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. 2023 Jul:325:115249.
doi: 10.1016/j.psychres.2023.115249. Epub 2023 May 9.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort

Alex G Segura  1 , Anna Mané  2 , Llucia Prohens  1 , Natalia Rodriguez  1 , Gisela Mezquida  3 , Manuel J Cuesta  4 , Eduard Vieta  5 , Silvia Amoretti  6 , Antonio Lobo  7 , Ana González-Pinto  8 , Covadonga M Diaz-Caneja  9 , Alexandra Roldán Bejarano  10 , Esther Jimenez  5 , Immaculada Baeza  11 , Teresa Legido  12 , Jeronimo Saiz-Ruiz  13 , Miguel Bernardo  14 , Sergi Mas  15 ; PEPs Group
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Free article

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort

Alex G Segura et al. Psychiatry Res. 2023 Jul.
Free article

Abstract

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP. A cohort of 249 FEP individuals were evaluated during 12 months. Symptom severity was measured with the Positive and Negative Severity Scale and cannabis use with the EuropASI scale. Individual PRS for lifetime cannabis initiation (PRSCI) and cannabis use disorder (PRSCUD) were constructed. Current cannabis use was associated with increased positive symptoms. Cannabis initiation at younger ages conditioned the 12-month symptom progression. FEP patients with higher cannabis PRSCUD reported increased baseline cannabis use. PRSCI was associated with the course of negative and general symptomatology over follow-up. Cannabis use and symptom progression after a FEP were modulated by cannabis PRS, suggesting that lifetime initiation and use disorders may have partially independent genetic factors. These exploratory results may be the first step to identify those FEP patients more vulnerable to cannabis use and worse outcomes to ultimately develop tailored treatments.

Keywords: Cannabis; Genetics; Polygenic risk score; Psychosis; Schizophrenia.

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Conflict of interest statement

Declaration of Competing Interest C. De-la-Camara received financial support to attend scientific meetings from Janssen-Cilag, Almirall, Eli Lilly, Lundbeck, Rovi, Esteve, Novartis, and Astrazeneca. E. Vieta has received grants and/or acted as consultant and/or speaker for the following companies: AB-Biotics, Abbott, Allergan, Angelini, Astra-Zeneca, Dainippon Sumitomo, Ferrer, Janssen, Lundbeck, Novartis, Otsuka, Pfizer, Richter, Sage, Sanofi, Servier, Sunovion, and Takeda. A. Gonzalez-Pinto has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Sanofi-Aventis, Exeltis, Angelini, the Spanish Ministry of Science and Innovation (CIBERSAM), and the Basque Government. M. Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka, Takeda, Somatics and has obtained research funding from the Ministry of Education, Culture and Sport, the Spanish Ministry of Economy, Industry and Competitiveness (CIBERSAM), by the Government of Catalonia, Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017SGR1355), Foundation European Group for Research In Schizophrenia (EGRIS), and the 7th Framework Program of the European Union. M. Bioque has received honoraria from talks and consultancy of Adamed, has received honoraria from consultancy of Ferrer, has received research support and honoraria from talks and consultancy of Janssen-Cilag, has received honoraria from talks and consultancy of Lundbeck, has received honoraria from talks and consultancy of Otsuka, and a research prize from Pfizer M. Gutierrez has been on the speakers/advisory board of Janssen-Cilag. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/ BMD-2422 AGES; S2017/BMD-3740), JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis. S. Amoretti has been supported by a Sara Borrell contract (CD20/00177), funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Social Fund "Investing in your future”. Anna Mané has received funds from Otsuka and Angelini as a speaker and for congress registration and travel expenses. The other authors declare no conflict of interest.

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