Adult Neurogenesis in Neuropsychiatric Disease

Lay Summary

Altered production and migration of new brain cells may contribute to psychiatric diseases

Investigators will study whether excessive development and altered migration of new neurons in the brain contributes to schizophrenia and to other psychiatric disorders.

Scientists have established that the brain continues to make new neurons throughout life, through a process called neurogenesis. Neural stem cells (called neuroblasts) reside in a region located toward the back of the brain, called the subependymal zone (SEZ).  When the brain needs new cells, the neuroblasts migrate into the olfactory bulb, a region that facilitates the sense of smell.  Here the neuroblasts mature into neurons and then migrate into other brain areas that need them. Ordinarily, neural stem cell activation in the SEZ is regulated, at least in part, by “ependymal” cells that are located just above the SEZ.

Recently, investigators found preliminary evidence in autopsy studies of brain tissues from deceased schizophrenia patients that regulatory ependymal cells are reduced and neurogenesis is increased. Similarly, increased neurogenesis has been observed in autopsied brain tissues from patients who had died following Alzheimer’s and Huntington’s disease, both of which have psychiatric aspects. Moreover, a number of genes and molecules that affect neurogenesis have been implicated in psychiatric disorders. Signaling disruptions in several neurotransmitters, for instance, are seen both in psychiatric diseases and in disorders that affect adult neurogenesis. Additionally, olfactory deficits occur both in schizophrenia and Alzheimer’s disease. These findings suggest a link between adult neurogenesis and psychiatric diseases. Additional evidence suggests that maintenance of normal neurogenesis is necessary for anti-depressive medication effectiveness.

Based on these related factors, the investigators hypothesize that the adult SEZ and neurogenesis are altered in psychiatric diseases, and that alterations may occur differently in different psychiatric diseases, potentially serving as biomarkers for testing treatments. They will explore these hypotheses by studying neurogenesis in autopsied brain tissues from patients who had schizophrenia and compare them to autopsied tissues of three other categories: patients who had unipolar depression, bipolar disease, or no psychiatric disease. The study must be undertaken in brain tissues because current techniques, including MRI, cannot adequately show stem cell neurogenesis in living people.  They will measure the integrity and density of ependemyal cells, and of the cells involved in neurogenesis, and determine whether altered regulation, development, and migration occurred and whether these differences vary among the three psychiatric diseases.

Significance: If this study identifies how altered neurogenesis occurs and varies among schizophrenia, unipolar depression, and bipolar disease, the findings could produce new biomarkers that could be used to test new therapeutic agents for each.