Social adversity, dopamine, cognition and psychosis (response to the neurobiological basis of mental health highlight)

Lead Research Organisation: King's College London
Department Name: Psychological Medicine

Abstract

Psychotic illnesses, such as schizophrenia, are common devastating conditions. Individuals with psychosis experience delusions, hallucinations and difficulties with thinking and planning. The cause of psychosis is not known. However, research shows that levels of the chemical messenger, dopamine, are increased in the brain. Other research indicates that patients have particular difficulty with planning and thinking, and this appears to be related to malfunction in the prefrontal part of the brain. Finally, the risk of developing psychosis is significantly increased in people who have been exposed to long-term social stressors. Until now, these factors have mainly been studied separately. A key aim of this project is to put information on dopamine, prefrontal brain function and social stressors in psychosis together and clarify the relationship between them. We plan to do this by measuring dopamine function and prefrontal activity using brain scanning, and measuring social stressors with specific research interviews. We will do this in people who are very vulnerable to psychosis, and have a high risk of developing the illness in the near future. We will assess these individuals at the start of the study and again after 12 months, then follow them up to find out who subsequently develops a psychotic illness. This will allow us to find which factors indicate that someone is at high risk of psychosis, and how changes in these factors over time are linked to the development of psychosis. This will help with the early identification of individuals who are vulnerable to psychosis and the development of new treatments designed to prevent the later onset of psychosis in people who are at high risk.

Technical Summary

The pathophysiological mechanisms leading to psychosis are poorly understood. Elevated striatal dopamine synthesis and release, impaired performance on tasks involving prefrontal cortex, and abnormal prefrontal activation during these tasks have been consistently reported in people with psychotic disroders, including medication na?ve patients at the onset of illness. The incidence of psychosis has been strongly associated with environmental factors such as belonging to an ethnic minority or immigrant group and living in an urban area. These factors are associated with social adversity and it has been suggested that their cumulative effect is a state of social defeat. Central dopamine activity and prefrontal cortical function are normally inter-related, and animal studies indicate that social stress and defeat can elevate both striatal and prefrontal dopamine levels. However, to date, dopaminergic function, cognitive processing and social factors in psychosis have largely been investigated separately. The aim of the present proposal is to integrate data from these different domains by studying each of them in the same individuals using PET, fMRI and social measures. These will be examined in a longitudinal study of people with an At Risk Mental State (ARMS). Around a third of this group are likely to subsequently develop psychosis, a third remain stable and a third will improve. Participants will be assessed at baseline and after 12 months. Cross-sectional comparison of the ARMS group with controls will reveal the extent to which social factors, dopaminergic activity, and prefrontal function are abnormal in people at high risk of psychosis. Further, the prospective study of this group over its divergent clinical course, with repetition of the baseline assessments, will indicate the relationship between the longitudinal trajectory of these abnormalities and clinical outcome. Our hypothesis is that these abnormalities progress in the subgroup of subjects that goes on to develop the illness, but not in these at risk subjects who do not become psychotic. This work will help to identify factors that are critical to the onset of psychosis, and may therefore inform the development of interventions designed to prevent the the onset of psychosis in people who are vulnerable to the disorder.

Publications

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publication icon
Al Fayez H (2017) Duration of untreated psychosis and pathway to care in Riyadh, Saudi Arabia. in Early intervention in psychiatry

 
Description EU-FP7
Amount € 5,998,346 (EUR)
Funding ID 603196 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 02/2013 
End 01/2018
 
Description European Commission FP7
Amount £427,000 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 01/2010 
End 12/2014
 
Description Wellcome Trust Project Grant
Amount £1,054,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2011 
End 05/2014
 
Description Link with MRC PET facility 
Organisation Medical Research Council (MRC)
Department MRC Clinical Sciences Centre (CSC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Recruitment and assessment of research participants in addition to data-analysis of 18F-DOPA PET scans
Collaborator Contribution Scanning of research participants with 18F-DOPA radiotracer to quantify presynaptic dopamine transmission in the Ultra High Risk State.
Impact Multimodal imaging - integration of fMRI and PET data Publications include those mentioned in the previous publication section
 
Description PSYSCAN 
Organisation Cambridge Cognition Ltd
Country United Kingdom 
Sector Private 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation Cantabrian Health Service
Department Clinical and Social Psychiatry Research Unit
Country Spain 
Sector Hospitals 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation Consorcio Ciber Para el Area Tematica De Salud Mental Celso Arango
Department Psychiatry
Country Spain 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation Eli Lilly & Company Ltd
Department Psychiatry
Country United States 
Sector Private 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation F. Hoffmann-La Roche AG
Country Global 
Sector Private 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation Ixico
Country United Kingdom 
Sector Private 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation Maastricht University (UM)
Department Department of Psychiatry and Neuropsychology
Country Netherlands 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation National University of Ireland
Department Department of Psychiatry
Country Ireland 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation Region Hovedstaden Psychiatry
Country Denmark 
Sector Hospitals 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation University Medical Center Utrecht (UMC)
Department Department of Psychiatry
Country Netherlands 
Sector Multiple 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation University of Cambridge
Department Department of Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation University of Edinburgh
Department Division of Psychiatry
Country United Kingdom 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation University of Göttingen
Department Department of Psychiatry and Psychotherapy
Country Germany 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description PSYSCAN 
Organisation University of Melbourne
Department Department of Psychiatry
Country Australia 
Sector Academic/University 
PI Contribution We are an integral part of this research consortium which had led to a successful bud for EU-FP7 funding
Collaborator Contribution As above
Impact The PSYSCAN project was funded by the EC as part of Framework 7. http://ec.europa.eu/research/health/medical-research/brain-research/projects/psyscan_en.html
Start Year 2013
 
Description Swedish equivalent 
Organisation Karolinska University Hospital
Country Sweden 
Sector Hospitals 
PI Contribution Data from our study has been compared with theirs
Collaborator Contribution data
Impact None yet
Start Year 2012
 
Description UK ultra high risk in psychosis network 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution In continuation of the success of the research funded by this grant we have received funding from the Wellcome trust to further this work in collaboration with the above listed institutions
Collaborator Contribution Recruiment and assessment of study participants
Impact Wellcome trust grant 'Neurobiological factors underlying the onset of psychosis'
Start Year 2011
 
Description UK ultra high risk in psychosis network 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution In continuation of the success of the research funded by this grant we have received funding from the Wellcome trust to further this work in collaboration with the above listed institutions
Collaborator Contribution Recruiment and assessment of study participants
Impact Wellcome trust grant 'Neurobiological factors underlying the onset of psychosis'
Start Year 2011
 
Description UK ultra high risk in psychosis network 
Organisation University of Warwick
Country United Kingdom 
Sector Academic/University 
PI Contribution In continuation of the success of the research funded by this grant we have received funding from the Wellcome trust to further this work in collaboration with the above listed institutions
Collaborator Contribution Recruiment and assessment of study participants
Impact Wellcome trust grant 'Neurobiological factors underlying the onset of psychosis'
Start Year 2011
 
Description 2017 BBC Horizon Program entitled 'Why did I go Mad?' 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact BBC2 Film interview: Discussed how an excess of brain chemical dopamine can lead to paranoia and delusions.
Year(s) Of Engagement Activity 2017