Understanding the neurobiological effects of copy number variants (CNVs) that predispose to neuropsychiatric disorder is key to disentangling the complex associations between genes and behavior. As one of the most highly penetrant CNVs associated with schizophrenia, the 22q11.2 microdeletion provides a unique window into these complex relationships. In this talk I will focus on the latest results from our large-scale prospective patient cohort studies, structural and functional neuroimaging findings, and collaborative work from animal and human induced pluripotent stem cell models (Pasca et al, 2015). These integrative approaches have facilitated our understanding of the impact of this microdeletion on cells, circuits and systems that contribute to pathological behavior. Collectively, these studies converge on a set of neurobiological pathways by which the microdeletion may lead to cognitive and psychiatric phenotypes, and suggest convergent mechanisms between microdeletion-associated and idiopathic schizophrenia.
