Introduction

Emil Kraepelin, one of the founding fathers of the diagnostic concept of schizophrenia, argued that the disorder was underpinned by abnormalities in brain structure. In his 1899 textbook, Kraepelin wrote: “in dementia praecox [schizophrenia], partial damage to, or destruction of, cells of the cerebral cortex must probably occur” (Kraepelin,1907). Since that time, an enormous amount of research has been undertaken with an eye to determining whether or not Kraepelin was correct. Until recently, the question of whether patients with schizophrenia (SZ) exhibit abnormalities in brain structure was more or less synonymous with the question of whether they exhibit abnormalities in gray matter (GM). The GM, so-called because of its grayish appearance in post-mortem tissue sections, is thought to consist primarily of neuron bodies, dendrites, axon terminals and other synaptic infrastructure and certain classes of neuroglia. Until recently, the vast majority of research aimed at investigating the neuroanatomical underpinnings of SZ has focused on GM. This is perhaps understandable, given that GM comprises both the brain's fundamental units of information processing (neurons) and the sites-of-action for most psychotropic medications (synapses). In recent years, however, a growing proportion of contemporary research has begun to focus on the “other half of the brain” (as wryly denoted by Fields, 2004), i.e. the white matter. The white matter (WM) is primarily constituted of myelinated axon sheaths, which form the infrastructure for signal transmission between spatially discrete populations of neurons.