Changes in Gene Expression in Subjects with Schizophrenia Associated with Disease Progression

Abstract

Schizophrenia is increasingly recognised as a progressive disorder because the central nervous system (CNS) structure, symptom profile and drug requirements vary with the duration of illness. Changes in gene expression and subsequent levels of CNS protein are likely to underlie the progressive changes in CNS function in schizophrenia. This chapter will review evidence that supports the notion that differential changes in gene expression with duration of illness does occur in the CNS of subjects with schizophrenia. Moreover, the temporal nature of these changes suggests that they may contribute to changes in drug treatment that occurs in the middle years of the disorder. It will be argued that some of the changes in gene expression in the CNS of subjects with schizophrenia may be associated with a differential aging/maturation processes and, that there are fewer differences in gene expression in subjects with schizophrenia of long duration compared to age-sex matched controls than are apparent between subjects with schizophrenia of short duration and their age-sex matched controls. Schizophrenia is a complex disorder and a further understanding of how temporal changes in gene expression contribute to the pathophysiology of the illness is likely to underpin a better understanding of the changes in CNS structure, symptom profile and treatment regimes that have been associated with the disorder.