A Multimodal Approach For Studying Pathways Leading To Psychosis In 22Q11 Deletion Syndrome

Abstract

Overall Abstract 22q11 deletion syndrome (22q11DS), also known as velo-cardio-facial syndrome has been the focus of intensive research over the last 15 years. The syndrome is the most commonly known microdeletion syndrome, occurring in at least 1 to 4,000 live births, and is the most commonly known genetic syndrome associated with schizophrenia, with approximately one-thirds of individuals developing schizophrenia by young adulthood. Thus, 22q11DS provides a homogeneous model from which to learn about the effects of decreased dosage of genes on the development of brain structure and function and consequently on the emergence of schizophrenia-like psychotic disorder. The proposed symposium consists of leading 22q11DS international researchers and clinicians and young Israeli scientists. The presenters study longitudinally large cohorts of children, adolescents and young adults with 22q11.2DS. Dr. Gothelf will provide an introduction on the genetic and medical characteristics of 22q11DS. He will also present data on the genotype-neuropsychiatric phenotype associations in 22q11DS and preliminary findings of elevated levels of neuroinflammatory factors in psychotic 22q11DS individuals. Dr. Gur will describe the common psychiatric comorbidities occurring in two-thirds of individuals with 22q11DS including ADHD, anxiety disorders and psychotic disorders. She will also present longitudinal data following the developmental trajectories of attenuated psychotic symptoms in 22q11DS. Dr. Kates will summarize a twelve-year longitudinal study of neuroanatomic, neurofunctional and neuropsychological development in youth with 22q11.2 deletion syndrome (22q11DS). Dr. Kates identified aberrant longitudinal alterations in cortical thickness / connectivity, as well as neurocognitive deficits that may represent biomarkers for the eventual onset of prodromal psychosis in 22q11DS. Finally Dr. Michaelovsky will present the results of bioinformatics analyses on DNA samples of a unique 22q11.2DS multigeneration family (mother and her four children), including psychotic and non-psychotic subjects.