B4241 - Oestrogen as a protective factor for psychosis - 06/02/2023

B number: 
B4241
Principal applicant name: 
Sarah Sullivan | University of Bristol (England)
Co-applicants: 
Prof Carol Joinson, Prof Abigail Fraser, Prof Martha Hickey, Prof Stan Zammit, Prof Golam Khandaker, Dr Helen Bould
Title of project: 
Oestrogen as a protective factor for psychosis
Proposal summary: 

Psychosis is a severe mental illness. An example is schizophrenia. Symptoms of psychosis can include hearing voices and having strange and fixed ideas. It is not rare. Each person has a three in one hundred chance of developing psychosis over their lifetime. Psychosis has a very destructive effect on people's lives because the first episode often happens during late teens or early adulthood, at a time when people are finishing education or starting careers and forming long-term meaningful relationships. Psychosis can interrupt these important processes making it difficult for sufferers to catch up with the progress of their peers. It is also extremely expensive for the NHS to treat because it often requires lifetime medication and periods in psychiatric hospital. A recent study in England reported annual costs of £2 billion. Unfortunately, the outcomes for people with psychosis are often poor. About 25% of people relapse within 3 years of recovery, are likely to be unemployed long-term and have a poor quality of life. Relapses are very distressing for the patient and their family and increase treatment costs for the NHS.

Men have a higher risk of psychosis than women when young, but women are more at risk in later middle age. It has been suggested that this might be because a female sex hormone called oestrogen, protects women from psychosis from when they start their periods (when oestrogen levels rise) until the menopause (when oestrogen levels drop). Currently, there is not enough good quality evidence to know if this is correct. It is very important to find out whether this is true because an understanding of the underlying causes of a new episode of psychosis will help us to predict who is most risk and get them the help they need as soon as possible. This will, in turn, improve outcomes by reducing the
chance of a relapse and therefore reduce treatment costs for the NHS. I will use data from population-based long-term studies to see whether the age at which women start their periods, or experience menopause, is associated with risk of psychosis. If the oestrogen theory is correct, a later age of starting periods and an earlier age of experiencing the menopause will be linked to increased risk of psychosis. I will also use NHS prescription data to see if taking hormonal contraceptives and hormone replacement therapy, affect psychosis risk. Both these medications contain either oestrogen, or progesterone (another important female sex hormone) or both. Therefore, if the oestrogen theory is correct,
they may reduce the risk of psychosis. We will also be able to find out if progesterone has a role in risk of psychosis. This study proposes a new way to investigate this question using population-based data linked to NHS data.

Population data and NHS data are useful to researchers because they contain very large numbers of participants but there are also problems such as missing data and inaccurate recording, which can make the findings difficult to understand. To strengthen our findings in population data, we will also use genetic data which contains information about individual risk of psychosis and a woman's reproductive stage in life. These data have smaller numbers of participants than the population data and NHS data, but they do not have the same problems with missing data or inaccurate recording. Therefore, if we can find the same result in both types of data, we can be more confident that lower levels of oestrogen increase psychosis risk. We will also use population data from Sweden to find out whether the findings are the same outside the UK. The findings from this work will help doctors to identify women at greater risk of psychosis much earlier than happens now and provide opportunities for offering treatments that might prevent psychosis developing, like psychological or hormone-based drug therapies.

Impact of research: 
If oestrogen is protective for risk of psychosis, oestrogen levels could be one of the multiple factors that predict risk in older women.
Date proposal received: 
Tuesday, 24 January, 2023
Date proposal approved: 
Wednesday, 25 January, 2023
Keywords: 
Mental health - Psychology, Psychiatry, Cognition, Mental health, GWAS, Linkage, Liver function, Mendelian randomisation, Mothers - maternal age, menopause, obstetrics