An inter-institutional team using state-of-the-art stem-cell technology has bolstered evidence that schizophrenia begins to take shape in the womb even though full-blown symptoms of the disorder usually don’t appear until adolescence or early adulthood.
The research was supported in part by a 2013 NARSAD Distinguished Investigator Grant to Fred H. Gage, Ph.D., of the Salk Institute and was published online on April 1st in the journal Molecular Psychiatry. The study was co-designed by Dr. Gage and Kristen Brennand, Ph.D., of the Icahn School of Medicine at Mount Sinai, and 2013 NARSAD Young Investigator Grantee Kazue Hashimoto-Torii, Ph.D., of Yale University and the Children’s National Medical Center, also participated in the research.
In the study, skin cells from four patients with schizophrenia and six healthy control subjects were converted into stem cells called neural progenitor, or precursor, cells (NPCs), which are comparable to fetal brain cells destined to mature into neurons. The objective of the study was to look for the earliest changes in these cells that could affect brain development and be linked to schizophrenia. The authors explain that although postmortem studies of brains of people with schizophrenia have identified defects in neurons, “these findings represent disease end points and reveal little about disease predisposition or initiation.”
The research showed that the NPCs from the schizophrenia patients behaved differently from the NPCs from the controls in migration and cell adhesion patterns, processes important in making appropriate connections in building the brain. The patients’ NPCs also showed increased levels of oxidative stress, which can lead to cell death.
Although the sample in the study was small, the researchers believe that their approach can be applied to expanded numbers of patients, making NPCs potentially valuable tools with which to study the developmental mechanisms that contribute to schizophrenia. Revealing that they were “surprised at how early in the developmental process that defects in neural function could be detected," Dr. Gage states that the study “hints that there may be opportunities to create diagnostic tests for schizophrenia at an early stage."