Bhat, Anjali;
(2021)
Why does prenatal infection prime the brain for psychosis?
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
In this thesis, I interrogate the mechanisms of association between immune insults in prenatal development and psychotic disorders, with a particular focus on schizophrenia. Schizophrenia has been cast, from different neuroscientific perspectives, as a polygenic disorder, as a neurodevelopmental disorder and as a sensory processing disorder. The dysconnection hypothesis draws together these strands of research to construct a coherent picture of how schizophrenia may arise, specifically implicating a functional synaptopathy as the aetiological core of psychotic symptoms. One strand that has not yet been woven into this tapestry is the immune system, which has been overwhelmingly linked with psychosis in recent years. I set out to bridge these interpretations using a variety of methods, namely, statistical genetics, cell biology, electroencephalography and theoretical neurobiology. Chapter 1 is a transcriptome-wide association study of the mismatch negativity (MMN), exploring the genetic underpinnings of sensory processing itself. The MMN is an electroencephalographic signature that is consistently altered in patients with psychosis. Chapter 2 is a differential gene expression study of human neural progenitor cells stimulated in vitro with pro-inflammatory cytokines, showing suppressed transcriptional responses to inflammation in cells from people with schizophrenia. These findings are potentially important for the understanding of synaptic dysfunction in schizophrenia that may underwrite false inference of the kind associated with delusions and hallucinations. Finally, Chapter 3 considers the immune system itself as performing an elementary kind of inference: immunoceptive inference. This offers a first principles account of the immune response that extends the reach of immunology in helping to understand psychiatric disorders, as well as a new way of understanding interactions between the immune system and the brain.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Why does prenatal infection prime the brain for psychosis? |
| Event: | University College London |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2021. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10133088 |
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