NISCHR Academic Health Science Collaboration Launch www.cymru.gov.uk NISCHR Academic Health Science Collaboration Launch Millennium Stadium Cardiff 3 March 2011 1

Neuropsychiatric Disorder Research in Cardiff. www.cymru.gov.uk Neuropsychiatric Disorder Research in Cardiff. Professor Michael O’Donovan, Deputy Director of the MRC Centre for Neuropsychiatric Genetics and Genomics 2

Content At MRC Centre, we study major psychiatric disorders and some neurological disorders Schizophrenia/Bipolar (Psychosis) Depression ADHD Neurodegenerative (Alzheimer’s, Huntington’s, Parkinson’s) Multiple Sclerosis Briefly discuss why we do, what we do, and what we want to do Summarize some findings of importance (focus on Psychiatric)

Age-standardized DALYs for noncommunicable diseases by major cause group, sex and country income group, 2004

Psychiatry’s Problem Pathogenesis? Diagnosis? Treatment The development of better treatment faces two major challenges: a lack of understanding of pathophysiology a diagnostic process that is therefore largely descriptive The complexity and relative inaccessibility of the human brain together with the difficulties inherent in developing valid model systems provide major obstacles to understanding disease biology.

Mental illnesses are highly heritable 2

Molecular genetics Powerful tool for psychiatry A window on the brain

Disease Mechanisms Drug Targets NMHRI Cellular Models (BIOSI, PSYCH, MEDIC) Disease Mechanisms Drug Targets NMHRI Cellular Models Genes MRC CNGG Human and Clinical Research Disease Mechanisms Biomarkers Diagnostics Cell therapies (PSYCH, MEDIC)

Nature 2008 Nature 2009 Nature Genetics 2008 Nature 2009

Converge on (specific) synaptic pathways?

Lancet, 2010 Archives of General Psychiatry, 2010

Ion channels Nature 2007 Nature Genetics 2008 Molecular Psychiatry 2009 and 2010 Ion channels

American Journal of Human Genetics (2009) and PloS One (2010)

Neuroscience and Mental health Institute Brain imaging (CUBRIC, PETIC, EMRIC) Behavioural Neuroscience Stem cells as models and for transplantation Molecular neurobiology

iPS cell models of brain disorders Allows modelling of genetic complexity. Access to clinically and genetically characterised patient populations Expertise in stem cell work in animal models and man Chairs in stem cell as part of URI

CNVs and Health Psychosis plus Developmental delay/Mental Retardation Epilepsy Hearing impairment Cataracts Cardiac Abnormalities 16

Summary Neuropsychiatric Disorders huge burden Affected individuals (at best) pushed to the margins of society and among the most vulnerable We now have tools, expertise, and samples to unlock the biology within this generation (if not sooner) In doing so, opens up opportunities for understanding basic biology, disease modeling, developing therapeutics and better diagnostic instruments 17