Results Case-control studies Chen et al 2003;

1. ‘Can one predict who will develop a Mephedrone-induced Psychosis?’:A systematic literature review of individual factors modulating risk of developing amphetamine-psychosis.  Katherine Adlington and Robin M. Murray Final Year Medical Student, King’s College London UK; Professor of Psychiatric Research, Institute of Psychiatry, UK • Results • Case-control studies • Chen et al 2003; • Premorbid Schizoid/Schizotypal Personality Traits increases risk of developing methamphetamine-induced psychosis • Genetic Association studies • 1 high quality; 8 medium quality; 6 low quality papers • Investigating associations in 19 different genes with a variety of functions: • Significant association with methamphetamine-psychosis was shown in following studies: • 1 high quality (gene= G72; odds ratio = 1.62) • 4 medium quality (DRD2, GRM2, HTTLPR, MAOA) • 2 low quality (ESR1, HTR1A) • Highest odds ratio for gene DRD2 = 3.62 • Conclusion • The Systematic Literature Review identified a number of innate risk factors that appear to increase individual vulnerability to methamphetamine-psychosis:- • Behavioural markers • (premorbid schizoid personality traits & childhood attentional dysfunction) • Reflects early cognitive vulnerability • Family history of psychosis & psychiatric illness • Strong evidence of an inherited susceptibility • Tentative evidence of underlying risk genes • 15 studies in past 2 years showing 7 genes associated with amphetamine-psychosis • Each gene has a small relative effect size • Probably reflects a polygenic susceptibility conferred by multiple genes with small effect • Limitations • Lack of formal studies of mephedrone • Recall bias in case-control studies • Small sample sizes in GA studies • Acceptable to extrapolate results from methamphetamine studies to predict mephedrone risk? • Background • Anecdotal reports associating mephedrone with onset of acute psychotic symptoms (Psychonaut 2009) • No studies investigating long term psychosis risk • Chemical & effectual similarity with amphetamines • Well established psychosis risk associated with amphetamines (Connell 1958) • Recent studies show chronic methamphetamine use leads to paranoid-hallucinatory states indistinguishable from paranoid schizophrenia (Chen, Lin et al 2003) • Variability exists in onset and prognosis of methamphetamine-induced psychosis suggests there is a spectrum of pre-existing vulnerability to the condition • Method • Systematic literature search: • Recent experimental & observational studies in humans taking amphetamine-like recreational drugs investigating non-environmental risk factors for developing psychosis following substance use • Literature search 2003 - present: a) Medline/Pubmed b) Psychinfo c)Google scholar Search terms (combination 1 ∩ 2 ∩ 3) • Search Criteria: English language papers; exploring innate risk factors; empirical research; human subjects • Check all references & citations Quality Assessment • Quality limited by involvement of drugs of abuse - RCTs ethically not possible • Exclusion criteria = Case reports; neuroimaging studies; articles in past SLRs • High or low quality scores awarded based on criteria: • 2 criteria = high quality; 1 criterion = medium quality; 0 criteria = low quality • Recent emergence of substituted cathinone ‘legal highs’ • 2009 - 4-methylmethcathinone, ‘mephedrone’ = 4th most popular club drug (Mixmag 2010) • Chen et al 2005; • Meth-users with family history of schizophrenia at increased risk of psychosis • Greater familial loading the more prolonged the psychosis Cathinone ‘Khat’ 4MMC ‘Mephedrone’ Methamphetamine Amphetamine 3) Salo et al 2008; • Family history of psychiatric illness & • Childhood attentional dysfunction • Both associated with increased risk of meth-induced psychosis Take home message By extrapolation from the recent research into risk factors for amphetamine-induced psychosis, this systematic literature review suggests: Mephedrone use may lead to an amphetamine-like psychosis &; Family hx of psychosis, genetic & pre-existing cognitive traits may be used as markers to predict who will develop a Mephedrone-induced psychosis. Fig. 1. Correlation between frequency of methamphetamine-induced psychotic episodes and self-reported UTAH ratings of childhood attention in 39 meth-dependent individuals. (r=0.56, p=0.0002) • Objective • Explore the factors that modulate individual risk of psychosis in amphetamine-users as reported in recent literature • Focus on family risk and both behavioural and molecular genetic factors No. studies Search Results 4 high quality Literature cited Chen CK, Lin SK et al. (2005). Am J Med Gene B NeuropsychiGenet.136B(1):87-91. Chen CK, Lin SK, et al (2003) Psychol Med. 2003 Nov;33(8):1407-14. Connell, P.H. (1958) Amphetamine Psychosis . London. Oxford University Press Mixmag (2010) “The Mixmag Drug Survey” 44-53 Psychonaut (2009) Mephedrone Report Psychonaut web mapping research group. Salo, R. et al (2008) Psychiatry Research 157; 273 All other citations available from the author – katherine.adlington@kcl.ac.uk Original search: 146 papers found 41 fulfill search criteria 18 fulfill quality assessment 8 medium quality 6 low quality Final papers • 3 retrospective, observational case-control studies • 14 genetic association studies • All studies involve methamphetamine