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Results
Case-control studies
1) 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
Katherine Adlington and Robin M. Murray Final Year Medical Student, King’s College London UK; Professor of Psychiatric Research, Institute of Psychiatry, UK
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
‘Can one predict who will develop a Mephedrone-induced Psychosis?’:A systematic literature review of individual factors modulating risk of developing amphetamine-psychosis.

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
Cathinone ‘Khat’ 4MMC ‘Mephedrone’
Amphetamine Methamphetamine
Recent emergence of substituted cathinone ‘legal highs’
2009 - 4-methylmethcathinone, ‘mephedrone’ = 4th most popular club drug (Mixmag 2010)
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)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
1 2 3
methamphetamineamphetamine
psychosis, schizophrenia
risk factors, susceptibility, inherited risk, genetic risk, personality traits, family risk, family history, psychiatric history
Case-control studies
Amphetamine users with psychosis compared to amphetamine users without psychosis
Non-environmental risk factors for psychosis identified & associations measured
Genetic studies
Reports odds rations, confidence intervals & power>0.9
Reports ORs, CIs & power>0.8
Search ResultsOriginal search: 146 papers found
41 fulfill search criteria
18 fulfill quality assessment
4 high quality
6 low qualityFinal papers 3 retrospective, observational case-control studies 14 genetic association studies
All studies involve methamphetamine
2)Chen et al 2005; Meth-users with family
history of schizophrenia at increased risk of psychosis
Greater familial loading the more prolonged the psychosis
3) Salo et al 2008;Family history of psychiatric illness &Childhood attentional dysfunction
Both associated with increased risk of meth-induced psychosis
8 medium quality
0
1
2
3
4
ACh
Dopamine
Glutam
ateG
lutamine
Glutatione
NMDA
Oestrogen
Other
Serotonin
Target gene signalling function
Study
Associatedgene
Conclusion
The Systematic Literature Review identified a number of innate risk factors that appear to increase individual vulnerability to methamphetamine-psychosis:-
1) Behavioural markers (premorbid schizoid personality traits & childhood
attentional dysfunction) Reflects early cognitive vulnerability
2) Family history of psychosis & psychiatric illness Strong evidence of an inherited susceptibility
3) 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?
Take home messageBy extrapolation from the recent research into risk factors for amphetamine-induced psychosis, this systematic literature review suggests:1.Mephedrone use may lead to an amphetamine-like psychosis &;2.Family hx of psychosis, genetic & pre-existing cognitive traits may be used as markers to predict who will develop a Mephedrone-induced psychosis.
Literature citedChen 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 PressMixmag (2010) “The Mixmag Drug Survey” 44-53Psychonaut (2009) Mephedrone Report Psychonaut web mapping research group. Salo, R. et al (2008) Psychiatry Research 157; 273
All other citations available from the author – [email protected]
No. studies
Fig. 1. Correlation between frequency of methamphetamine-inducedpsychotic episodes and self-reported UTAH ratings of childhood attention in 39 meth-dependent individuals. (r=0.56, p=0.0002)
