Important unanswered questions about adult neurogenesis in schizophrenia

Abstract

Aberrant neurogenesis may contribute to the pathogenesis, pathophysiology and symptoms of schizophrenia. This review summarizes the state of knowledge of adult neurogenesis in schizophrenia and raises important unanswered questions. We highlight how alterations in signalling molecules in the local and peripheral environments in schizophrenia may regulate adult neurogenesis in the human subgranular zone of the hippocampus and the subependymal zone (SEZ). Cell proliferation and density of mature neurons are reduced in the hippocampus, yet the extent of adult neurogenesis remains unexplored in the SEZ in schizophrenia. The human SEZ is a major source of postnatally migrating cortical and striatal inhibitory interneurons, indicating that aberrant neurogenesis may extend to the SEZ and contribute to inhibitory interneuron deficits in schizophrenia. Trophic factors and inflammatory cytokines regulate the generation of new neurons in rodents, suggesting that altered expression of these signalling molecules in the brain, peripheral vasculature and cerebrospinal fluid in schizophrenia may impact adult neurogenesis in both the hippocampus and the SEZ. Knowledge about adult neurogenesis remains scant in schizophrenia. We propose that a more rigorous examination of adult neurogenesis in relation to regulatory signalling molecules will allow us to identify how abnormalities may contribute to the pathophysiology of schizophrenia.