Dysfunction of Respiratory Enzymes in Adults with Mental Illness
Research type
Research Study
Full title
The role of mitochondrial complex 1 (MC1) in brain and cardiac dysfunction in serious mental illness.
IRAS ID
274226
Contact name
Oliver Howes
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
4 years, 0 months, 0 days
Research summary
Mental health problems enduring for a long time and causing a high degree of disability are termed Serious Mental Illness (SMI). This category includes illnesses such as schizophrenia, bipolar affective disorder and major depressive disorder. While these conditions differ from each other in many ways, cognitive symptoms - including problems with memory – and increased rates of heart disease are found in all of them to varying degrees.\n\nStudies looking at brain structure and function in SMI show reductions in the size of the front part of the brain, and reduced glucose uptake, a measure of energy production. Reductions in these measures mean lower scores in memory tests. Post-mortem and genetic studies suggest that abnormalities in energy-producing parts of brain cells (termed “mitochondria”) might contribute to neural and cardiac dysfunction in SMI.\n\nA recent study showed that a medication called methylene blue (MB) increased brain activity, as well as overall performance in memory tests, in healthy volunteers. MB works by increasing energy production in mitochondria by bypassing a particular enzyme (called Mitochondrial Complex One, MC1), which in turn increases the activity of brain cells. If MC1 dysfunction contributed significantly to cardiac and neural function in SMI, we would expect greater MB-induced increases in cardiac and neural function in SMI compared to healthy controls. Understanding this could help us develop new treatments, targeting mitochondrial function.\n\nWe will use magnetic resonance imaging (MRI – a scan using strong magnets) to measure brain activity and cardiac function in people with SMI and healthy controls. We will scan volunteers twice, once after MB and once after placebo. \n\nParticipants would visit us three times, for around two hours each time, at the Robert Steiner MRI Unit, Hammersmith Hospital over three years. We will recruit people with SMI from NHS clinics.\n\n\n
REC name
North of Scotland Research Ethics Committee 1
REC reference
20/NS/0056
Date of REC Opinion
4 May 2020
REC opinion
Favourable Opinion