Award Title: Therapeutic targets for the effective psychological treatment of trauma sequelae symptoms and psychosis in patients with comorbid Schizophrenia Spectrum Disorder and Post-Traumatic Stress Disorder: Psychological and neural mechanisms.
Funder: Medical Research Council

Abstract: Aims: We will look at a specific talking therapy to help with a mental health problem that can develop following traumatic events, Post-Traumatic Stress Disorder (PTSD), in people with psychosis symptoms (which includes hearing voices and having unusual beliefs). We aim to find out how therapy works by looking at changes in the mind (trauma-related psychological processes) and in the brain (underlying neural pathways). We will also look at whether the therapy works in the same way for PTSD and psychosis symptoms.  _x000D_
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Background: PTSD symptoms following a trauma include having nightmares and flashbacks, where the event is relived in the here and now, and feeling fearful or on edge. There are four main ways in which PTSD symptoms develop: trauma memories are stored differently to everyday memories, meaning they are very intense and easily triggered; threatening beliefs about the self and others develop (e.g., “I am weak”; “people are dangerous”); being on the look-out for threat increases (called ‘hypervigilance’); and people automatically shut-off from their emotions (called ‘dissociation’), which is a way of protecting ourselves from extreme threat. Talking therapies for PTSD work by changing these four mechanisms._x000D_
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Research has shown that a history of trauma (especially abuse and neglect) increases the risk of developing psychosis symptoms, and these are often related to the trauma (e.g., hearing the voice of their past abuser). We have integrated the standard talking therapies for PTSD and for psychosis (trauma-focused cognitive-behaviour therapy for psychosis; TF-CBTp), for people who present with both. We will test if TF-CBTp works in a related study, the STAR (Study of Trauma And Recovery) trial. The current study will allow us to find out if it works by changing the above four mechanisms, and whether those changes lead to a decrease in psychosis as well as PTSD symptoms._x000D_
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Design and methods: We will recruit participants from the STAR trial over three years, which will include 300 patients across five sites in the UK. We will measure the four mechanisms in two ways: Experience Sampling Methodology (ESM), which uses a mobile phone app over a six days period to capture people’s symptoms and experiences as they unfold in their daily life; and brain scans (using a technique called functional magnetic resonance imaging, fMRI) to look at which brain processes are involved while patients carry out memory and attention psychological tasks. 200 patients will do the ESM and 80 will do the fMRI, half of whom will be receiving TF-CBTp, lasting nine months, in addition to their usual care, and the other half just their usual care. Patients will do this twice: when they start the STAR trial and nine months later. We will compare the changes in the ESM and fMRI responses over time across the two groups, and how those relate to changes in PTSD and psychosis symptoms._x000D_
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PPI, impact and dissemination: PPI in the STAR trial and this study involves consultation with experts-by-experience in the design and delivery of the study, and in making sense of the results and how to share them. We have a long history of PPI in our clinics, research, training, and sharing of our work. Understanding how the therapy works will allow us to improve future interventions to target only those mechanisms that are important. We will share our results in academic journals and clinical training, including a therapy manual, to be published by the STAR trial team.

Lay Abstract: Research Question: To enhance the effectiveness of psychological therapies for psychosis it is necessary to identify specific targets for therapeutic intervention. We will establish which psychological and neural mechanisms must be targeted to successfully treat the trauma sequelae symptoms of patients suffering from schizophrenia disorders, and whether targeting these mechanisms influences core positive symptoms of psychosis (hallucinations and delusions)._x000D_
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Background: Research has shown that traumatic experiences play a causal role in the development of schizophrenia disorders. A substantial minority of schizophrenia patients also suffer from symptoms of post-traumatic stress disorder (PTSD). Studies of PTSD patients without schizophrenia have shown that these symptoms are caused by four neural/psychological mechanisms: abnormal encoding of trauma memories; dysfunctional cognitions, hypervigilance for threat, and dissociation. Psychological treatments that target these mechanisms are effective PTSD treatments._x000D_
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Objectives: We will identify which neural and psychological mechanisms must change in dual diagnosis schizophrenia-PTSD patients for the effective treatment of their trauma sequelae symptoms. We will also determine whether influencing these mechanisms impacts on the occurrence of these patients’ psychotic symptoms._x000D_
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Methods: We will recruit our participants from the STAR (Study of Trauma And Recovery) trial, which will evaluate the effectiveness of Trauma-Focused Cognitive Behaviour Therapy for psychosis (TF-CBTp) in 300 patients at 5 sites. Half will receive TF-CBTp for 9 months and half will receive usual treatment. In this sub-study we will measure key psychological and neural processes at patients’ inception into the trial and 9-months later (coinciding with the end of therapy in the TF-CBTp group), using two methods:_x000D_
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200 patients will take part in experience sampling, a well-tested and well-tolerated method that allows psychological processes to be measured in everyday life. During testing phases soon at inception and at follow-up they will be issued with smart phones programmed to bleep 10 x a day at pseudorandom intervals over 6 days. On hearing a beep, they will be presented with a series of questions designed to measure recall of traumatic events, negative cognitions, hypervigilance and dissociation._x000D_
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80 patients will undertake an fMRI protocol, with which we will measure neural responses when encoding memories, when seeing cues related to traumatic experiences and while judging threatening faces._x000D_
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Our design will allow us to measure how these specific mechanisms change in response to TF-CBTp, the extent to which these changes predict reductions in PTSD symptoms and whether the same processes also influence psychotic symptoms in daily life._x000D_
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Timeline: The project will be completed in three years._x000D_
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Dissemination and impact: We will be able to devise ways of enhancing TF-CBTp for schizophrenia-PTSD patients; our work will therefore inform future clinical trials in terms of intervention design and outcome variables. Our findings will inform the design of future interventions for the much wider group of schizophrenia spectrum patients who, although experiencing trauma, do not meet full PTSD criteria. We will disseminate our findings in high impact psychiatric journals, at major psychiatric and clinical psychology conferences, and at special dissemination events for people with lived experience of psychosis

Research Activity Codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health Categories: MENTAL HEALTH