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Research

Research in the Department of Psychosis Studies

Research-psychosis-webThe Department of Psychosis Studies is the largest department within the Institute of Psychiatry, Psychology and Neuroscience and is one of the world’s largest groups conducting research on psychosis. Its staff have produced over 1300 scientific publications in the last 5 years and hold approximately £25 million in research grant income. The Institute has received the highest possible ranking (5*) in recent UK Research Assessment Exercises.

Our research is focused on understanding the mechanisms underlying psychotic experiences and psychotic disorders, and on using this knowledge to inform the development of new clinical assessments and treatments. This work involves a wide range of methodologies, including neuroimaging, genomics, psychopathology, cognition, epidemiology, and the assessment of peripheral markers. A key feature of the research is the integration of biological and psychosocial factors.

The department is directly integrated with high quality clinical services for psychosis in the Psychosis Clinical Academic Group (CAG), part of the South London And Maudsley NHS Trust. This specialised clinical infrastructure facilitates the involvement of patients in research, and the rapid translation of research findings into clinical practice.

Epidemiology and Risk Factor research

We have a strong track record of population-based research, identifying the causes, course and impact of psychosis across the lifespan.  Much of our work is conducted in collaboration with international partners in Sweden, Denmark and the Netherlands.  The risk factors that we are currently studying include ethnicity, low birth weight,  childhood cognitive functioning, cannabis use, cigarette smoking and creativity.  We also study the impact of psychosis on other outcomes such as number of offspring, risk of suicide, employment and long-term outcome.  We employ epidemiology and population-based research to most of the other research areas listed below, particularly cognition, cannabis, neurodevelopment and treatment resistance.  

People at ultra high risk for psychosis

The department is a leading centre for research on people at ultra high risk (UHR) for psychosis. Research in this phase provide a powerful means of investigating the factors that lead to the onset of psychosis, as a given individual can be studied prospectively, before, during and after illness onset, with minimal confounding effects of previous illness or treatment. Our recent work has shown that many of the neurobiological, cognitive and behavioural features of psychosis predate the onset of the disorder, and that these alterations predict subsequent clinical and functional outcomes. Current work in this area is focused on translating these findings into clinical tools that can be used to predict whether a given individual with recover or go on to develop a disorder, so that intervention can be tailored to their personal needs. This research involves international multi-centre consortia (EU-GEI, PSYSCAN, MET-PSY), which are recruiting samples that will be large enough to yield definitive findings. Research in this area is facilitated by direct integration with OASIS, one the world’s largest clinical services for UHR subjects, and part of the Early Intervention Care Pathway of the Psychosis CAG.

First episode psychosis

The department has an international reputation for research in first episode psychosis. Our work provided some of the first evidence that ethnicity, childhood adversity and cannabis use are major risk factors for psychosis, and has shown that neuroimaging abnormalities at this stage can be used to predict the course of illness following the first episode. Current work is examining how genetic and environmental factors interact to influence the risk of psychosis, as part of the EU-GEI study, and is investigating the neurobiological factors that determine the response to the first antipsychotic treatment, as part of the OPTIMISE programme. Follow up of cohorts originally recruited several years ago is revealing the factors at presentation that best predict long-term clinical, functional and health economic outcomes. Research in this area is facilitated by direct links with local early intervention clinical teams (LEO, STEP, COAST & LEI), which are part of the Early Intervention Care Pathway of the Psychosis CAG.

Neurodevelopment

Psychotic disorders may result from perturbations at an early stage in development. Studies in people who are born very preterm provide a powerful way of examining the effects of this on cognitive function and mental health in later life. Our department has conducted a series of prospective studies using neuroimaging, neuropsychology and clinical assessments in a large cohort of people who were born preterm and are now entering adulthood.

Chiara Nosarti

Treatment Resistance

Research in this area is focused on understanding the neurobiological mechanisms that determine how patients with psychosis respond to treatment. At present there is a long delay before patients who respond poorly to conventional treatment are identified and are offered appropriate alternative treatment. We are developing ways to use neuroimaging, genetic and peripheral biomarkers to identify this subgroup of patients as early as possible. At present the treatment with the strongest evidence base in such patients is the antipsychotic drug, clozapine. We are the lead centre in an EU-funded international consortium, CRESTAR, which aims to understand more about how clozapine works, to predict which patients are most likely to respond, and who is likely to suffer adverse effects. The department is currently leading a national network for research on stratified medicine in treatment resistant schizophrenia (STRATA) funded by the MRC. At present all licensed pharmacological treatments for psychosis act on D2 receptors. Much of our research is designed to identify alternative therapeutic targets and evaluate compounds that act on these. For example, neuroimaging measures of central dopamine and glutamate function may be used to identify patients who are unlikely to respond to treatment with conventional antipsychotic medication. We are currently assessing the effectiveness of novel treatments that influence the glutamate system, the endocannabinoid system, and PDE10 inhibitors. These studies typically involve the use of neuroimaging and other assessments to investigate the mechanisms of action of these compounds, with patients studied before and after the introduction of treatment.

Cannabis and endocannabinoids

The department has pioneered research on the effects of cannabis use on psychotic symptoms and on the risk of developing a psychotic disorder, and on the role of the endocannabinoid system in psychosis. This work has helped to highlight the effects of cannabis use on mental health and has influenced UK health policy in this area. Current research is investigating the impact of cannabis use on relapse in patients with psychotic disorders, and the extent to which its effects depend on specific genetic factors. Research using functional and neurochemical imaging is examining how cannabinoids act on the brain to modulate cognitive and emotional processing, and the role of CB1 receptors in psychosis. We are also evaluating the therapeutic potential of endocannabinoids, such as CBD, in a series of experimental medicine studies and clinical trials. 

Psychopharmacology and novel treatments

Research work in this area is focused on understanding how changes in neurotransmitter function impact on psychosis, and using this knowledge to develop and evaluate novel treatments. Neuroimaging studies using MR spectroscopy, PET and pharmacological fMRI have revealed the role of the glutamate, GABA, dopamine and endocannabinoid systems in psychosis. These approaches are combined with clinical trials of novel compounds, permitting analysis of their mechanism of action as well as their clinical efficacy. Many of these studies are supported by the NIHR Biomedical Research Centre (BRC) at the Maudsley Hospital, and the Clinical Research Facility at King’s College Hospital. Ongoing work is assessing the effects of CBD, glycine reuptake inhibitors, minocycline, oxytocin and vitamin D in patients with psychosis and people at UHR for psychosis.

Cognition in psychosis

The department has had a longstanding research interest in the cognitive dysfunction associated with psychotic illness. Experimental work has ranged from exploration of the cognitive mechanisms underlying the experience of positive psychotic symptoms such as auditory hallucinations and delusions, through to observational work identifying the core cognitive performance deficits associated with different forms of psychotic illness. More recently, there has been an increasing focus on testing treatments for the common cognitive dysfunction associated with psychosis – across a range of modalities including psychological, pharmacological and the combination of both – using a variety of different approaches and techniques. These lie on a spectrum from novel experimental medicine studies through to phase 3 commercial clinical studies; and include the use of a broad range of multi-modal techniques including population based epidemiological studies, genetic and neuroimaging investigations of selected sub-samples of psychosis sufferers – based on symptom type or stage of illness. This work links synergistically with initiatives within local and national clinical services to offer a more comprehensive standardized assessment of cognitive symptoms, with a view to early introduction of emerging early research-based therapies.

Positron Emission Tomography

The department has enjoyed a long standing working relationship with the PET centre at Hammersmith hospital, and more recently KCL has joined with UCL and Imperial College to support the world class IMANVOA PET facility at this site. The department also uses the PET facility at St Thomas’ hospital. PET provides the opportunity to study neurotransmitter systems and pathological processes at a molecular level of specificity, and our staff have used this approach to establish the role of presynaptic dopamine function in the early phase of psychosis, and in relation to treatment response and resistance. Current work includes studies of the endocannabinoid system, the glutamate system, GABA, and neuroinflammation.

Oliver Howes

Peripheral markers

A key goal for research in psychosis is use scientific findings to improve clinical practice. At present, the assessment and management of patients with psychosis does not involve any objective biological measures. However, there is increasing evidence that the assessment of markers of inflammatory processes, antibodies to CNS antigens, and proteomic and metabolomic factors provide a way of investigating the pathophysiology of psychosis and stratifying patient groups. As these assessments can usually be made using samples of peripheral blood, they are ideally suited for the development of tests that could be implemented in a clinical setting.

Physical health in psychosis

There is increasing recognition of the reduced life expectancy and poor physical health of patients with psychosis, with a Department of Health White Paper on this topic in 2011. Our department has recently completed IMPACT, one of the first major studies in this area which has highlighted the prevalence and severity of metabolic abnormalities in psychosis. Current work involves the evaluation of a range of novel approaches designed to improve the assessment and treatment of physical health in psychosis, including trials of e-cigarettes, exercise programmes, and novel pharmacological treatments, such as Vitamin D. Many of these initiatives are focused on the Early Intervention Care Pathway in the Psychosis CAG, so that the impact on physical health begins as early as possible.

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