ABSTRACT

Introduction It is unclear which of the inhabitants of gray matter (neuronal bodies and dendrites, glia, and the blood vessels) contribute to volume losses in schizophrenia, and whether they “die out”. First, substantial data provide evidence for reduced gray matter volumes in schizophrenia across a wide range of brain regions. Second, longitudinal imaging studies suggest that the gray matter losses are not only seen before and early in the course of the illness, but also continue to progress during the chronic phases of the illness, contributing to clinical worsening. Third, neuropathological evidence points to reductions in glial numbers, neuronal somal volume and dendrite density, but not neuronal loss. Finally, clinical studies are inconclusive about whether antipsychotics contribute to or mitigate gray matter loss in schizophrenia. The absence of reduced neuronal numbers may suggest the benefit of hypothesis-driven pharmacological and cognitive remediations on neuroplasticity. Reassuringly, while the neuronal inhabitants of gray matter may be moribund, they may at least in part be revived with appropriate therapeutic interventions.