Converging Biochemical Pathways in Psychiatric Disorders

According to the World Health Organization, neuropsychiatric diseases account for approximately one third of years lost to disability. Yet, despite this huge disease burden, there is a lack of new treatments under development: approved treatments all essentially target the same target(s), if the target itself is known. There is now considerable evidence for a common set of heritable risk for psychiatric disorders including schizophrenia, bipolar disorder, as well as autism. Many of these risk alleles affect genes implicated in neuronal development with known roles at an early stage; these genes would have an effect on the individual before the onset of overt symptoms or diagnosis. Furthermore, many of the genes identified are known to participate in established pathways that are relevant for neuronal development and function. It is important then to address the causality between these signaling pathways that are important for neurodevelopment, and the risk of developing neuropsychiatric disorder. The work presented in this thesis represents two projects that aim to work toward this goal. The first project pertains to the mechanisms of transcriptional repression by DISC1 on ATF4-mediated gene transcription. The second project presents some initial steps towards uncovering the role of BCL9 in neuronal development. Thesis Supervisor: Li-Huei Tsai Title: Picower Professor of Neuroscience, Department of Brain and Cognitive Sciences Director, the Picower Institute for Learning and Memory