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

TY - JOUR

T1 - Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not

AU - Aas, M.

AU - Melle, I.

AU - Bettella, F.

AU - Djurovic, S.

AU - Le Hellard, S.

AU - Bjella, T.

AU - Ringen, P. A.

AU - Lagerberg, T. V.

AU - Smeland, O. B.

AU - Agartz, I.

AU - Andreassen, O. A.

AU - Tesli, M.

N1 - Funding Information: This study was funded by grants from the University of Oslo, South-Eastern Norway Health Authority (#2013088) and the Research Council of Norway and the KG Jebsen Foundation. Publisher Copyright: © 2017 Cambridge University Press.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Bipolar disorders

KW - cannabis

KW - polygenic risk score

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85030848830&partnerID=8YFLogxK

U2 - 10.1017/S0033291717001209

DO - 10.1017/S0033291717001209

M3 - Article

C2 - 28967348

AN - SCOPUS:85030848830

SN - 0033-2917

VL - 48

SP - 43

EP - 49

JO - Psychological Medicine

JF - Psychological Medicine

IS - 1

ER -