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      The contribution of cannabis use to variation in the incidence of psychotic disorder across Europe (EU-GEI): a multicentre case-control study

      research-article
      , PhD a , e , f , * , , MD a , e , f , , PhD g , , MSc c , , PhD d , , MD c , , MD c , , PhD h , t , , PhD i , , PhD i , , Prof, MD i , , PhD j , , Prof, MD j , , Prof, PhD k ,   , Prof, PhD l , , PhD m , , PhD n , , Prof, PhD o , , PhD p , , Prof, PhD q , , Prof, PhD r , , Prof, PhD h , s , , PhD t , , Prof, PhD u , , Prof, PhD n , , Prof, PhD a , v , , Prof, PhD c , w , , Prof, PhD a , e , , Prof, PhD b , , Prof, PhD d , , Prof, FRS c , f , EU-GEI WP2 Group
      The Lancet. Psychiatry
      Elsevier

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          Summary

          Background

          Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder.

          Methods

          We included patients aged 18–64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ 9-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites.

          Findings

          Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3·2, 95% CI 2·2–4·1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4·8, 2·5–6·3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12·2% (95% CI 3·0–16·1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30·3% (15·2–40·0) in London and 50·3% (27·4–66·0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0·7; p=0·0286) and daily use (r = 0·8; p=0·0109).

          Interpretation

          Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.

          Funding source

          Medical Research Council, the European Community's Seventh Framework Program grant, São Paulo Research Foundation, National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR BRC at University College London, Wellcome Trust.

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          Most cited references36

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          Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review.

          Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.
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            A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system.

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              • Article: not found

              Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis.

              Cannabis use has been reported to induce long-lasting psychotic disorders and a dose-response relationship has been observed. We performed a systematic review of studies that investigate the association between the degree of cannabis consumption and psychosis and a meta-analysis to quantify the magnitude of effect. Published studies were identified through search of electronic databases, supplemented by manual searches of bibliographies. Studies were considered if they provided data on cannabis consumption prior to the onset of psychosis using a dose criterion (frequency/amount used) and reported psychosis-related outcomes. We performed random effects meta-analysis of individual data points generated with a simulation method from the summary data of the original studies. From 571 references, 18 studies fulfilled inclusion criteria for the systematic review and 10 were inserted in the meta-analysis, enrolling a total of 66 816 individuals. Higher levels of cannabis use were associated with increased risk for psychosis in all the included studies. A logistic regression model gave an OR of 3.90 (95% CI 2.84 to 5.34) for the risk of schizophrenia and other psychosis-related outcomes among the heaviest cannabis users compared to the nonusers. Current evidence shows that high levels of cannabis use increase the risk of psychotic outcomes and confirms a dose-response relationship between the level of use and the risk for psychosis. Although a causal link cannot be unequivocally established, there is sufficient evidence to justify harm reduction prevention programs.
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                Author and article information

                Contributors
                Journal
                Lancet Psychiatry
                Lancet Psychiatry
                The Lancet. Psychiatry
                Elsevier
                2215-0366
                2215-0374
                1 May 2019
                May 2019
                : 6
                : 5
                : 427-436
                Affiliations
                [a ]Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
                [b ]Department of Addiction, Institute of Psychiatry, King's College London, London, UK
                [c ]Institute of Psychiatry, Psychology and Neuroscience and Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK
                [d ]Department of Health Service and Population Research, Institute of Psychiatry, King's College London, London, UK
                [e ]National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, UK
                [f ]South London and Maudsley NHS Mental Health Foundation Trust, London, UK
                [g ]Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK
                [h ]Department of Psychiatry, University of Cambridge, Cambridge, UK
                [i ]Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy
                [j ]Department of Medical and Surgical Science, Psychiatry Unit, Alma Mater Studiorum Università di Bologna, Bologna, Italy
                [k ]INSERM U955, Equipe 15, Institut National de la Santé et de la Recherche Médicale, Créteil, Paris, France
                [l ]Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM (CIBERSAM), Madrid, Spain
                [m ]Etablissement Public de Santé Maison Blanche, Paris, France
                [n ]Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands
                [o ]Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital clinic, Department of Medicine, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
                [p ]Division of Psychiatry, Department of Neuroscience and Behaviour, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
                [q ]Department of Preventative Medicine, Faculdade de Medicina FMUSP, University of São Paulo, São Paulo, Brazil
                [r ]Rivierduinen Institute for Mental Health Care, Leiden, Netherlands
                [s ]CAMEO Early Intervention Service, Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK
                [t ]Psylife Group, Division of Psychiatry, University College London, London, UK
                [u ]Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, Maastricht, Netherlands
                [v ]Centre for Genomic Sciences, Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
                [w ]Brain Centre Rudolf Magnus, Utrecht University Medical Centre, Utrecht, The Netherlands
                Author notes
                [* ]Correspondence to: Dr Marta Di Forti, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK marta.diforti@ 123456kcl.ac.uk
                [†]

                Collaborators listed in the appendix

                Article
                S2215-0366(19)30048-3
                10.1016/S2215-0366(19)30048-3
                7646282
                30902669
                d0641ef2-bc48-43af-bd3b-10a3176f25d1
                © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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