Interaction between genetic risk and childhood adversity in the development of psychosis and depression.

Lead Research Organisation: King's College London
Department Name: Unlisted

Abstract

Mental health problems such as depression and psychosis (e.g., schizophrenia) can be extremely disabling disorders and result in a massive cost for both the individual and NHS services. Greater understanding of what factors are involved in development and persistence of such disorders would assist attempts to prevent and treat them. One of the major factors thought to cause these disorders is an individual‘s genetic make-up but researchers have struggled to identify the exact genes involved in this process possibly because they have largely ignored the role of environmental factors. Therefore, I propose to investigate whether individuals who have a genetic risk (either positive family history or specific genetic variant) and have been exposed to potentially distressing experiences in childhood (severely beaten by or separated from their parents) are more likely to be diagnosed with depression and psychosis than individuals with only one or neither of these factors. To test this proposition I will analyse data from two different cross-sectional case-control studies: an ongoing study of psychosis patients and unaffected individuals from the same geographical area; and a completed study of depressed patients and general population controls that have provided information about their family and childhood history and given DNA samples.

Technical Summary

Aims: The research component of this fellowship aims to replicate my PhD findings of a quantitative gene-environment interaction in psychosis and extend this work to depression using molecular genetic data.

Objectives:

1. Determine whether the association with psychotic disorder is replicated for (i) severe maternal physical abuse, and (ii) maternal separation for a year or more during childhood in a different sample to that of my PhD. Furthermore, to explore whether quantitative genetic risk (parental history of mental illness) is also found to moderate these associations.

2. To explore whether there is an interaction between childhood adversity and 5-HTTLPR and BDNF val66met genotypes in recurrent unipolar depression.

Design: Study 1 forms part of the Genes and Psychosis (GAP) cross-sectional case-control study in South London whilst Study 2 utilises data from the multi-centre UK-based DeCC case-control study and the European DeNT affected sibling pairs study.

Methodology: In Study 1 400 first-presentation psychosis patients aged 18-64 years recruited from inpatient wards and a convenience sample of 400 unaffected individuals completed the Family Interview for Genetic Studies (parental history of mental illness) and the Childhood Experiences of Care and Abuse Questionnaire (childhood adversity). Logistic regression analysis will be conducted to explore the prevalence of maternal physical abuse and maternal separation amongst the psychosis cases compared to controls and the potentially confounding and moderating effects of family history of mental illness on these associations will be tested using regression, likelihood-ratio tests and synergism equations.

In Study 2, 3596 patients with recurrent unipolar depression recruited through medical clinics and a convenience sample of 573 unaffected community individuals aged 18 or over completed the Childhood Trauma Questionnaire (childhood adversity), provided a detailed family psychiatric history and blood or cheek samples which were genotyped for 5-HTTLPR and BDNF val66met polymorphisms. Chi-square tests will be used to assess prevalence of 5-HTTLPR and BDNF val66met genotypes amongst abused and non-abused depressed patients. Adversity-genotype interactions will be investigated in terms of presence of recurrent unipolar depression, age of onset of disorder and depressive symptomatology using likelihood-ratio tests and synergism equations.

Scientific & Medical opportunities: This research should improve understanding of the role adverse childhood experiences and genetic risk play in the aetiology of psychosis and depression and how these factors combine to increase risk of these disorders. These findings therefore have massive implications for prevention and treatment of both depression and psychosis.

Publications

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publication icon
Fisher H (2009) Gender differences in the association between childhood abuse and psychosis. in The British journal of psychiatry : the journal of mental science

 
Description APPA Travel Award (National Institute on Drug Abuse)
Amount £800 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 03/2011 
End 04/2011
 
Description ESRC DTC studentship
Amount £50,000 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 09/2011 
End 09/2014
 
Description ICOSR Young Investigator Award
Amount $800 (USD)
Organisation International Congress on Schizophrenia Research 
Sector Academic/University
Country Global
Start 04/2013 
End 05/2013
 
Description IEPA Young Investigator in Early Psychosis Award
Amount $1,800 (USD)
Organisation International Early Psychosis Association 
Sector Academic/University
Country Global
Start 09/2012 
End 10/2012
 
Description MRC Population Health Scientist
Amount £275,864 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2011 
End 09/2014
 
Description AESOP study 
Organisation Medical Research Council (MRC)
Country United Kingdom 
Sector Public 
PI Contribution I have been involved in training staff, collecting data, analysing data and writing up results for publication.
Collaborator Contribution Providing training, access to data and substantial intellectual input into my research.
Impact Several papers have been produced as part of this collaboration: PMID: 22353995, PMID: 22048144 , PMID: 21601792, PMID: 20855184, PMID: 20529412, PMID: 20178679, PMID: 19776204, PMID: 19336782, PMID: 19053965 and PMID: 24399191. I have given over 10 international conference presentations on this data.
Start Year 2006
 
Description ALSPAC study 
Organisation University of Bristol
Department Avon Longitudinal Study of Parents and Children (ALSPAC)
Country United Kingdom 
Sector Academic/University 
PI Contribution I analysed data from their cohort and wrote up the results for publication. I also provided statistical advice and research support during my fellowship placement at Warwick University.
Collaborator Contribution Access to the dataset and guidance over interpretation of the results of my analysis. Provided office space during a 3 month research placement at Warwick University.
Impact We have published four papers together PMID: 22941743, PMID: 23702450, PMID: 24587569 and PMID: 24342773, and have 1 more in press. I have presented this data at 4 international conferences. I also included further collaborations with this group in my successful MRC Population Health Scientist fellowship and MQ Fellowship.
Start Year 2010
 
Description ALSPAC study 
Organisation University of Warwick
Department Department of Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution I analysed data from their cohort and wrote up the results for publication. I also provided statistical advice and research support during my fellowship placement at Warwick University.
Collaborator Contribution Access to the dataset and guidance over interpretation of the results of my analysis. Provided office space during a 3 month research placement at Warwick University.
Impact We have published four papers together PMID: 22941743, PMID: 23702450, PMID: 24587569 and PMID: 24342773, and have 1 more in press. I have presented this data at 4 international conferences. I also included further collaborations with this group in my successful MRC Population Health Scientist fellowship and MQ Fellowship.
Start Year 2010
 
Description Bristol 
Organisation University of Bristol
Department School of Experimental Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution I obtained ethical approval for a study on child maltreatment, emotion processing and paranoia then conducted the assessments, analysed and wrote up the data.
Collaborator Contribution Provided me with experience in conducting experimental studies and supported me to develop and execute my own study. They also provided a computer based task for me to use and advice on analysis.
Impact I provided a lecture for the Department of Experimental Psychology. We have jointly written a journal article based on the study I conducted which is curently under review at Cognitive Neuropsychiatry.
Start Year 2010
 
Description DeCC study 
Organisation King's College London
Department Depression Case Control Study (DeCC)
Country United Kingdom 
Sector Academic/University 
PI Contribution I have analysed data and written up the results for publication. I have also provided guidance to other researchers in relation to gene x environment interaction analysis. I am also involved in testing and running analysis for an international meta-analysis that includes DeCC data.
Collaborator Contribution Provided access to the data and made an intellectual contribution to my work.
Impact We have published two papers together with myself as first author: PMID: 22840631 and PMID: 21982504 and two other papers: PMID: 23618376 and PMID: 24219410. This collaboration has also resulted in me becoming involved in an international collaborative meta-analysis and the Psychiatric Genetics Consortium.
Start Year 2009
 
Description GAP study 
Organisation King's College London
Department Institute of Psychiatry, Psychology & Neuroscience
Country United Kingdom 
Sector Academic/University 
PI Contribution I have been involved in training staff, collecting data, analysing data, supervising students and writing up results for publication.
Collaborator Contribution Access to data and allocation of a PhD student.
Impact The following papers have been published: PMID: 23764407, PMID: 23891482, PMID: 20529412, PMID: 19751968 and PMID: 25101008.
Start Year 2006
 
Description Hamburg 
Organisation University Medical Center Hamburg-Eppendorf
Country Germany 
Sector Hospitals 
PI Contribution I provided supervision to a research psychiatrist from this centre and subsequently we have analysed and written papers together.
Collaborator Contribution Provided a research psychiatrist for a 2 month placement. Since then he has written papers with me.
Impact We have published several papers together: PMID: 22048144, PMID: 22033827, PMID: 21897251, PMID: 21741038, PMID: 23168909. I was also invited to give a seminar in Hamburg for a conference they were hosting.
Start Year 2010
 
Description Lifespan 
Organisation Kingston University London
Country United Kingdom 
Sector Academic/University 
PI Contribution I provided analysis skills, interpretation of the data and writing of papers. Additionally developed ideas for them for future grant applications. I am a co-investigator on a new project grant with this group.
Collaborator Contribution Provided access to invaluable archive of lifetime adversity data originally funded by MRC and also provided extensive training on adversity and attachment measures.
Impact A joint article has been published in Child Abuse and Neglect journal: PMID: 21354622. I gave a lecture on this work at an archive seminar hosted by Lifespan. Two more journal papers are currently being jointly prepared. We jointly wrote a successful application for an ESRC project grant which started on 01/11/13.
Start Year 2009
 
Description Lifespan 
Organisation Middlesex University
Department Department of Psychology
Country United Kingdom 
Sector Academic/University 
PI Contribution I provided analysis skills, interpretation of the data and writing of papers. Additionally developed ideas for them for future grant applications. I am a co-investigator on a new project grant with this group.
Collaborator Contribution Provided access to invaluable archive of lifetime adversity data originally funded by MRC and also provided extensive training on adversity and attachment measures.
Impact A joint article has been published in Child Abuse and Neglect journal: PMID: 21354622. I gave a lecture on this work at an archive seminar hosted by Lifespan. Two more journal papers are currently being jointly prepared. We jointly wrote a successful application for an ESRC project grant which started on 01/11/13.
Start Year 2009
 
Description Lifespan 
Organisation Royal Holloway, University of London
Department Department of Health & Social Care
Country United Kingdom 
Sector Academic/University 
PI Contribution I provided analysis skills, interpretation of the data and writing of papers. Additionally developed ideas for them for future grant applications. I am a co-investigator on a new project grant with this group.
Collaborator Contribution Provided access to invaluable archive of lifetime adversity data originally funded by MRC and also provided extensive training on adversity and attachment measures.
Impact A joint article has been published in Child Abuse and Neglect journal: PMID: 21354622. I gave a lecture on this work at an archive seminar hosted by Lifespan. Two more journal papers are currently being jointly prepared. We jointly wrote a successful application for an ESRC project grant which started on 01/11/13.
Start Year 2009
 
Description MiData 
Organisation Camden and Islington NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation Central and North West London NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation Chelsea and Westminster Hospital NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation East London NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation South London and Maudsley (SLAM) NHS Foundation Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation South West London and St George's Mental Health NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation St George's University of London
Country United Kingdom 
Sector Academic/University 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description MiData 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Involved in the development of the MiData audit tool for evaluating Early Intervention in Psychosis Services across London. Provide training for clinical teams, merge anonymised data, and provide supervision for MSc students who are using the data.
Collaborator Contribution Access to clinical data across London.
Impact We have published several papers: PMID: 24025696, PMID: 23701858, PMID: 22955006, PMID: 18560782, PMID: 25214411, and PMID: 25054369. There are 2 other papers under review. I have given over 10 presentations at international conferences on this project. Eight MSc thesis have been successfully submitted on this data. I have also provided over 50 half-day training sessions for clinicians on using this tool. Additionally, using data from this study, I provided a report for the Department of Health which they are using to assist their decisions around the new Payment by Results performance indicators for psychosis services in England.
Start Year 2006
 
Description NSPCC 
Organisation National Society for the Prevention of Cruelty to Children
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution I analysed a portion of the data related to mental health outcomes of maltreatment and wrote parts of the NSPCC report. I have subsequently provided additional assistance with analysis of child maltreatment data and conducted statistical workshops for their staff.
Collaborator Contribution Provided access to large national datset of children and adolescents and gave me experience of working in a charitable organisation.
Impact We jointly wrote an extensive report on the study for the NSPCC that has been published and circulated to government officials, media and relevant stakeholders. This has also been published in part as a journal article: PMID: 23522961. We have two further papers under review. Additionally, I provided a lecture on child abuse and psychosis to an NSPCC seminar series for social workers along with statistical methods' workshops.
Start Year 2010
 
Description Rural Mental Health Australia 
Organisation Centre for Rural & Remote Mental Health (CRRMH)
Country Australia 
Sector Academic/University 
PI Contribution I spent 2 weeks at the Centre providing research consultation and discussing how my findings might be translated into practice with child and adolescent mental health clinicians. During this time I also provided training workshops and lectures.
Collaborator Contribution Provided an invaluable insight into the practical implications of my research findings and opened up possibilities for future collaborations
Impact I provided 2 training workshops on assessment of childhood abuse to adolescent mental health clinicians as well as 2 seminars on my research findings. We are also working on a joint publication using data from their centre.
Start Year 2011
 
Description Australia 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach International
Primary Audience Health professionals
Results and Impact 100 child and adolescent mental health clinicians attended 2 workshops I conducted on methods of assessing childhood abuse.

Several clinicians used their new knowledge to assess children and adolescents under their care to determine if had been abused and thus required additional treatment.
Year(s) Of Engagement Activity 2011
 
Description NSPCC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact 50 social workers attended seminar on the long-term mental health impact of child abuse. They learnt about current research in this area and discussed clinical applications.

Unknown.
Year(s) Of Engagement Activity 2010
 
Description Web article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I met with a service user journalist who developed an aticle based upon my research and it was posted on the Rethink/Institute of Psychiatry special public website targeted at carers/patients: www.mentalhealthcare.org.uk


Number of hits on article and impact unknown.
Year(s) Of Engagement Activity 2010