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STRATA - Schizophrenia: Treatment Resistance and Therapeutic Advances


Why are we doing this research?

People with schizophrenia suffer from a range of symptoms including hallucinations (such as hearing voices), delusions (false beliefs) and thought disorder (thoughts not flowing in a logical way), as well as 'negative symptoms' such as a lack of motivation and withdrawal from social contact. Currently, antipsychotic medication is the mainstay of treatment of schizophrenia and all existing antipsychotic medications are thought to work by acting to reduce transmission of a brain chemical called dopamine. However, even after attempts to treat the disorder with two different antipsychotics, around 30% of patients still fail to improve. When this happens, the medical guidelines recommend treatment with a different drug called clozapine. However clozapine has several side effects and requires regular blood tests, so people do not like taking it. It is also ineffective in some patients.

The result is that a large number of patients spend too long on ineffective drugs which impact greatly on their mental health, well-being and quality of life whilst the costs of ineffective treatment is a huge financial burden to the NHS, consuming 25-50% of the total national mental health budget.

This set of studies aims to build on new evidence from neuroimaging and genetics studies suggesting that those who do not respond may actually have a completely different neurochemical abnormality causing their symptoms, involving a different chemical called glutamate. There are some new medicines under development that we hope will help people whose illness has not responded to standard medicines acting on dopamine.

We aim to develop a method to predict, ultimately as early as first admission, which patients will respond to standard dopamine drugs, and which people are instead more likely to respond to the new glutamate drugs. This will allow people to receive the medicines they need straight away, without having to try ineffective drugs first.

How are we doing this research?

STRATA is broken down into several parts.

The first set of studies will use brain scans, Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) to confirm that those patients who don't respond to standard treatments have higher glutamate levels, but normal dopamine levels.

In another work package we aim to establish the extent to which genes influence clinical outcome in psychosis. Part of the reason why some people become ill may lay in genetic differences between people, in the same way that we are different in the colour of our eyes, hair etc. Our goal is to establish how individual differences in genetic risk for psychosis might influence the course of the illness and response to medication, treatment resistance, remission and full recovery in the course of the illness. This in turn will allow gaining insight into the genetic architecture underlying traits of schizophrenia.

We then hope to develop tests, using genetic markers and other information gathered, to identify in advance which people will respond to which medication types and then conduct a clinical trial to see whether prescribing medicines according to the test results gives better outcomes for patients than the 'trial and error' method by which we prescribe medicines at present. We are aiming to commence the clinical trial in 2017. We will also investigate economic benefits and, with Service User groups, investigate the acceptability of an early identification tool from the patient perspective.

Which patient group is involved?

First episode non-affective psychosis patients. These participants are asked to answer some questions and complete some assessments, give a blood and urine sample and undergo brain scans.

One of the work packages in STRATA is re-contacting previous participants from the AESOP study to collect further data (Please click here for further information).

Which sites and KCL colleagues are involved?

STRATA is a multi-centred study involving sites across the UK including The University of Manchester, Cardiff University, University of Edinburgh, University of Nottingham and Queen’s University of Belfast. The lead centre is KCL.

Prof Shitij Kapur and Dr James McCabe are leading the project, alongside Project Manager Laura Kassoumeri, Research Nurse Tracey Collier, Clinical Research Worker Dr Jacek Donocik and Research Worker Sophie Smart. The local team of collaborators/researchers comprises: Prof Philip McGuire, Prof Sir Robin Murray, Dr Oliver Howes, Dr Alice Egerton, Prof Gareth Barker, Dr David Lythgoe, Dr Diana Rose, Dr Jennifer Walke, Dr Paul McCrone, Prof Andrew Pickles and Dr James Stone.

KCL-STRATA-TeamThe STRATA team: (left to right) Laura Kassoumeri, Tracey Collier, Dr Jacek Donocik, Prof. Shitij Kapur, and Dr James MacCabe

Who funds the study?

STRATA is funded by a £5 million Medical Research Grant (MRC).

Who can I contact for further information?

Laura Kassoumeri, Project Manager at

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