Schizophrenia and bipolar disorder (manic depressive illness) are serious psychiatric disorders that develop early in life and may require lifelong treatment. They also cause enormous socio-economic loss as well as the suffering of patients and their families. In many cases, no curative drugs or established diagnostic methods have been developed because the cause and pathophysiology are unknown.
In this lab, we will clarify the causes and pathophysiology of psychiatric disorders through researches focusing on dynamic aspects of the brain genome, such as epigenetics and somatic mutations, using postmortem brain samples and animal models. We will promote researches that can be returned to society, such as early diagnosis methods and establishment of new treatment strategies.
The cause of psychiatric disorders is thought to be the complex interaction of genetic and environmental factors. Understanding of genetic factors has been rapidly advancing in recent years, and from epidemiological studies on environmental factors, pregnancy and perinatal factors, care and nutritional conditions, drug intake and stressful life events increase the risk of developing psychiatric disorders. However, it is largely unclear how genetic and environmental factors interact to lead to the onset.
We hypothesize that the environmental factors act on the genomic DNA of the central nervous system and affect the genetic information, contributing to the causes and pathophysiology of psychiatric disorders. As the molecular mechanisms of gene-environment interaction, we focus "epigenetics" and "somatic mutation".
We study DNA methylation status using postmortem brain samples and cell/animal models, and develop new experimental and bioinformatic technologies for this purpose. We are also investigating the effects of antidepressants and antipsychotics on DNA methylation. To date, we have established a neuronal nuclear fractionation method from brain samples (Genome Res 2011) and elucidated the DNA methylation status of neurons in patients with bipolar disorder (Mol Psychiatry 2021).
We study somatic mutations in postmortem brain samples and cell/animal models, and develop new experimental and bioinformatic technologies for this purpose. Among the various somatic mutations, we are especially focusing on single nucleotide variants, transposon dynamics, and ectopic recombination. To date, we have shown that the number of genomic copies of transposon LINE-1 is elevated in neurons of schizophrenic patients (Neuron 2014).
We are also developing biomarkers for early diagnosis of psychiatric disorders using blood and saliva samples. To date, we have identified DNA methylation status of major candidate genes such as serotonin transporter and BDNF gene, and abnormalities in epigenome-related metabolites. We are also applying our findings to research on gender identity and aging.