Integrative model of inflammation, cognition and brain changes in individuals with psychosis


   School of Psychology

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr Maria Dauvermann, Prof Rachel Upthegrove  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Additional supervisor: Dr Zia Katshu - [Email Address Removed]

Person Specification

Applicants should have a strong background in clinical neuroscience, cognitive neuroscience or neuroimaging, and ideally a background in mental health, advanced multivariate statistical analyses or data science. They should have a commitment to research in mental health or psychiatry and hold or realistically expect to obtain at least an Upper Second-Class Honours Degree in clinical neuroscience, cognitive neuroscience, neuroimaging, psychology, mental health, data science or a related field.

Informal enquiries should be directed to the lead project supervisor Dr Maria Dauvermann - [Email Address Removed]

Project details

Abstract Psychotic disorders, including schizophrenia, affect 0.5-1% of adults with estimated annual costs of £11.8 billion in England. These conditions can result in poor functional outcome for individuals, including cognitive deficits and depressive symptoms. Cognitive deficits, alterations of structural brain measures, and mildly elevated Interleukin (IL)-6 may contribute to depressive symptoms in individuals with psychosis during early and later stages of the condition. However, we still lack a mechanistic understanding of how these interrelated factors contribute to the severity and persistence of depressive symptoms in individuals with early psychosis. This project will address previous issues by examining unique and interrelated effects between these factors. We will use structural equation modelling to study the relationships and interrelationships between cognitive deficits, IL-6 levels together with altered structural brain measures in individuals with psychotic and depressive symptoms. This newly developed model will be tested and replicated in three existing large cohort studies, including in young people with psychotic experiences. This interdisciplinary model will lead to a better understanding of the early stages of psychotic disorder and will inform more effective treatment strategies.

Aims The goal is to develop and test an integrative model to increase our understanding of complex interrelationships between factors known to contribute to depressive symptoms in early psychosis and psychotic experiences:

1.  Develop a hypothesis-driven model to examine unique and joint relationships between factors known to predict depressive symptoms in individuals with early psychosis, namely, mildly elevated levels of IL-6, lower surface area and smaller volumes of brain regions that have been putatively linked to both IL-6 levels, cognitive deficits and depressive symptoms.

2.  Test this model in a large cohort study of individuals with recent-onset psychosis (Personalised Prognostic Tools for Ealy Psychosis Management (PRONIA)).

3.  Test this model in two other large cohort studies in adolescents and young adults with psychotic experiences (Avon Longitudinal Study of Parents and Children (ALSPAC); Adolescent Brain Cognitive Development (ABCD)).

 Background Psychotic disorders can be debilitating conditions that are primarily characterised by positive and negative symptoms, as well as cognitive deficits1,2. Findings suggest that inflammatory markers, such as IL-6, may be mildly increased and causally related to the recent-onset stage of psychosis10. Additionally, mildly elevated levels of IL-6 impact cognitive problems in individuals with recent onset psychosis, and these are associated with structural brain alterations12,13. Therefore, elevated levels of IL-6 could be a key mechanism linking altered structural brain measures to cognitive function in a subpopulation of individuals with recent onset psychosis. However, it is not known how elevated levels of IL-6 affect cognitive function and brain structure in early psychosis or psychotic experiences with comorbid depressive symptoms.

 Hypotheses Using three large cohort datasets,

·     We hypothesise that mildly elevated levels of IL-6, lower surface area and smaller volumes of circumscribed brain regions would be related to depressive symptoms.

·     We assume that reduced lower surface area and smaller volumes will be associated with reduced cognitive performance and elevated IL-6 levels.

·     We predict that reduced cognitive performance will be related to elevated IL-6 levels.

Experimental Methods and Research Plan Structural equation modelling will be used to examine the relations and interrelationships between levels of IL-6, cognitive function together with related brain structural measures and depressive symptoms in early psychosis or psychotic experiences in three existing large cohort studies (recent-onset psychosis, n = 140, PRONIA; psychotic experiences, n = 9260, ABCD, and n = 257; ALSPAC). A previously developed model (Figure 1 13) will be used as the starting point to further develop and test a new model.

In this project, we will:

·     Assess IL-6 levels and putative causal associations with depressive symptoms in early psychosis and psychotic experiences.

·     Analyse structural brain Magnetic Resonance Imaging T1 scans to examine associations between altered structural brain measures (using CAT-12), depressive symptoms and cognitive deficits.

The hypothesis-driven model will be tested in the existing large cohort study PRONIA (year 1). In years 2-3, this tested model will be applied to two other existing large cohort studies of ABCD and ALSPAC to test the findings in individuals with early psychosis in adolescents and young adults with psychotic experiences. In year 4, machine learning approaches will be used to compare these findings statistically.

Expected Outcomes and Impact This project will use a model-based approach to examine mechanisms that may be underlying the aetiology of early psychosis by identifying relationships. Such findings have the potential to lead to the development of new therapeutic interventions. We anticipate that this work will lead to three publications in high-impact per-reviewed journals as well as presentations at international conferences.

Supervisor’s details

Dr Dauvermann’s research focusses on the characterisation of biopsychosocial prognostic markers of clinical and functional outcome. She uses cognitive neuroscientific and interdisciplinary methods to integrate neurobiological, psychological and psychosocial factors to better understand how youth vulnerability can influence and be influenced by neurodevelopmental and mental health conditions.

How to apply

Please click on institution link which will redirect you to the MRC AIM website which contains full information as well as the application forms to complete. Please ensure that your application is submitted by the deadline of midday (GMT) Friday 12 January 2024 as late applications will not be considered.

Biological Sciences (4) Computer Science (8) Medicine (26) Psychology (31)

Funding Notes

This is a fully funded studentship provided by the Medical Research Council.
If you are successful, you will receive a stipend (currently £18,622 per year for 2023/24) and a tuition fee waiver for 4 years.
Successful candidates will also receive an allowance for a laptop, a travel and conference allowance and an allowance for laboratory/PhD running costs.

References

1. Dauvermann MR, Donohoe G. The role of childhood trauma in cognitive performance in schizophrenia and bipolar disorder – A systematic review. Schizophr Res Cogn. 2019;16(August 2018):1-11. doi:10.1016/j.scog.2018.11.001
2. Dauvermann MR, Whalley HC, Schmidt A, et al. Computational neuropsychiatry - Schizophrenia as a cognitive brain network disorder. Front Psychiatry. 2014;5(MAR). doi:10.3389/fpsyt.2014.00030
3. Varese F, Smeets F, Drukker M, et al. Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies. Schizophr Bull. 2012;38(4):661-671. doi:10.1093/schbul/sbs050
4. Quidé Y, Tozzi L, Corcoran M, Cannon DM, Dauvermann MR. The Impact of Childhood Trauma on Developing Bipolar Disorder: Current Understanding and Ensuring Continued Progress. Neuropsychiatr Dis Treat. 2020;16:3095-3115. doi:10.2147/NDT.S285540
5. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci. 2008;9(12):947-957. doi:10.1038/nrn2513
6. Lopizzo N, Tosato S, Begni V, et al. Transcriptomic analyses and leukocyte telomere length measurement in subjects exposed to severe recent stressful life events. Transl Psychiatry. 2017;7(2):e1042. doi:10.1038/tp.2017.5
7. Treadway MT, Admon R, Arulpragasam AR, et al. Association Between Interleukin-6 and Striatal Prediction-Error Signals Following Acute Stress in Healthy Female Participants. Biol Psychiatry. 2017;82(8):570-577. doi:10.1016/j.biopsych.2017.02.1183
8. Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016;21(5):642-649. doi:10.1038/mp.2015.67
9. Corsi-Zuelli F, Loureiro CM, Shuhama R, et al. Cytokine profile in first-episode psychosis, unaffected siblings and community-based controls: the effects of familial liability and childhood maltreatment. Psychol Med. 2020;50(7):1139-1147. doi:10.1017/S0033291719001016
10. Quidé Y, Bortolasci CC, Spolding B, et al. Association between childhood trauma exposure and pro-inflammatory cytokines in schizophrenia and bipolar-I disorder. Psychol Med. 2019;49(16):2736-2744. doi:10.1017/s0033291718003690
11. Lizano P, Lutz O, Xu Y, et al. Multivariate relationships between peripheral inflammatory marker subtypes and cognitive and brain structural measures in psychosis. Mol Psychiatry. 2021;26(7):3430-3443. doi:10.1038/s41380-020-00914-0
12. Bulzacka E, Boyer L, Schürhoff F, et al. Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset. Schizophr Bull. 2016;42(5):1290-1302. doi:10.1093/schbul/sbw029
13 Corsi-Zuelli F, Donohoe G, Del-Ben CM, Griffiths LS, Lalousis PA, McKernan D, Morris D, Kelly J, McDonald C, Pariante C, Barnes NM, Khandakerf GM, Suckling S, Deakin BI, Upthegrove R, Dauvermann MR. Low mood in individuals with established schizophrenia: combining interleukin-6 levels, cognitive performance, and structural brain alterations. President's Poster Prize, British Association of Psychopharmacology, Summer Meeting 2023.

How good is research at University of Birmingham in Psychology, Psychiatry and Neuroscience?


Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

Where will I study?

Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.