Investigating the Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT

Psychosis is a potentially severe illness involving feelings of fear, hearing voices, and having an altered perception of reality. In the UK, psychosis contributes to 30% of the total expenditure on adult mental health and social care services and is responsible for substantial economic costs from lost productivity. The underlying neural cause of psychosis is unknown. There is growing evidence that psychologically traumatic experiences in childhood increase the risk for psychosis later in adult life, contributing to around a third of cases. These psychologically traumatic experiences include physical, sexual and emotional abuse and neglect. Since these experiences can alter brain and psychological development, they can be called developmental traumas. However, we currently do not understand precisely how childhood trauma can change how the brain works in order to cause psychosis in adults.

To date, studies have shown that developmental trauma can affect brain regions involved in specific functions, including how the brain processes emotions, like feeling threatened, and memories. These brain functions are also affected in individuals with psychosis, suggesting that developmental trauma may contribute to causing psychosis by altering these aspects of brain function. At the same time, there is an explanation for how the brain works called "Hierarchical Predictive Coding". Hierarchical predictive coding is a way of understanding how the brain can make predictions about the outside world. There is growing evidence that people with psychosis make predictions in such a way as to lead them to misinterpreting reality which may be linked to symptoms of psychosis. Importantly, hierarchical predictive coding is involved in how the brain processes threats, and also memory is essential for hierarchical predictive coding. There is also evidence that people who have experienced developmental trauma have changes in parts of the brain involved in hierarchical predictive coding. This study will therefore investigate whether changes in the way the brain processes threat, memory and hierarchical predictive coding, underlie how developmental trauma increases the risk of psychosis in adults.

This study will do this in three ways. The first component of the study will involve the use of questionnaires, computer-based psychological tasks, clinical assessments and a type of brain scan called functional magnetic resonance imaging (fMRI). This research will take place in six groups of people: healthy individuals with or without developmental trauma, individuals with subclinical psychosis symptoms with or without developmental trauma, and patients with psychosis who have or who have not experienced developmental trauma. The second part of the study will involve data that has already been collected as part of the Avon Longitudinal Study of Parents and Children (ALSPAC) study of over 10,000 people. This part of the study will involve looking at measures of brain structure and function in the ALSPAC study, which has measures of developmental trauma and brain function taken across different time points. The third part of the study will involve working in collaboration with preclinical researchers to conduct translational research initially in humans. Preclinical data has identified that trauma experienced during the vulnerable prepubertal period will disrupt circuit functioning in a way that leads to damage consistent with psychosis, as well as impairing how the individual deals with stressors as an adult.

The study has the potential to improve current understanding of the mechanisms underlying how trauma in childhood can affect the way the brain processes information and in turn cause psychosis in adults. This will assist in the development of targeted treatments, including medicines and talking therapies, to reduce the risk of psychosis following trauma exposure and improve treatments for people with psychosis who have experienced trauma.