Studying psychiatric diseases using quantitative susceptibility mapping (QSM)

Quantitative Susceptibility Mapping (QSM), a sophisticated MRI-based technique for quantifying brain magnetic susceptibility, has emerged as a valuable tool in exploring neurodegenerative diseases and, more recently, psychiatric disorders such as first-episode schizophrenia, depression, anxiety, and stress. This method allows the measurement of magnetic susceptibilities in various tissues, unveiling associations with diverse phenotypes like body iron, blood assays, diet, and alcohol consumption. Furthermore, investigations into genetic variations across the genome have revealed intriguing links between magnetic susceptibility and clusters of genes responsible for crucial biological functions, including iron regulation, calcium mechanisms, myelin development, and the extracellular matrix.Our primary objective in this thesis is to study associations between psychiatric illnesses and iron content in the gray matter nucleus utilizing QSM. In pursuit of this goal, we conducted two comprehensive analyses involving cohorts of first-episode psychosis patients from Chile and individuals with psychotic-like experiences from the UK biobank. The study scrutinized QSM and R2* differences in gray brain nuclei between patients and controls, employing linear mixed models to explore associations with demographic and clinical variables and genetic factors. Notably, the incorporation of polygenic risk scores (PGS) for psychotic-like experiences in our statistical analyses yielded significant differences in QSM and R2∗ rates between patients and control subjects. Organized into six chapters, our thesis begins with an introduction to the characteristics of psychotic diseases and image biomarkers. Subsequent chapters delve into the theoretical framework linking psychiatric disorders with magnetic susceptibility, detail the methodology employed, present the results, discuss the findings, and conclude with overarching insights. Our findings demonstrate that QSM serves as a powerful tool that may help to elucidate the neurophysiological processes in psychosis and their relationship with iron metabolism. Finally, the proposed methods contribute valuable insights to our current understanding and offer promising image biomarkers for ongoing and future psychiatric research.