Investigation of the brain connectivity patterns associated with psychotic experiences throughout infancy and adolescence and the genetic and environmental modulation

Abstract

Schizophrenia is the most severe psychotic disorder in which environmental and genetic factors act throughout neurodevelopment causing changes in brain connectivity. Although psychotic experiences (PE) are highly prevalent during childhood, it is not known the relationship of PE and brain connectivity during the neurodevelopment. Objective: To investigate how the changes of brain network connectivity are associated with psychotic experiences during childhood and adolescence, and investigate the role of genetic markers and traumatic experiences in this process. Methods: The sample will be composed of 724 subjects that are part of the High Risk Cohort (National Institute of Developmental Psychiatry - CNPq/FAPESP), one of the most important cohorts evaluating brain developmental trajectories of mental disorders worldwide. Baseline and a 3-year follow-up evaluations of PE, structural magnetic resonance imaging (MRI) and resting state functional MRI (rsfMRI) scans, and blood DNA samples. Together with cutting-edge researchers of the Institute of Psychiatry, Psychology and Neuroscience (King's College London) we will develop methodologies to integrate complex data combining cortical thickness (FreeSurfer), Graph Analysis (rsfMRI), genomic analysis (Illumina HumanCore BeadChip 250k), environmental and psychopathological data in two time points. Justification: This study has the unique opportunity to examine biological processes associated with psychosis because of the follow-up design with MRI scans and genetic evaluations in a large community sample of children and adolescents at increased risk to develop psychotic disorders. We are monitoring PE from 7 to 18 years allowing the investigation of the relationship of PE and changes in brain connectivity during neurodevelopment. In collaboration with Prof McGuire (Institute of Psychiatry, Psychology and Neuroscience - IoPPN, King's College London) we have developed cutting-edge methodologies of rsfMRI analyses and have published several highly relevant scientific articles on normal brain connectivity development, and the relationship with general psychopathology. In this project we intend to identify biological and environmental factors that interfere with brain network development and the relationship with PE during crucial phases of the neurodevelopment. To pursue this objective it is necessary to face on of the most important challenges of neuroscience, methodology integration (neuroimaging, genetics, psychopathology and environmental variables). The one-year of research in a reference center such us the IoPPN will be fundamental to tackle this challenge, since I will have full dedication to the project and the opportunity to work very close with some of the most important researchers in the world performing integrative neuroscience with these methodologies. After this period, these new technologies will be implemented in our lab at UNIFESP and in the National Institute of Developmental Psychiatry. Expected Results: We expect that with this approach we will be able to establish measures that are predictive of psychiatric morbidity and that can be used for early recognition and prevention of psychotic disorders. (AU)