Laboratory for Molecular Dynamics of Mental Disorders

The goal of this team is to clarify the molecular basis of bipolar disorder, one of two major mental disorders, to develop new diagnostic methods and treatments. Mitochondrial dysfunction is suggested to play a role in pathophysiology of bipolar disorder. In this study, animal models, postmortem brains, and patients' genomes are studied. We are aiming at elucidating the neuropathological changes causing bipolar disorder. A possible role of epigenetics in the pathophysiology of mental disorders is suggested/ We will study the role of epigenetics in mental disorder by analyzing postmortem brains of patients and animal models.

Research Subjects

• Elucidation of the neural basis of bipolar disorder
• Epigenetic analysis of mental disorders

Publications

1. Iwamoto, K., Bundo, M., Ueda, J., Oldham, M.C., Ukai, W., Hashimoto, E., Saito, T., Geschwind, D.H., Kato, T.:
   " Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons."
   Genome Research 21: 688-696 (2011).
2. Kubota, M., Kasahara, T., Iwamoto, K., Komori, A., Ishiwata, M., Miyauchi, T., and Kato, T.:
   " Therapeutic implications of down-regulation of cyclophilin D in bipolar disorder."
   International Journal of Neuropsychopharmacology 13: 1355-1368 (2010).
3. Kasahara T, Abe K, Mekada K, Yoshiki A, Kato T.:
   " Genetic variation of melatonin productivity in laboratory mice under domestication."
   Proceedings of the National Academy of Sciences of the United States of America 107: 6412-6417 (2010).
4. Kuratomi, G., Iwamoto, K., Bundo, M., Kusumi, I., Kato, N., Iwata, N., Ozaki, N., and Kato, T.:
   " Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins."
   Molecular Psychiatry 13, 429-441 (2008).
5. Oldham, M.C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., and Geschwind, D.H.:
   " Functional organization of the transcriptome in human brain."
   Nature Neuroscience 11, 1271-1282 (2008).
6. Kato T.:
   " Molecular neurobiology of bipolar disorder: a disease of "mood stabilizing neurons""
   Trends in Neuroscience 31, 495-503 (2008).
7. Kasahara, T., Kubota, M., Miyauchi, T., Noda, Y., Mouri, A., Nabeshima, T., and Kato, T.:
   " Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes"
   Molecular Psychiatry, 11, 577-593 (2006).
8. Kubota, M., Kasahara, T., Nakamura, T., Ishiwata, M., Miyauchi, T., and Kato, T.:
   " Abnormal Ca2+ dynamics in transgenic mice with neuron-specific mitochondrial dna defects"
   Journal of Neuroscience, 26, 12314-24 (2006).
9. Iwamoto, K., Bundo, M., and Kato, T.:
   " Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis"
   Human Molecular Genetics, 14, 241-53 (2005).
10. Kakiuchi, C., Iwamoto, K., Ishiwata, M., Bundo, M., Kasahara, T., Kusumi, I., Tsujita, T., Okazaki, Y., Nanko, S., Kunugi, H., Sasaki, T., and Kato, T.:
    " Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder"
    Nature Genetics, 35, 171-175 (2003).