Schizophr Res. 2013 Oct;150(1):129-35
references.pmid: 23958486
references.citation: Drug Alcohol Depend. 1998 Jun-Jul;51(1-2):49-60
references.pmid: 9716929
references.citation: Am J Psychiatry. 2011 Oct;168(10):1041-9
references.pmid: 21890791
references.citation: Psychol Bull. 1999 Jan;125(1):155-64
references.pmid: 9990848
references.citation: Nature. 2014 Jul 24;511(7510):421-7
references.pmid: 25056061
references.citation: Dev Neurosci. 1998;20(2-3):188-203
references.pmid: 9691193
references.citation: Biol Psychiatry. 2011 Jun 15;69(12):e127-43
references.pmid: 21397212
references.citation: Neurology. 2002 Nov 12;59(9):1337-43
references.pmid: 12427880
references.citation: Am J Psychiatry. 1999 Feb;156(2):286-93
references.pmid: 9989565
references.citation: Psychopharmacology (Berl). 2009 Jul;205(1):45-52
references.pmid: 19326102
references.citation: Psychopharmacology (Berl). 2002 Jun;161(4):331-9
references.pmid: 12073159
references.citation: Arch Gen Psychiatry. 2011 Feb;68(2):148-57
references.pmid: 21041608
references.citation: Psychiatry Res. 2011 Mar 30;186(1):46-52
references.pmid: 20813412
references.citation: Int Rev Psychiatry. 2009 Apr;21(2):152-62
references.pmid: 19367509
references.citation: Neuropsychopharmacology. 2011 Nov;36(12):2529-37
references.pmid: 21775978
references.citation: PLoS One. 2010;5(2):e9348
references.pmid: 20179754
references.citation: Nature. 2010 Nov 11;468(7321):203-12
references.pmid: 21068828
references.citation: Biol Psychiatry. 2013 Jul 15;74(2):106-12
references.pmid: 23312565
references.citation: Schizophr Res. 2011 Apr;127(1-3):22-7
references.pmid: 21310591
references.citation: Br J Addict. 1991 Sep;86(9):1119-27
references.pmid: 1932883
references.citation: Lancet. 2014 May 10;383(9929):1677-87
references.pmid: 24315522
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20552-7
references.pmid: 18077373
references.citation: J Psychiatr Res. 1999 Nov-Dec;33(6):543-8
references.pmid: 10628531
references.citation: JAMA. 2002 Mar 6;287(9):1123-31
references.pmid: 11879109
references.citation: Minn Med. 2007 Jan;90(1):36-8
references.pmid: 17305103
references.citation: Schizophr Res. 2007 May;92(1-3):74-84
references.pmid: 17379482
references.citation: Biol Psychiatry. 2014 Mar 15;75(6):430-1
references.pmid: 24560431
references.citation: Neuropsychopharmacology. 2015 Feb;40(3):640-9
references.pmid: 25139064
references.citation: Front Behav Neurosci. 2014 Jul 09;8:235
references.pmid: 25071490
references.citation: Nat Med. 2012 Feb;18(2):211-3
references.pmid: 22310688
references.citation: Neuropsychopharmacology. 2006 Dec;31(12):2748-57
references.pmid: 16936704
references.citation: Arch Gen Psychiatry. 2009 Jan;66(1):13-20
references.pmid: 19124684
references.citation: Br J Psychiatry. 2009 Dec;195(6):488-91
references.pmid: 19949195
references.citation: Nature. 2000 Nov 9;408(6809):199-203
references.pmid: 11089973
references.citation: Nat Rev Neurosci. 2007 Nov;8(11):885-95
references.pmid: 17925811
references.citation: Epidemiol Psichiatr Soc. 2005 Oct-Dec;14(4):184-7
references.pmid: 16396425
references.citation: Brain. 2009 Feb;132(Pt 2):417-25
references.pmid: 18829695
references.citation: Br J Psychiatry. 2011 Nov;199(5):380-5
references.pmid: 21947654
references.citation: Schizophr Bull. 2009 May;35(3):549-62
references.pmid: 19325164
references.citation: Neuropsychopharmacology. 2004 Aug;29(8):1558-72
references.pmid: 15173844
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2007 Jun 30;31(5):1054-63
references.pmid: 17482741
references.citation: Soc Psychiatry Psychiatr Epidemiol. 2002 Jul;37(7):329-35
references.pmid: 12111025
references.citation: Schizophr Bull. 2008 Nov;34(6):1066-82
references.pmid: 18791076
references.citation: Alcohol Clin Exp Res. 1993 Dec;17(6):1188-92
references.pmid: 8116829
references.citation: J Abnorm Psychol. 1994 May;103(2):171-83
references.pmid: 8040487
references.citation: Neuropharmacology. 2004;47 Suppl 1:3-13
references.pmid: 15464121
references.citation: Biol Psychiatry. 2014 Mar 15;75(6):470-8
references.pmid: 23820822
references.citation: Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1158-63
references.pmid: 21187413
references.citation: J Neurosci. 2009 Nov 25;29(47):14812-9
references.pmid: 19940176
references.citation: JAMA Psychiatry. 2013 Sep;70(9):921-30
references.pmid: 23842608
references.citation: Schizophr Bull. 2005 Jul;31(3):608-12
references.pmid: 15976013
references.citation: Biol Psychiatry. 2012 Nov 15;72(10):811-6
references.pmid: 22831980
references.citation: Eur Arch Psychiatry Clin Neurosci. 2009 Oct;259(7):413-31
references.pmid: 19609589
references.citation: Psychol Med. 2008 Sep;38(9):1257-66
references.pmid: 18005495
references.citation: Schizophr Bull. 1991;17(4):555-64
references.pmid: 1805349
references.citation: Biol Psychiatry. 2005 May 15;57(10):1117-27
references.pmid: 15866551
references.citation: Neuropsychopharmacology. 2013 Jul;38(8):1598-606
references.pmid: 23449176
references.citation: Neurosci Lett. 1997 May 2;226(3):159-62
references.pmid: 9175591