Untitled

Chapter 5Transcriptional Regulationin SchizophreniaScott E. Hemby and Joann A. O’ConnorTranscription refers to the synthesis of messenger RNA (mRNA) from genomicDNA within the nucleus of cells. After processing in the nucleus and transportinto the cytoplasm, mRNA serves as the direct template for protein synthesis, aprocess referred to as translation. Biological processes are regulated at the levelof transcription throughout the course of human development. Maturationalchanges in transcription/gene expression are regulated in response to hormonal,behavioral, pharmacological, pathogenic, and developmental influences. Assessmentof gene expression in animal models or human specimens—serum, CSF, orpostmortem brain tissue—provides a biochemical window through which potentialbiochemical substrates or consequences of psychiatric illnesses are identified.Although this chapter is primarily focused on transcriptional regulation in schizophrenia,the processes described are also relevant to other psychiatric disorders.Psychiatric diseases such as schizophrenia and autism spectrum disorders aregenerally considered to be neurodevelopmental in origin. Dysregulated gene and/or protein expression in the brain of adult schizophrenic patients must be understoodin the context of a developmental model. Do changes in gene expressionoccur at the time of disease vulnerability or before (i.e., in utero, childhood, adolescence)?Are they present in high-risk individuals? Current understanding ofthe transcriptional sequelae that occur during brain development is limited by theavailability of control human brain tissue in children and adolescents. Conse-103