STRATA - Schizophrenia: Treatment Resistance and Therapeutic Advances

Around one third of people with schizophrenia fail to respond to at least two standard antipsychotics, and thus meet NICE criteria for ‘treatment resistant schizophrenia’ (TRS). Around half of these people will eventually respond to clozapine, a drug which is uniquely effective in receiving symptoms and improving functioning in people with TRS. However, most treatment resistant patients do not receive clozapine until late in their disease, if at all. It is known that delay in clozapine treatment results in lower response rate to clozapine, so if we could know in advance who will develop TRS then they could be offered clozapine sooner and have a better outcome.

Our overarching hypothesis is that so-called ‘treatment resistant’ psychosis has a distinct neurobiology, and that biomarkers could be used to stratify people with TRS and fast-track them onto clozapine, or other future treatments that might be effective in TRS. The biomarkers identified may also help to us to understand more about how the brain is affected in TRS and how it differs from other forms of schizophrenia.

The work of the STRATA consortium was divided into four main parts.

In our ‘Phase 1’ clinical study, we studied genetic and neurochemical differences between people with treatment resistant versus treatment responsive schizophrenia. The findings of this research have been submitted for publication and will be shown here when the research is published in a peer reviewed journal.
In ‘Phase 2’, we conducted a longitudinal study to investigate dynamic changes in GLU in patients starting antipsychotics early in the illness course, since this is when prediction will be at its most useful and when critical treatment decisions need to be made to shorten the delay to effective treatment.
In the ‘STRATA-G’ project, we studied the genetics of treatment response using samples collated from collaborators around Europe.
In collaboration with H Lundbeck, we developed predictive models for TRS, using clinical and demographic data from electronic health records.

Data collection was completed in December 2019 and the results will be published over the next one to two years.

Members

Sagnik Bhattacharyya

Professor of Translational Neuroscience and Psychiatry

Charles Bowman

MRCPsych Course Administrator

Emma Butler

PhD Student

Teresa D'Oliveira Cluimaco Monteiro

Lecturer in Organisational Psychiatry & Psychology

Cathy Davies

Postdoctoral Research Associate

Kelly Diederen

Lecturer in Psychosis Studies

Alice Egerton

Reader of Neuropsychopharmacology

Kate Fielding

Executive Assistant & Research Facilitator

Paolo Fusar-Poli

Reader of Psychiatry and Youth Mental Health

Philippa Garety

Professor of Clinical Psychology

Fiona Gaughran

Reader in Psychopharmacology and Physical Health

Ryan Hammoud

PhD Student and Research Assistant

Emily Hird

Research Associate

Charlotte Horne

Postdoctoral research associate

Oliver Howes

Professor of Molecular Psychiatry

Huajie Jin

Senior Health Economist

Matthew Kempton

Senior Lecturer & BRC Precision Psychiatry Fellow

Eugenia Kravariti

Senior Lecturer in Psychosis Studies

Steven Livingstone

Senior Clinical Researcher

James Hunter MacCabe

Professor of Epidemiology and Therapeutics

Rebecca Martland

PhD Student

Philip McGuire

Professor of Psychiatry & Cognitive Neuroscience

Andrea Mechelli

Professor of Early Intervention in Mental Health

Gemma Modinos

Sir Henry Dale Fellow

Robin Murray

Professor of Psychiatric Research

Dominic Oliver

PhD Student

Rashmi Patel

MRC UKRI Health Data Research UK Clinical Fellow

Natalia Petros

PhD Student and Researcher

Susannah Pick

Post-Doctoral Research Associate

Anja Richter

Postdoctoral Research Associate

Diana Rose

Professor of User-Led Research

Mary-Jane Servito

Senior Departmental Administrator

Sukhwinder Shergill

Professor of Psychiatry & Systems Neuroscience

Sophie Smart

Research Worker

Thomas Spencer

Clinical Senior Lecturer in Early Detection & Intervention

Stefania Tognin

Lecturer in Psychosis Studies

Antonella Trotta

NIHR Maudsley BRC Research Fellow and Honorary Lecturer Senior Clinical Psychologist

Ricardo Twumasi

Lecturer in Organisational Psychiatry & Psychology

Hannah Warren

Events Co-Ordinator

Courtney Worrell

Trial Coordinator

Jenny Yiend

Reader in Cognitive Psychopathology

Jolanta Zanelli

Divisional Manager Academic Psychiatry

The causes of ethnic differences in the cause and outcome of psychosis

Why are we doing this research? 1) The NHS has made a huge investment in establishing early intervention programmes for individuals suffering their first psychotic episode. These programmes are premised on the idea that early intervention is particularly effective and that shortening the duration of untreated psychosis will improve long-term outcome. However, the evidence for this over the medium to long term is limited, and there is little information in general about what factors predict outcome. 2) There are numerous reports of high rates of psychosis in the African-Caribbean, and increasingly the Black African, populations in the UK. Furthermore, a disproportionate number of African-Caribbeans and Black Africans so diagnosed are admitted to psychiatric units compulsorily; they are also 8 times more likely to be detained in high security psychiatric hospitals. These findings have provoked much controversy and understanding how psychosis develops over time in different ethnic groups, and how sufferers interact with services, is essential for the development of effective interventions that are targeted at those most in need.

AESOP-10: THE CAUSES OF ETHNIC DIFFERENCES IN THE CAUSE AND OUTCOME OF PSYCHOSIS

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.

Contact us

Professor James MacCabe

james.maccabe@kcl.ac.uk

STRATA - Schizophrenia: Treatment Resistance and Therapeutic Advances

Members

The causes of ethnic differences in the cause and outcome of psychosis

Contact us

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