This document discusses recent developments in experimental medicine for schizophrenia. It summarizes research on using pharmacogenomics and proteomics to predict prognosis, response to treatment, and identify biomarkers. It also mentions several recent clinical trials testing new agents, biomarkers, and trial designs. The document reviews studies on weight gain, metformin, EPA, cannabidiol, oxytocin, and other potential adjunctive treatments. It discusses using novel technologies like mobile health apps and progress on cognitive remediation plus cognitive-enhancing therapy or CBT.

1. Experimental medicine:
Schizophrenia Update
Richard Drake
Institute of Brain, Behaviour &
Mental Health

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. Novick D et al (2009)
Eur Neuropsychopharmacol
19 (8);542-50

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. Other Biomarkers
• sMRI
• fMRI
• Cognition
– E.g. cognitive impairment always predictive of
poor prognosis
– Improvement in cognition predicts
improvement in social function

6. Sz trials
• NEWMEDS
– Trial design (CT + CE)
– New Tools
• OPTIMISE
– Novel agents
– Novel biomarkers (proteomics, sMRI)
• IMPACT (CR + CBTp)
• BeneMin

7. NEWMEDS PoC design
n=40 modafinil
placebo
CT
MCCB MCCB MCCB MCCB MCCB
SB SB SB SB SB

8. mHealth
• Experience Sampling Methodology
• ClinTouch
• World of Apps

9. Cannabidiol v AMS
Leweke FM et al., Transl Psychiatry 2012:2;e94. doi:10.1038/tp.2012.15

10. FIGURE 1
Eicosapentaenoic 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 line
Fusar-Poli, Paolo; Berger, Gregor of the plot) Hedges' g estimate (95% confidence interval)
of the effect of EPA augmentations strategies as
Journal of Clinical Psychopharmacology. 32(2):179-185, compared with placebo (standard antipsychotic
April 2012. treatment) on psychotic symptoms.20,34-38
DOI: 10.1097/JCP.0b013e318248b7bb
© 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

11. Oxytocin
90
80
70
60 PLC
OTC
50
40
30
BL 1 2 3
Feifel D et al., Biol Psych 2010 68(7) 678-80

12. Other adjunctives
• Glutamatergic
– [LY2140023, memantine]
• Serotonergic
– [MTZ, CTL, ondansetron]
• Anti-inflammatory
– [simvastatin, aspirin, cloecoxib]
• HPA axis
– [pregnenolone]
• B12, folate

13. Novel psychological
interventions
• CR
– CR + CE
– CR + CBTp
• Novel therapies
– New applications of CBT
– Adaptations of FI

14. CR + CT

15. Mean PSYRATS scores

16. RABIES

17. The MHRN environment
• Hubs
• CSOs’ role

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
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