The Role of Childhood Onset Schizophrenia and Epilepsy Genes in the Brain and Behavior

Abstract

Schizophrenia and epilepsy are chronic neurological disorders. Schizophrenia afflicts about one percent of the population and is characterized by degeneration of thinking, motor and emotional processes. Epilepsy, a disorder defined by recurrent seizures, also affects one percent of the population. Recent epidemiological and genetic studies have revealed a bidirectional link between epilepsy and schizophrenia. While the symptoms of epilepsy and schizophrenia such as seizures, hallucinations and behavioral regression are widely recognized, their causes are not well understood. By examining the genetic overlap between the two diseases focusing on childhood onset schizophrenia, we hoped to better understand phenotypic abnormalities in both disorders. We used CRISPR/Cas technology to create genetic knockouts of genes (pdxdc1, kcnq3, and pcdh19) associated with either or both diseases in zebrafish (Danio rerio). We assessed the neural activity of our knockout zebrafish through phosphorylated extracellular-regulated kinase (pERK) brain imaging and conducted behavioral tests. Mutants exhibited phenotypes that included altered forebrain and hindbrain activity, and decreased PPI. Overall, we identified variable phenotypic abnormalities for each gene mutant that can be used to eventually model epilepsy and schizophrenia.