Sz and experimental medicine

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  • Proteomics: cytoskeleton, glc metabolism, Ca channel signalling in PFCl & anterior temporal structures [D1, D2, gluR], oligodendrocytes [neurodegeneration]
  • Tolerability of outpatient antipsychotic treatment: 36-month results from the European Schizophrenia Outpatient Health Outcomes (SOHO) study. Source: European neuropsychopharmacology [0924-977X] Novick, Diego yr:2009 vol:19 iss:8 pg:542 -550
  • Possibly also melanocortin 4, insulin & leptingenes; evidence changes in islet cells in vitro, insulin metabolism in FEPMain message seems to be need better informatics, methodology, GxE
  • proteomics
  • NEWMEDS modafinilCognition enhancers: e.g. Nicotinc alpha7 agonists, H3 agonists
  • Face, UCLA data
  • RABIES
  • Sz and experimental medicine

    1. 1. Experimental medicine: Schizophrenia Update Richard Drake Institute of Brain, Behaviour & Mental Health
    2. 2. Understanding processes• Pharmacogenomics – Predictors of prognosis – Predictors of response• Proteomics, PET – Markers of relapse or response – Identify key processes – Predict outcomes Martins-de-Souza D., et al. Expert Rev Proteomics. 2012;9(1):97-108
    3. 3. Novick D et al (2009)Eur Neuropsychopharmacol 19 (8);542-50
    4. 4. APS Weight gain• h2 40-70%• Worse if 5HT2c wild-type (cf MC4R) – Han Chinese & Spanish (also UK haplotype) – CPZ, RSP; OLZ, misc. APS Foley DL & Morely KI (2011) Arch Gen Psych epub 7.2.11• Metformin RCTs have mixed results• 750-1000mg/d efficacious in earlier illness, weight gain group, Chinese• May normalise menstruation Wu RR et al. Am J Psychiatry 2012;169:813-821
    5. 5. Other Biomarkers• sMRI• fMRI• Cognition – E.g. cognitive impairment always predictive of poor prognosis – Improvement in cognition predicts improvement in social function
    6. 6. Sz trials• NEWMEDS – Trial design (CT + CE) – New Tools• OPTIMISE – Novel agents – Novel biomarkers (proteomics, sMRI)• IMPACT (CR + CBTp)• BeneMin
    7. 7. NEWMEDS PoC design n=40 modafinil placebo CTMCCB MCCB MCCB MCCB MCCBSB SB SB SB SB
    8. 8. mHealth• Experience Sampling Methodology• ClinTouch• World of Apps
    9. 9. Cannabidiol v AMS Leweke FM et al., Transl Psychiatry 2012:2;e94. doi:10.1038/tp.2012.15
    10. 10. FIGURE 1Eicosapentaenoic Acid Interventions in Schizophrenia: FIGURE 1 . Meta-analysis of double-blind placebo-Meta-Analysis of Randomized, Placebo-Controlled controlled EPA studies in DSM-IV schizophrenia.Studies. Random-effects model of individual and overall (last lineFusar-Poli, Paolo; Berger, Gregor of the plot) Hedges g estimate (95% confidence interval) of the effect of EPA augmentations strategies asJournal of Clinical Psychopharmacology. 32(2):179-185, compared with placebo (standard antipsychoticApril 2012. treatment) on psychotic symptoms.20,34-38DOI: 10.1097/JCP.0b013e318248b7bb © 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2
    11. 11. Oxytocin90807060 PLC OTC504030 BL 1 2 3 Feifel D et al., Biol Psych 2010 68(7) 678-80
    12. 12. Other adjunctives• Glutamatergic – [LY2140023, memantine]• Serotonergic – [MTZ, CTL, ondansetron]• Anti-inflammatory – [simvastatin, aspirin, cloecoxib]• HPA axis – [pregnenolone]• B12, folate
    13. 13. Novel psychological interventions• CR – CR + CE – CR + CBTp• Novel therapies – New applications of CBT – Adaptations of FI
    14. 14. CR + CT
    15. 15. Mean PSYRATS scores
    16. 16. RABIES
    17. 17. The MHRN environment• Hubs• CSOs’ role
    18. 18. Summary• Personalised medicine is still coming• Proteomics & Genomics: – interesting findings but methodological difficulties• Trial methodology continues to progress• Novel agents: – side effects and cognition are the current foci; – but novel APS mechanisms are an old favourite

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