Environmental and Neurological Determinants of Outcome in Schizophrenia

Established: April 2006; first meeting Sept 06

Convenor (Chair): Professor Eileen Joyce, Professor of Neuropsychiatry, Institute of Neurology, University College London. (e-mail: e.joyce@ion.ucl.ac.uk)

Members: The group consists of representatives from all English MHRN hubs and the Wales Mental Health Research Network, all of whom have strong track records in publishing scientific papers and obtaining grant income. In the development of grant applications the group will encourage participation from younger clinical scientists and representation from all countries of the UK.
The initial group will be:

Cognition:
Professor Eileen Joyce, Institute of Neurology, University College London
Professor Til Wykes, Institute of Psychiatry, Kings College London

Neurobiological measures:
Professor Nicol Ferrier, University of Newcastle
Professor Peter Liddle, University of Nottingham,
Professor Phil Maguire, Institute of Psychiatry, Kings College London

Genetics:
Professor Nick Craddock, University of Cardiff
Professor Mike Owen, University of Cardiff

Epidemiology and statistics:
Professor Peter Jones, University of Cambridge
Professor Glyn Lewis, University of Bristol

Clinical, psychosocial and outcome measures:
Professor Thomas Barnes, Imperial College London
Professor Paul Bebbington, University College London
Professor Max Birchwood, University of Birmingham
Professor Shon Lewis, University of Manchester
Dr Paddy Power, South London and Maudsley Mental Health NHSTrust
Professor Swaran Singh, University of Warwick

Devolved nation members:
Genetics
Professor Nick Craddock, University of Cardiff
Professor Mike Owens, University of Cardiff

Remit and Aims:
The ultimate aim is to characterise schizophrenia to the extent that people who become psychotic for the first time can be offered individualised care plans, based on their risk factors, which include specific interventions to prevent or minimise progression of the disorder.

In the short term, our studies will highlight the importance of certain risk factors which clinicians can use, in their discussions with service users and their carers, to guide treatment and predict outcome.

Further, an understanding of risk factors for aspects of psychopathology along the mood-psychosis dimension may allow more clinically useful classifications of illness experience.

Only large studies will be powerful enough to discriminate the most significant factors which lead to the development of psychosis and determine outcome.

Candidate mechanisms which can be studied in a clinic-based multicentre setting include:
• genetic polymorphisms
• perinatal events
• cannabis use
• premorbid IQ and/or cognitive decline
• urbanicity.

Our aim is to investigate if and how these genetic and environmental variables interact to determine the clinical manifestations of schizophrenia by:
i) studying high risk and first-episode psychotic patients
ii) capitalising on work already being undertaken by the MHRN PsyGrid initiative
iii) obtaining DNA samples in the form of blood or cheek swab for genetic analysis
iv) devising brief, sensitive measures to be performed within the healthcare setting, including pre-morbid function, cognition, occupational and social function and quality of life
v) determining outcome according to psychosocial and psychopathological criteria, the latter being important because of the overlap in aetiological variables giving rise to schizophrenia and bipolar disorder
vi) including in vivo biological indices of brain function where possible, e.g. EEG, ERP, MRI
vii) compiling large databases of healthy volunteers and relatives of patients, using the same measures, for the identification of suitable endophenotypes for the genetic aspect of the research.


Current Status & Future Plans:
Although there are studies which have examined individual environmental risk factors, we wish to additionally examine the importance of the genetic background on which they occur in an epidemiological sample. Within this context, we can develop at least three research themes:
• One is the interaction between genes and adverse experiences in the causation of schizophrenia.
• A second is the examination of the complex relationship between genes, cognition and risk for schizophrenia
• A third theme would seek to understand i) the mechanisms that lead to a favourable outcome of a schizophreniform illness and ii) the specific determinants of psychopathology across the mood-psychosis spectrum.

The MHRN provides an ideal setting as only a large multi-centre epidemiological study would be able to address how the new genetics applies to schizophrenia and contributes to the heterogeneity of the disorder. It would also be able to address the contribution of environmental risk factors and inform public health policy.

6 month progress report:  the scope of the research group will be extended to include bipolar disorder given that resurgent interest in the schizophrenia-bipolar specturm in genetic studies.