Studies using iPS cells from patients with bipolar disorder and schizophrenia have found abnormalities in neuronal morphology common to both diseases.Joint research groups such as Keio University, Sumitomo Dainippon Pharma Co., Ltd., and Nagoya University have revealed.
Although bipolar disorder and schizophrenia are both major psychiatric disorders, the detailed mechanisms leading to their causes and onset have not been clarified.The research group discovered a deletion of the PCDH2018 gene in patients with bipolar disorder, a novel copy number variation (CNV) discovered in 15 that is thought to be involved in the development of these psychiatric disorders. We focused on the deletion of the RELN gene in patients with schizophrenia.
First, from iPS cells derived from patients with each CNV, two types of nerve cells (glutamatergic nerve and GABAergic nerve), which have been pointed out to have decreased function and network disruption in psychiatric disorders, are selectively selected. We have established a method for producing with high efficiency.
As a result, in both types of nerve cells, shortening of dendrites and reduction of the number of synapses were observed in both diseases as compared with nerve cells derived from healthy subjects.It was also found that similar abnormalities were observed in nerve cells prepared from iPS cells in which PCDH2 or RELN was artificially deleted by gene editing technology.That is, it was suggested that this abnormality is a common pathological condition in psychiatric disorders and may be related to the functions of PCDH15 and RELN.
Until now, in psychiatric disorders with complicated genetic backgrounds, the hurdles for research using iPS cells have been high, and even in research using animal models, there was a limit to the reproduction of the disease.On the other hand, the results of this research have succeeded in reproducing the pathological conditions common to typical psychiatric disorders by using patient-derived iPS cells with pathological CNV. It is expected to lead to the development of drugs.
