Medical Research Scotland is one of the largest and most comprehensive independent research charities in Scotland. Unlike most medical research charities, our funding isn't restricted to any one disease or condition, we support high-quality research that aims to improve the understanding, diagnosis, treatment and prevention of all diseases and disease mechanisms.
Awards in the past 20 years
The following are some of the awards we made for research into psychiatric disease.
Dr Alasdair MacKenzie (School of Medical Sciences, Aberdeen University) to supervise Ms Elizabeth Hay during her PhD Studentship, "The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy." This research will also involve close working with GW Pharmaceuticals.
The cannabinoid-1 receptor protein (CB1) has been implicated in obesity, addiction and chronic inflammatory disease and represents an excellent drug target for their treatment. However, promising drugs designed against CB1 can cause unacceptable side-effects in a proportion of patients. Little evidence exists that mutations in the gene that makes CB1 are involved in disease progression or drug side effects. Could mis-regulation of the CB1 gene be to blame? We have shown that obesity and addiction associated mutations alter genetic control switches required to regulate the healthy expression of the CB1 gene. We also show that activating the CB1 protein activates these switches, demonstrating self-regulation, but that disease-associated mutations disable these control switches. These mutations also change susceptibility of the switches to epigenetic modification; a process influenced by early life events. We will further investigate the switches that regulate the CB1 gene in brain regions that control inflammation and appetite where we believe genetics and the environment interact to influence disease susceptibility and drug-side effects. This project will also test novel drug treatments in development by GW Pharmaceuticals to manipulate these switches aiming to accelerate the development of personalised cures for inflammatory diseases, addiction and obesity.
Dr Berndt Mueller (School of Medical Sciences, Aberdeen University) to supervise Miss Jihan Anderson during her PhD Studentship "Identification and correction of the molecular and cellular defects in neurons caused by deregulation of the novel autism susceptibility gene EIF4E - an opportunity to develop treatments for autism". This research will also involve close working with Dundee Cell Products.
Autism is an as yet untreatable but common lifelong childhood-onset neurodevelopmental disorder affecting 1 in 200 individuals. The underlying genetics is complex and poorly understood. We have identified EIF4E as an autism susceptibility gene. In addition, mutations in several genes known to control the activity of eIF4E protein cause autism or syndromes with autistic features. Together, this strongly supports our hypothesis that over-expression of eIF4E protein predisposes to autism and we propose that correction of eIF4E over-expression could form the basis of effective treatment of autism. To test this we will identify the abnormalities caused by eIF4E over-expression in neurones using two complementary approaches: we will determine the effect of eIF4E over-expression on the differentiation and behaviour of neurones using live-cell microscopy and immunocytochemistry, and we will identify changes in protein components caused by eIF4E over-expression using state-of-the-art protein profiling methods. Together, this will increase our understanding of the underlying molecular events leading to the development of autism. We will produce reagents for the detection of proteins whose levels are changed, as they may serve as marker proteins for autism. Finally, we will test whether any changes occurring in neurones when eIF4E is over-expressed can be reversed by compounds known to control eIF4E activity. This work will produce reagents to identify subjects with autism caused by dysregulation of eIF4E and will lead to screens that are expected to identify novel compounds to treat this condition.
Dr Andrew Sutherland (School of Chemistry, Glasgow University) to supervise Nikki Sloan during her PhD Studentship "New Metal Catalysed Methods for the Efficient, Non-toxic Generation of PET and SPECT Tracers: Molecular Imaging of Neurological Disease". This research will also involve close working with GE Healthcare.
Radionuclide molecular imaging is increasingly used for the early diagnosis of both neurological diseases and cancer. However, the widespread application of this technology is being limited due to current methods of generating the imaging agents which can involve unstable, highly toxic precursors. In collaboration with GE Healthcare, this project will investigate new transiton metal-catalysed chemical processes that will allow simple, easy access to PET and SPECT tracers from readily available, non-toxic starting materials. In particular, the project will investigate the use of nickel catalysts for the incorporation of radiohalogens into aromatic compounds, structural motifs that are found extensively in molecular tracers. On development of each new reaction, the versatility of this process will be demonstrated by the preparation of molecular tracers used in the imaging of cancer and neurological disorders, particularly Alzheimer's disease. Discovery and successful development of these new chemical transformations for the non-toxic and facile preparation of PET and SPECT imaging agents will accelerate the application of this technology across the NHS and the pharmaceutical/life sciences industries.
£149,861 to Dr Bing Lang, Dr Sanbing Shen & Professor Colin D. McCaig (Institute of Medical Sciences, Aberdeen University) and Dr Colin Smith (Pathology, Western General Hospital, Edinburgh), for a three-year project aiming to uncover novel biomarkers for schizophrenia.
Schizophrenia and bipolar disorder affect 1 in 50 people. No effective medication is available and current antipsychotic drugs often have unpleasant side-effects. This project aims to explain aspects of abnormal brain development in schizophrenia and identify new biomarkers which may be useful in future drug development.
£97,672 over 30 months to Dr Andrew C. Stanfield and colleagues Professors Eve Johnstone and Stephen M. Lawrie (all of the Department of Psychiatry, University of Edinburgh) and Professor Peter M. McKenna (Department of Psychological Medicine, University of Glasgow), for a clinical, neuropsychological and MRI study comparing autism spectrum disorders and schizophrenia spectrum disorders.
The diagnosis of most psychiatric diseases is based on the patient's signs and symptoms, many of which are not specific to a particular disorder, so cannot be made with certainty. This can have important consequences for patient management. This project aims to find markers which will help to distinguish between the similar clinical signs and symptoms of schizophrenia and autism, with a view to improving diagnosis in these conditions.
The second Medical Research Scotland/Mrs Mary Tyson Fellowship was awarded to Dr Anna Sutherland (Department of Psychological Medicine, University of Glasgow) for her project entitled: "Perceived interpersonal threat as a unifying psychological model in Cluster B personality disorder".
Personality disorders are particularly difficult to treat and have significant social and economic costs. The aim of this project is to develop an effective, evidence-based cognitive model to improve clinical intervention aimed at reducing the antisocial and self-harming behaviours characteristic of these personality disorders.
The Medical Research Scotland/Mrs Jean V. Baxter Medical Research Fellowship 2006-08 was awarded to Dr Marie-Astrid Pezze (Centre for Cognitive & Neural Systems, University of Edinburgh) for her project entitled "Dopamine signalling from the ventral tegmental area to the hippocampus, novelty, and memory encoding: investigating the substrates of cognitive deficits in schizophrenia".
This work will identify possible links between the effects of current treatments for, and the memory impairment associated with, schizophrenia.
£58,637 over one year to Dr Jonathan T.O. Cavanagh (Psychological Medicine, Glasgow University), Professor David Wyper & Dr Jim Patterson (Clinical Physics, Southern General Hospital, Glasgow) for a SPECT study of the ratio of dopamine transporter to serotonin transporter in treatment-resistant compared with treatment-responsive depression.
In up to 30% of cases, depression is resistant to conventional treatment. This research will study the ratios of uptake of the neurotransmitters dopamine and serotonin in the brains of treatment-responsive and resistant depression to understand how the brain responds.
£99,278 over three years to Dr Joanne K. Miller & Professor David Porteous (Medical Genetics, Edinburgh University) to carry out a functional analysis of a candidate schizophrenia gene, disrupted by a chromosomal translocation in patients with schizophrenia.
DISC1 is one of the few genes known to increase a person's susceptibility of developing schizophrenia. However, its normal function is unknown so this research will investigate this and consider the normal signalling pathways it is involved in.
£69,664 over two years to Drs Benjamin S. Pickard & Walter J. Muir and Professor Douglas H.R. Blackwood (Psychiatry) and Professor David Porteous (Molecular Medicine Centre, Edinburgh University) for a study combining fluorescence in situ hybridisation with molecular bio-informatics to isolate genes for psychiatric illness.
Using modern biological techniques and molecular bioinformatics this research will study the genes associated with psychiatric illnesses such as schizophrenia.
£43,000 over 14 months to Drs Gerome D. Breen & David St Clair (Mental Health, Aberdeen University) to investigate the role of single nucleotide polymorphisms in the pharmacogenetics and genetics of mood disorders.
Even small changes in genetic sequences can have an impact upon health and the body's response to drugs. This research will look at such a small change and its role in mood disorders.
£30,391 to Dr Kieran Breen (Pharmacology, Ninewells Hospital & Medical School, Dundee) for a one-year study of the role of Tau protein glycosylation in the generation of neurofibrillary tangles associated with Alzheimer's Disease.
£101,434 to Dr Neil P. Prentice (Brain Metabolism Unit) and Professor Eve C. Johnstone (Psychiatry, Royal Edinburgh Hosptial) for a three-year study of the early and late onset of depressive illness in the elderly.