ABSTRACT
There is little question that brain structure and function are abnormally affected in schizophrenia independent of the effects of antipsychotic medications. Many studies using high resolution magnetic resonance imaging (MRI) have consistently found increased ventricular volume, and reduced cortical and subcortical volumes in various brain regions very early in the illness, before any exposure to antipsychotic drugs (1-3). Likewise, abnormal patterns of brain activation in unmedicated schizophrenia patients, carefully matched for task performance, have been reported with positron emission tomography (PET) and functional MRI techniques (4-6). Whether these activation abnormalities are traits of the illness or states related to clinical exacerbations of some components of the disorder is less clear. To characterize systematic brain changes directly linked to antipsychotic drugs, these trait and state illness-related effects must be considered. Antipsychotic medications, the mainstay of the modern treatment for schizophrenia, have been found to be reliably efficacious in improving psychotic symptoms. These agents also have the propensity to induce neuromotoric side effects, hence their original term neuroleptic (“to seize the neuron”). Not surprisingly, neurobiological correlates for both the beneficial and deleterious neuromotoric effects have been identified with neuroimaging techniques. With the introduction over the past decade of atypical antipsychotic agents, effective medications that are less likely to induce extrapyramidal side effects, a variety of studies have attempted to identify the structural and functional brain correlates of the antipsychotic and the extrapyramidal effects. In this chapter we present a selective review of the literature addressing these important issues. A general overview of findings from studies utilizing the following methodologies will be discussed: MRI, magnetic resonance spectroscopy (MRS), functional MRI (fMRI), magnetoencephalography (MEG), and PET (glucose metabolism, blood flow, and receptor ligand).
