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The University of Southampton

Lay Summaries of studies supported by BRAIN UK by category: Psychiatric

BRAIN UK Ref: 11/003
Pilot study – Microglia profile in schizophrenia
Dr D Boche, University of Southampton

Schizophrenia is a disorder affecting normal cognition resulting in a breakdown of coherent thought and speech processes and social and behavioural dysfunction. There appear to be a number of contributory factors including genetics and early environmental influences. Inflammation is an important component of a number of disease processes but it relevance to schizophrenia remains uncertain as evidence is contradictory. A type of cell called microglia, which are an integral part of the immune system, may exhibit different levels of activation which can be characterized by the expression of ‘marker’ molecules (the cell’s ‘phenotype’) which can be demonstrated using specific staining techniques. This study aims to use specific staining methods in order to determine the phenotypes of microglia in schizophrenia brain tissue and to determine whether such cells play a role in this particular disease.

Project Status: Closed 

Research Outputs: Grant Application x 5; Poster x 2

BRAIN UK Ref: 12/003
Neuropathological examination of neurons, glial cells, axons and molecular factors in mood and affective disorders
Prof. F Turkheimer, King’s College London

The microscopic pathological examination of brain tissue in psychiatric disorders such as schizophrenia, depression and bipolar disorders has historically been difficult to interpret. However, recent advances in specific staining techniques and corresponding image analysis have permitted a better insight into the biological and functional changes underlying these disorders. With this improvement in knowledge it may be possible to better explain clinical symptoms, identify targets for novel therapeutic intervention or to minimise side-effects to established treatments.
This study will examine affected brain tissue with reference to healthy controls using a variety of specific staining techniques to demonstrate elements of the central nervous system. Staining will be assessed using image analysis in order to quantify difference between different diagnostic groups. 

Project Status: Active

Research Outputs: Publication x 4; Presentation x 4

DatePublication title
2013 Midbrain Dopamine Function in Schizophrenia and Depression: A Post-Mortem and Positron Emission Tomographic Imaging Study
2014 Neuropathological Changes in the Substantia Nigra in Schizophrenia but Not Depression
2014 Fibrillary Astrocytes are Decreased in the Subgenual Cingulate in Schizophrenia
2015 Axonal Myelin Increase in the Callosal Genu in Depression but Not Schizophrenia
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BRAIN UK Ref: 13/011
DNA polymorphisms in mental illness (DPIM)
Dr A McQuillin, University College London

We are interested to understand whether there is a genetic basis for susceptibility to Wernicke Korsakoff’s Syndrome (WKS). This syndrome has a number of symptoms including short-term memory loss and in extreme cases psychosis. WKS is thought to be the result of a dietary deficiency of vitamin B1 which is also known as thiamine. WKS can be brought on by malnutrition but in the Western world it is often associated with chronic alcohol misuse. It is currently unclear why some people who chronically misuse alcohol develop WKS whilst others do not. If WKS is identified early enough then it is entirely treatable with intravenous administration of large doses of thiamine. The purpose of our study is to investigate genetic effects that may influence an individual’s susceptibility to the syndrome. This knowledge may have the potential to inform clinical practice in terms of identifying alcohol misusers at greatest risk of developing WKS prior to the onset of symptoms.

Project Status: Active

Research Outputs: Poster x 2

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BRAIN UK Ref: 14/005
Oligodendrocyte markers in bipolar disorder
Dr. R Carare, University of Southampton

Lysyl Oxidase (LOX) is an extracellular enzyme that is important for the formation and maintenance of the extracellular matrix (ECM). Disruption of Lox expression and/or activity results in fibrosis. Lox is expressed in the Central Nervous System (CNS) in the vasculature and is up-regulated in various neurodegenerative diseases such as Alzheimer’s Disease (AD) and Amyotrophic Lateral Sclerosis (ALS). Our data using experimental animals has identified Lox as present in the brain in the rodent. Microarray analysis identified Lox as one of the most downregulated gene affected by Lithium.
In this study we aim to label Lox and Gfap to identify if there is any change in the expression in this tissue and/or there is a morphological change in astrocytes by examining brain tissue from Bipolar disorder who have been treated with Lithium compared to aged matched control. We aim to determine whether Lithium decreases Lox expression in human brain and relate this to the changes in neurons, astrocytes and the vasculature. 

Project Status: Closed

BRAIN UK Ref: 15/010
Investigation of systemic and CNS INflammation in Schizophrenia and during acuTE psychosis: a clinical and post-mortem study (INSiTE)
Dr D Boche, University of Southampton 

1% of the population suffers from schizophrenia suffering immensely distressing symptoms. The illness emerges in early adulthood, leading to a severe impact on society both economically (£12bn a year in UK) and socially. More hospital beds are occupied by persons with schizophrenia than all other psychiatric illnesses combined. Much remains unknown about the mechanisms and causes of schizophrenia. As current treatment remains insufficient, a better understanding of the underlying neurobiology is mandatory to address its challenges adequately. An interaction of genetic and environmental risk factors during pregnancy is assumed to result in brain abnormalities, providing a background of susceptibility for new insults to result in brain malfunctioning.
Recent genetic and other studies suggest abnormalities of the immune system in schizophrenia. Therefore we propose that people with schizophrenia have a more sensitive immune system which is amplified during psychosis (when the patient has distorted contact with reality) seriously impacting the person’s life. We will study the immune system in the brains of schizophrenia patients who died with or without psychosis compared to control brains.
This project will generate highly novel information about the contribution of systemic and brain inflammation in schizophrenia and support future diagnostic and therapeutic developments. 

Project Status: Active

Research Outputs: Publication; Grant Application; Poster

DatePublication title
2017 Microglia and Brain Plasticity in Acute Psychosis and Schizophrenia Illness Course: A Meta-Review
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BRAIN UK Ref: 15/021
Investigation of astrogliosis and Lox expression in the Occipital Lobe of Bipolar Disease affected patients.
Dr R Carare, University of Southampton 

Using tissue from Brain UK we have already demonstrated that a novel enzyme named LOX is under expressed in the supporting cells in bipolar disorder. We now wish to expand upon these findings by increasing the sample size to increase statistical significance and by using sophisticated technology that could determine the origin of LOX and why it is affected in bipolar disorder.

Project Status: Active

Research Outputs: Presentation

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