Biology of schizophrenia: Is treatment refractoriness synonymous with severity of illness [A.K.A. is this a drug efficacy problem or an expression of severe illness?

Approximately one-quarter of individuals develop schizophrenia in early childhood and adolescence. Typically, the course of illness in these patients is deteriorative. Moreover, longitudinal evaluation of chronic relapsing illness reveals evidence of neurodegenerative tissue loss. There is some evidence-albeit preliminary and somewhat controversial-that antipsychotic medications can obviate and/or ameliorate these changes. This chapter will describe the neurobiology of schizophrenia with a focus on the timing, evolution, and putative neurobiological correlates of treatment-refractoriness in schizophrenia.