Genetics and Neuroimaging in Schizophrenia

Abstract

Schizophrenia is a highly heritable disorder characterized by disruptions on the molecular, cellular, and neural circuit level that lead to the behaviors and cognitive impairments associated with the illness. This chapter evaluates how combining neuroimaging methods with genetic approaches such as studying single genes and polygenic risk scores, to genome-wide association study (GWAS) variants and gene expression networks, can provide valuable insight into both biomarkers of schizophrenia and underlying neural mechanisms. Discussions begin with the evolving focus on smaller studies and a few genetic variants to larger scale multi-variant initiatives, and the benefits and challenges of both. The implications of recent findings are explored from bottom-up studies investigating brain abnormalities associated with candidate and GWAS identified variants individually, as well as the utility of examining aggregated risk in the form of polygenic risk scores. Advancements with large collaborative efforts such as ENIGMA hold promise with their top-down work identifying genetic variants underlying variation in brain structure, function, and connectivity. However, further work is needed to clarify how this builds upon our knowledge of intermediate phenotypes and insight into schizophrenia pathology. Moving forward, this chapter highlights emerging work examining relationships between imaging phenotypes and gene expression patterns that take into account spatial variation across the brain. It also evaluates the importance and increasing prevalence of studies investigating schizophrenia from a neurodevelopmental standpoint, and provides a dimensional point of view by examining early and prodromal stages of psychosis. Finally, the overall limitations in imaging genetic research, including challenges, and the progress to overcome them are discussed.