2024-05-14

081_ The influence of protective and risk factors on psychotic-like experiences in healthy individuals and psychotic symptoms in patients with schizophrenia

Research Question and Aims

State oft the art:
The assumption of a temporal and phenomenological continuum of psychosis has led to the investigation of "psychotic-like experiences" (PLEs) in the general population in recent years (1). With a prevalence of 7.2% in the general population, PLEs represent a significant phenomenon (2) and increase the risk of developing psychosis, other mental and physical illnesses, suicidality and lead to a reduced subjective quality of life (3, 4, 5, 6). At the end of the psychosis continuum is schizophrenia, which is less common, with a prevalence of about 1.4%, but is associated with substantial impact on life (7, 8). Various factors have been identified as influencing both PLEs and schizophrenia. There is evidence that certain personality traits may both influence the occurrence of PLEs and psychotic symptoms. In particular, higher levels of neuroticism appear to be directly related to the occurrence of psychotic symptoms, as do higher levels of openness and lower levels of extraversion (9). In addition, cannabis and tobacco use have been reported in the literature as independent predictors of PLEs (10, 11, 12). There is also an interaction between the Polygenic Risk Score for Schizophrenia (PRS-Sz) and PLEs in healthy individuals (13). Childhood trauma and a family history of psychiatric illness play a role in the development of psychosis (7, 14, 15). The 2021 discovered "polygenic resilience score" may also be of interest in this context and will be investigated in the analysis of factors influencing both PLEs and schizophrenia (16). There is currently no analysis comparing these factors for both PLEs in healthy controls and psychotic symptoms schizophrenia in a statistical model.

Objective:
We aim to investigate whether and to what extent potential influencing factors such as personality traits, cannabis and tobacco consumption, as well as PRS-Sz, PRS Resilience, noticeable family history, and childhood trauma influence PLEs (measured by the Comprehensive Assessment of Psychotic Experiences (CAPE-42)) in healthy individuals and psychotic symptoms in patients with schizophrenia (measured by the Positive and Negative Syndrome Scale (PANSS)). The PsyCourse dataset provides a unique opportunity to analyze and compare the effects of all these factors together in one single model. A better understanding of the factors that influence psychotic symptoms at the beginning and end of the psychosis continuum could improve both prevention and early recognition of psychosis.

Analytic Plan

Research Question 1:
We want to explore the influence of protective factors (PRS Resilience, inconspicuous family history) and risk factors (tobacco use, cannabis use, childhood trauma (cut-off total), Big Five openness and neuroticism, PRS Schizophrenia) on PLEs (CAPE-42) in a group of healthy controls.
br> Research Question 2:
We want to explore the influence of protective factors (PRS Resilience, inconspicuous family history) and risk factors (tobacco use, cannabis use, trauma (cut-off total), Big Five Openness and Neuroticism, PRS Schizophrenia) on psychotic symptoms differs (PANSS) in a group of patients with schizophrenia.

Research Question 3:
We want to compare the influence of protective factors (PRS Resilience, inconspicuous family history) and risk factors (tobacco use, cannabis use, trauma (cut-off total), Big Five Openness and Neuroticism, PRS Schizophrenia) on PLEs in healthy individuals or respectively psychotic symptoms in patients with schizophrenia. Participants
Data from healthy individuals (Control Group) and patients with Schizophrenia from the PsyCourse who have completed the CAPE- 42 or the PANSS will be included in this study.
Analytic methods for Research Question 1: Method:
multiple linear regression with standardized variables, comparison of effect sizes
Dependent variables: psychotic experiences measured with CAPE-42 (positive, negative and affective subscale)
Independent Variable: personality traits, cannabis use, tobacco use, Childhood Trauma (CTS) and PRS for schizophrenia, PRS for resilience, family history
<>Covariate: age, sex, ancestry principal components
First, we will calculate a multiple linear regression baseline model without PRS. Second, we add the PRS for resilience and separately the PRS for schizophrenia. By adding the PRSs to the models, we aim to reduce the residuals.

Analytic methods for Research Question 2:
Method: multiple linear regression with standardized variables, comparison of effect sizes Dependent variables: Psychotic symptoms in schizophrenia patients with PANSS (positive, negative and general subscale) Independent Variable: personality traits, cannabis use, tobacco use, Childhood Trauma (CTS) and PRS for schizophrenia, PRS for resilience, family history
Covariate: age, sex, ancestry principal components, medication

First, we will calculate a multiple linear regression baseline model without PRS. Second, we add the PRS for resilience and separately the PRS for schizophrenia. By adding the PRSs to the models, we aim to reduce the residuals.

Analytic methods for Research Question 3:
Comparison of the model performance (by the coefficients of determination), comparison of parameters (estimated standardized regression coefficients) from Research Question 1 and 2, Multigroup structural equation modeling

Resources needed

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