Psychosis and schizophrenia

The main remit of the Psychosis Research Group within the Centre for Academic Mental Health (Lead: Stan Zammit) is to increase understanding of the aetiology of schizophrenia and other psychotic disorders, and improve treatment outcomes for people with such disorders.  There are a number of strands of research conducted within our group:

1)    Lifecourse epidemiology: We are interested in understanding the development of psychotic experiences, persistence of symptoms, symptom trajectories, and transition to psychotic disorder from childhood through older adulthood. We aim to apply rigorous methodology to examine the role of aetiological factors, operating prenatally through to adulthood, on development of specific symptoms of psychosis, and to understand the pathways mediating causal relationships. The aetiological factors we are examining include genetic variation, prenatal nutrient deficiency and exposure to infection, neurocognitive development, social cognition, social relationships, substance use, trauma and adversity, and the wider social environment.

2)    Biomarkers and cognitive markers for psychosis: We are studying the use of genetic, epigenetic, proteomic, neuroimaging and cognitive data to help inform prediction for incident psychotic experiences and transition to clinical disorder to inform early intervention approaches. Work on the use of such data on predicting response to treatment can also help inform a personalised or stratified medicine approach. We are particularly interested in the predictive role of cognitive processes such as reasoning biases and errors in predictive processing that can help bridge the gap between biological abnormalities observed in psychosis and experiences of psychotic phenomena.

3)    Translation from clinical samples into the general population: We are interested in studying the likely population impact of key findings from clinical samples, for example, how genetic risk for schizophrenia, as determined by cutting-edge findings from collaborative GWA studies, is manifest phenotypically during childhood in the population, and whether this changes during adolescence and adulthood. We are also studying the overlap in genetic and non-genetic factors between psychosis and other disorders, particularly autism spectrum disorders, depression and anxiety.

4)    Psychosis and trauma: We are very interested in the overlap between psychosis, post-traumatic stress disorder and borderline personality disorder, and the common role of trauma in these disorders. We are examining the role of potentially modifiable cognitive processes mediating the impact of trauma on psychotic and quasi-psychotic experiences. Ultimately, our aim is to develop interventions to reduce trauma-related symptoms in people with psychotic disorders and related psychopathology.

5)    Improving care-pathways: Effective care-pathways are key to recovery-based care, reducing unmet need and achieving parity with physical health care. We are currently quantifying and investigating the whole care-pathway (including primary and secondary-care) for people with psychosis, to identify areas for improvement and evaluate possible solutions to problems identified.

The expertise within our group includes the application of robust methodology to longitudinal data, and the application of causal analysis methodology such as use of negative controls and Mendelian Randomisation approaches. We are experienced in using epidemiological data from a number of population-based cohort studies, particularly the Avon Longitudinal study of Parents and Children (ALSPAC) and Swedish record-linkage datasets, but also work with other datasets including CPRD, NCMH, and the Pattern Study.

We are part of a Bristol Health Partners Health Integration Team (HIT) Psychosis team and have strong links with the NIHR CLAHRC West. We have strong national and international collaborations, particularly with colleagues at the Karolinska Institute in Sweden, Cardiff University, UCL, Royal College of Surgeons in Ireland, University of Warwick, and Cambridge University.

Researchers

The Researchers working in this area include Sarah Sullivan, Jonathan Evans, David Gunnell, Matt Hickman, Paul Moran, Hannah Jones, Evie Stergiakouli, Dheeraj Rai, Jon Heron, Anna Guyatt, Stan Zammit, Professor of Psychiatric Epidemiology

Selected grants

  • 2020-2024:Tracking Trajectories of Psychopathology from Infancy to Young Adulthood: an Irish national longitudinal cohort study: Cannon M (PI), Clarke M, Zammit S, Whelan R, Kelleher I, Healy C. Health Research Board Ireland (ILP-PHR-2019-009) Euros 357,142 (approx. £321,000). Summary: This study will examine the clustering and progression of psychopathology from early childhood to early adulthood
  • 2019-2023: Childhood language development and adolescent psychotic experiences. Sullivan S (PI) , Wren Y, Varley R. Mental Health Research UK Christine and Sylvia Wastall Award. £70,200. Summary: This study will investigate language development differences between children who later report psychotic experiences and those who do not.
  • 2019-2023: Mapping Neurodevelopmental Trajectories for Adult Psychiatric Disorder: ALSPAC-MRI-II. David AS (PI), Lewis G, Jones D, Zammit S, Bullmore E, Reichenberg A, Boyd A, Kempton M, De Stavola B MRC Research Grant (MR/S003436/1) £1,762,268. Summary: This study will examine changes in neuroimaging profiles over time in relation to psychotic symptomatology
  • 2018-2020: MAPPED “Improving the prediction of psychosis using primary care consultation data.” Sullivan S A (PI), Lewis G, Hamilton W, Kounali D, Nazareth I, Kessler D NIHR SPCR FR16 £135,181. Summary: This study will develop and validate a psychosis prediction model using primary care consultation data and then externally validate the model using a separate primary care database.
  • 2018–2020: Cohorts as Platforms for Mental Health research (CaP:MH). Macleod J (PI), Wright J, Bird P, Boyd A, Davis O, Haworth C, Mon-Williams M, Munafo M, Prady S, Tilling K, Timpson N, Zammit S.MRC Pathfinders Grant £1,497, 192. Summary: This study will examine prediction of psychotic experiences in cohort data linked to clinical health records
  • 2018–2021: (42 months) Investigating genetic and environmental risk for psychosis mediated through L-Type voltage gated calcium channels: Jeremy Hall (PI), Dominic Dwyer, Kerrie Thomas, Lawrence Wilkinson, Nigel Williams, Stan Zammit MRC (MR/R011397/1), £750,360. Summary: This study will examine the role of calcium channels in psychosis aetiology
  • 2018-2019: Confidence in Global Mental Health Research: M. Munafo (PI), G. Davey Smith, D. Gunnell, S, Zammit, F. Hartwig, T. Rajapaske, T. Rochat, S. Jain, B. Sebastian. MRC Global Challenges Award, £173,000. Summary: This study will fund projects researching global mental health
  • 2016-2019: An Inflammatory Biomarker Study of Psychosis: a Longitudinal Study in an At Risk Population: David Cotter (PI), Dr Mary Clarke, Professor Mary Cannon, Dr Stan Zammit, Dr Melanie Föcking, Dr Matej Oresic, Health Research Board Ireland, HRA-PHR-2015-1293, Euros 329,048 (£256,217). Summary: This study will examine biomarker profiles predicting psychosis
  • 2015-2019: Pathways to psychosis: Investigating epidemiological, cognitive and genetic mechanisms underlying development of psychotic experiences in young adults: S. Zammit (PI), M. Cannon, A. David, P. Fletcher, J. Heron, P. Holmans, P.B. Jones, G. Lewis, D. Linden, J. Macleod, M. O’Donovan, M. Owen, A. Thompson, D. Wolke. Research Grant MR/M006727/1, MRC (£1,328,163). Summary: This study will track psychotic experiences from childhood to adulthood and examine risk in relation to genetic, environmental, and cognitive exposures.

Selected publications

  • Farr, M, Pithara, C, Sullivan, S et al (2019). Pilot implementation of co-designed software for co-production in mental health care planning: A qualitative evaluation. J Ment Heal. https://doi.org/10.1080/09638237.2019.1608925

    Lloyd Evans B, Marston L, Lamb D, Mason O, Ambler G, Hunter R, Sullivan S A et al. The CORE Service Improvement Programme for mental health Crisis Resolution Teams: results from a cluster-randomised trial. (2019) Brit J of Psych (accepted for publication 3/1/19) https://doi.org/10.1186/s13063-016-1283-7

    Jones HJ, Gage SH, Heron J, Hickman M, Lewis G, Munafo MR, Zammit S. Association of Combined Patterns of Tobacco and Cannabis Use in Adolescence With Psychotic Experiences. JAMA Psychiatry. 2018;75:240-246. https://doi.org/10.1186/s13063-016-1283-7

    Jones HJ, Heron J, Hammerton G, Stochl J, Jones PB, Cannon M, Smith GD, Holmans P, Lewis G, Linden DEJ, O'Donovan MC, Owen MJ, Walters J, Zammit S, Me Research T. Investigating the genetic architecture of general and specific psychopathology in adolescence. Transl Psychiatry. 2018;8:145. https://doi.org/10.1038/s41398-018-0204-9

    Mollon J, David AS, Zammit S, Lewis G, Reichenberg A. Course of Cognitive Development From Infancy to Early Adulthood in the Psychosis Spectrum. JAMA Psychiatry. 2018;75:270-279.

    Croft J, Heron J, Teufel C, Cannon M, Wolke D, Thompson A, Houtepen L, Zammit S. Association of Trauma Type, Age of Exposure, and Frequency in Childhood and Adolescence With Psychotic Experiences in Early Adulthood. JAMA Psychiatry. 2018.

    Zammit S, Lewis C, Dawson S, Colley H, McCann H, Piekarski A, Rockliff H, Bisson J. Undetected post-traumatic stress disorder in secondary-care mental health services: systematic review. Br J Psychiatry. 2018;212:11-18.

    English JA, Lopez LM, O'Gorman A, Focking M, Hryniewiecka M, Scaife C, Sabherwal S, Wynne K, Dicker P, Rutten BPF, Lewis G, Zammit S, Cannon M, Cagney G, Cotter DR. Blood-Based Protein Changes in Childhood Are Associated With Increased Risk for Later Psychotic Disorder: Evidence From a Nested Case-Control Study of the ALSPAC Longitudinal Birth Cohort. Schizophr Bull. 2018;44:297-306.

    Ahmad A, Baxendale L, Mohr C, Sullivan S A. (2018) The association between schizotypal traits and social functioning in adolescents from the general population. J Psych Res (accepted for publication 5/11/18)

    Sullivan S A, Hamilton W, Tilling K, Redaniel T, Moran P, Lewis G. (2018) Early signs and symptoms of psychosis within primary care. JAMA Net Open (accepted for publication 20/9/2018)

    Hameed M A, Lingam R P, Zammit S, Salvi G, Lewis A, Sullivan S A (2018) Trajectories of early childhood developmental skills and early adolescent psychotic experiences: UK longitudinal cohort analysis. Front Psych 8(40) p2314

    Ijaz S, Bolea-Almanac B, Davies S, Savovic, J, Richards A, Moran P, Sullivan S A (2018) Antipsychotic polypharmacy and metabolic syndrome in schizophrenia: A review of systematic reviews. BMC Psych 18, 1, 13 p275

    Johnson S, Lamb D, Marston L, Osborn D, Mason O, Henderson C, Ambler G, Milton A, Davidson M, Christoforou M, Sullivan S et al (2018) Peer-supported self-management for people discharged from a mental health crisis team: a randomised controlled trial. Lancet) 392 10145 p409-418.

    Gage SH, Jones HJ, Burgess S, Bowden J, Davey Smith G, Zammit S, Munafo MR. Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study. Psychological medicine. 2017;47:971-980.

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