Aims of proposal: The aims of this proposal fall within 3 work themes:

Work theme 1: Epidemiology and environmental risk. We aim to investigate the development of psychotic experiences, at-risk mental states and transition to psychotic disorder from childhood through early adulthood, and examine how social adversity and cannabis use affect these outcomes.

The main questions that we will address in Work theme 1 of this proposal are:

i) What is the prevalence and incidence rate of psychotic experiences, high-risk mental states, and psychotic disorder at age 24 years?

ii) What proportion of those with psychotic experiences or high-risk mental states at age 18 persist, remit, or transition to psychotic disorder at age 24?

iii) How do trajectories of psychosis using data from ages 12, 18 and 24, relate to changes in social and occupational functioning over this time period, independently of time-varying confounders?

iv) What is the effect of a) social adversity, indexed by measures of childhood maltreatment, harsh parenting, peer- or sibling-victimization or disturbed peer relationships, and b) cannabis use, and changes in these exposures over time, on incident psychotic experiences?

Work theme 2: Cognitive vulnerability. We aim to examine whether (i) cognitive models of psychosis based on deficits found in patients with schizophrenia in relation to source monitoring, reasoning bias and predictive coding are associated with psychotic experiences in the general population, and (ii) whether social adversity and cannabis use are associated with these deficits.

The main questions that we will address in Work theme 2 of this proposal are:

i) Are deficits in cognitive processes relating to source-monitoring, reasoning bias, and predictive coding in young adults associated with psychotic experiences at this age, and are these symptom-specific (as hypothesised for source-monitoring (hallucinations) and reasoning bias (delusions))?

ii) To what extent are associations between these cognitive processes and psychotic experiences independent of intellectual ability, adolescent depression, and other potential confounders?

iii) Are experiences of social adversity and cannabis use during adolescence associated with deficits in these cognitive processes, and to what extent might these deficits explain associations between these environmental exposures and psychotic experiences in young adults?

Work theme 3: Genetic risk. We aim to examine whether genetic risk for schizophrenia, based on risk score profiling, is associated with deficits in the cognitive processes described above, and explore how genetic risk for schizophrenia is manifest in relation to neurocognitive, psychopathological, and social phenotypes from childhood through to young adulthood.

The main questions that we will address in Work theme 3 of this proposal are:

i) Does schizophrenia liability as indexed by risk score predict:

* source-monitoring, reasoning bias or predictive coding performance?

* neurocognition (processing speed, working memory, and verbal and performance IQ)?

* psychopathology (psychotic experiences, negative symptoms, depression, anxiety, and autism spectrum disorder traits)?

* social-environmental stressors (social adversity and cannabis use)?

* reduced social and occupational functioning?

ii) Do patterns of association between risk score and neurocognition and psychopathology differ by developmental stage (childhood (0-12), adolescence (13-18), and early adulthood (19-24))?

iii) How does risk of psychotic experiences at age 24 vary in relation to risk score and co-exposure to social adversity or cannabis use?