Title: Visual Impairment in Psychosis: Cause, Consequence, or Biomarker?
Funder: Department of Health and Social Care

Abstract: Research Question: Is visual impairment a cause, consequence, or biomarker of psychotic illness? Background: Approximately 1.3 billion people worldwide have visual impairment, and over 23 million have psychotic illnesses. Previous research indicates these conditions are associated. Visual impairment may be a cause, consequence, or biomarker of psychotic illnesses. Greater understanding of the relative importance of these pathways could allow implementation of more evidence-based approaches to the mental health care of people with visual impairment, and inform research into prevention and treatment of psychosis. I will explore each pathway in four large datasets. Aims and Objectives:1. To synthesise current knowledge regarding associations between psychotic illnesses and visual impairment. 2. To use data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test two hypotheses: Single Nucleotide Polymorphisms (SNPs) associated with reduced visual acuity in the UK Biobank are associated with a diagnosis of psychotic illness in the PGC. SNPs associated with a diagnosis of schizophrenia in the PGC are associated with reduced visual acuity in UK Biobank.3. To use Avon Longitudinal Study of Parents and Children (ALSPAC) data to test hypotheses that: Childhood visual impairment is associated with future psychotic symptoms. Varying degrees of visual impairment are differentially associated with this outcome.4. To use data from the Israeli Draft Board Registry to test hypotheses that: Visual impairment by age 18 is associated with future hospitalisation for psychotic illness. Varying degrees of visual impairment are differentially associated with this outcome.5. To assess social isolation, loneliness, smoking, hypertension and diabetes as potential mediators of associations between visual impairment and psychotic illness. 6. To find out if associations differ between older and younger people. Methods:I will conduct systematic reviews searching for studies reporting (a) the risk of psychotic illness in people with visual impairment relative to those without; and (b) or a risk of visual impairment in people with psychotic illnesses relative to those without. I will use two-sample Mendelian Randomisation in UK Biobank and Psychiatric Genomics Consortium to test hypotheses 2a and 2b. Mendelian randomisation exploits the naturally-occurring random assignment of genetic variants at conception to test causal hypotheses whilst minimising confounding and ensuring temporality. I will use longitudinal ALSPAC and Israeli Draft Board Registry data to test the hypotheses 3a, 3b, 4a, and 4b. Mediators will be explored for any relevant associations. Timeline for Delivery: 0-6 months: Systematic review; database management 6-18 months: Analyse data from UK Biobank, PGC and ALSPAC 12-28 months: Analysis of Israeli Draft Board Registry data 28-36 months: Write up thesis and submit Anticipated impact and dissemination:I will publish findings in peer-reviewed journals. I will chair a 6-monthly implementation group, with patient and public, clinical and academic membership. The group will focus on pathways to impact and advise on opportunities to disseminate findings via healthcare professionals, charities, and patient and carer groups, and develop plans to influence clinical practice, for example by responding to NICE and other relevant consultations. I will develop plans for an advanced fellowship.

Lay abstract: Eyesight Problems and Psychotic Illnesses: What's the Link? Psychotic illnesses affect about 1% of people. Symptoms include hearing voices and having confusing and distressing thoughts. These can have a large effect on people's lives. People with psychotic illnesses seem to have more eyesight problems. We don't know why. Here are three possible reasons: 1: They find it hard to look after their eyes. For example, it might be harder to get to the optician's. 2: They have brain changes that cause both eyesight problems and psychotic illnesses. 3: Eyesight problems increase someone's chances of having a psychotic illness. I plan to look at which of these reasons best explains why eyesight problems and psychotic illnesses occur together more than would happen by chance. If people with psychotic illnesses have less good eye care, we need to improve this. If the same brain changes are causing poor eyesight and psychotic illnesses, this would teach us more about the causes of psychotic illnesses. If eyesight problems lead to psychotic illnesses, then improving eye health could help to prevent or treat psychotic illnesses. I will start by reviewing past research, so that I base my work on the most up-to-date information. I will then carry out research using four big datasets: UK Biobank has information about the health and circumstances, eyesight and genetics of over half a million people aged 40 to 69. The Psychiatric Genomics Consortium (PGC) has genetic information on over 34,000 people with psychotic illnesses and 45,000 people without. The Avon Longitudinal Study of Parents and Children (ALSPAC) has data on 14,500 UK families. The children are 24 and have been followed up since before birth. The Israeli Draft Board Registry: This holds data collected from over 600,000 Israeli 17-year-olds from when they have health and eye checks to decide if they can join the armed forces.Genes are present before birth, so are decided before any psychotic illness develops. I will see if people with genes for short-sight have more psychotic illnesses. If they do, this suggests that poor eyesight increases a person's chances of getting psychotic illnesses. I will also find out if genes for psychotic illnesses are linked with eyesight problems. This would suggest the reverse: that people with psychotic illnesses have a higher chance of developing poor eyesight. I will also find out if teenagers or children with eyesight problems are more likely to have a psychotic illness later on. If so, I will see whether people with worse eyesight problems have a higher chance of getting psychosis than people with milder eyesight problems. This will allow me to test the theory that moderate eyesight problems carry the highest risk, because they are harder for the brain to adjust to. I will chair an advisory group every 6 months. People with psychotic illnesses and people with eyesight problems will be members and will help to decide how the research is run. The group will also include carers, charity members and doctors. We will discuss how to use any results to improve healthcare for people with eyesight problems and psychotic illnesses. When the research is finished, I will tell healthcare professionals and researchers about my results at meetings and in journals. I will write about them in publications aimed at people with mental health and eyesight problems. I will also present findings to public groups, through links with the Royal National Institute for the Blind (RNIB) and a forum of mental health service users. People with eyesight problems and mental health service users helped to write this summary.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MENTAL HEALTH;EYE