Scientific basis: Symptoms of schizophrenia and related psychotic disorders are currently understood to exist on a continuum from health to (psychotic) illness. Schizotypy describes a set of multidimensional traits in the general population associated with heightened risk for schizophrenia. Hence, the study of schizotypy may inform both mechanisms of risk for schizophrenia as well as potential resilience factors, without confounding by antipsychotic medications or psychiatric comorbidities.
Our recent findings from the world’s largest MRI study in schizotypy (n>3,000 individuals) by the ENIGMA Schizotypy consortium (led by Prof. Modinos) identified that higher schizotypy traits are associated with higher cortical thickness. These cortical thickness differences were greatest in individuals who had been exposed to high levels of childhood trauma (abuse and neglect), a well-known risk factor for schizophrenia (OR=2.8). However, the relationship between schizotypy and functional connectivity patterns, enabling understanding complex neurobiology from an integrative perspective rather than studying brain volumes separately, and the moderating effects of childhood trauma on these patterns, remains to be explored. Moreover, childhood trauma in the form of abuse and neglect is associated with distinct clinical manifestations in people with a psychotic disorder and in clinical high-risk individuals. For example, while abuse tends to be associated to positive symptoms, for the negative symptoms neglect seems to be the only trauma subtype that is relevant, suggesting distinct underlying mechanisms. The project will thus also explore how childhood trauma subtypes can shape the relationships between different schizotypy trait domains and functional connectivity.
Techniques and skills: Theoretical background of schizotypy/schizophrenia and childhood trauma, statistical analysis of large-scale functional and structural neuroimaging data and associations with symptoms and trauma, dissemination. The student will also develop valuable transferrable skills through e.g., working in an international consortium.
Aims: This PhD project will (1) Determine functional connectivity patterns related to schizotypy traits levels in the ENIGMA Schizotypy large-scale dataset; (2) Examine the moderating effects of childhood trauma and its sub-types on these relationships, and (3) Apply a novel approach (regional vulnerability index, RVI) to quantify the similarity between an individual schizotypy brain pattern and the expected brain pattern of schizophrenia. The results may provide biomarkers to help identify individual levels of psychosis risk across the psychosis continuum.
Overarching objectives:
– Y1: Training, neuroimaging analysis pipeline development, preliminary analyses.
– Y2: Functional connectivity analyses in schizotypy and moderation by childhood trauma.
– Y3: RVI analyses for individual risk prediction.
– Y4: Final data analysis, thesis write-up, conference presentation and journal publications.