Genetics to Improve Outcomes in Schizophrenia (GENios): A within-case molecular genetic study protocol

Schizophrenia is a severe mental illness that affects how people think, feel, and behave. Whilst current treatments help with some symptoms and effects of the disorder, many people continue to struggle with poor long-term outcomes. Outcomes like repeated hospital stays, difficulties with socialising and relationships, and difficulties with finding and maintaining employment. People with lived experience of schizophrenia have identified some outcomes as research priorities. These research priorities are treatment response, hospital admissions, day-to-day living (e.g. having a job), and having relationships. Many people with schizophrenia are given antipsychotic medications to treat 'positive' symptoms (such as unusual (false or disturbing) thoughts and beliefs, and seeing and hearing things that are not there). These medications work for some people but around 25% to 30% of people with the disorder have symptoms that are not helped by standard antipsychotic treatments. These symptoms are classed as treatment-resistant. Many more people find that antipsychotic medications do not help with 'negative' symptoms (such as feeling emotionally blank and having trouble with motivation) and difficulty with cognitive abilities (such as concentrating, planning, and memory). This project, called GENios, aims to understand why outcomes differ between people with schizophrenia by looking at their genetics. We understand that social factors play an important role in outcomes but this project is specifically focused on genetics. We will analyse data from people with schizophrenia with an aim to uncover the genetic factors that influence outcomes by using data has already been collected by other research projects. We are carrying out this research in order to identify how genes and knowledge of people's genetics can help develop healthcare that is more tailored to an individual, so-called precision psychiatry. A plain English glossary of terms is included (S1 Table) to help explain technical language used in the main text.