Molecular Dynamics of Mental Disorders
Senior Team Leader
Bipolar disorder, Mitochondria, Epigenetics
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.
Effect of lithium on altered activity rhythm in bipolar disorder model mice.
Horizontal axis represents time (48 hours) and the vertical axis represents the wheel running activity. When lithium was administered to the mouse showing periodic activity change, this activity change was dissapeared.
Takata A*, Matsumoto N, and Kato T* (* co-corresponding authors): "Genome-wide identification of splicing QTLs in the human brain and their enrichment among schizophrenia-associated loci", Nature Communications, 8, 14519 (2017)
Kataoka M*, Matoba N*, Sawada T, Kazuno AA, Ishiwata M, Fujii K, Matsuo K, Takata A+, Kato T+ (*co-first authors in alphabetical order, and + co-corresponding authors): "Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations", Molecular Psychiatry, 21(7), 885-93 (2016)
Kasahara T*, Takata A*, Kato TM*, Kubota-Sakashita M, Sawada T, Kakita A, Mizukami H, Kaneda D, Ozawa K, and Kato T(*co-first authors) : "Depression-like Episodes in Mice Harboring mtDNA Deletions in Paraventricular Thalamus", Molecular Psychiatry, , 21, 39-48 (2015)
Bundo M, Toyoshima M, Okada Y, Akamatsu W, Ueda J, Nemoto-Miyauchi T, Sunaga F, Toritsuka M, Ikawa D, Kakita A, Kato M, Kasai K, Kishimoto T, Nawa H, Okano H, Yoshikawa T, Kato T, and Iwamoto K: "Increased L1 Retrotransposition in the Neuronal Genome in Schizophrenia.", Neuron, 81(2), 306-13 (2014)
Iwamoto K, Bundo M, Ueda J, Oldham MC, Ukai W, Hashimoto E, Saito T, Geschwind DH, and Kato T: "Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons.", Genome Res, 21(5), 688-96 (2011)
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.", Int J Neuropsychopharmacol, 13(10), 1355-68 (2010)
Kasahara T, Abe K, Mekada K, Yoshiki A, and Kato T: "Genetic variation of melatonin productivity in laboratory mice under domestication.", Proc Natl Acad Sci U S A, 107(14), 6412-7 (2010)
Oldham MC, Konopka G, Iwamoto K, Langfelder P, Kato T, Horvath S, and Geschwind DH: "Functional organization of the transcriptome in human brain.", Nat Neurosci, 11(11), 1271-82 (2008)
Kato T: "Molecular neurobiology of bipolar disorder: a disease of 'mood-stabilizing neurons'?", Trends Neurosci, 31(10), 495-503 (2008)
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)
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.", J Neurosci, 26(47), 12314-24 (2006)
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.", Mol Psychiatry, 11(6), 577-93 (2006)
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.", Hum Mol Genet, 14(2), 241-53 (2005)
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.", Nat Genet, 35(2), 171-5 (2003)
- Oct. 20, 2015 First mouse model of spontaneous depression-like episodes Tadafumi Kato, M.D., Ph.D., Molecular Dynamics of Mental Disorders
- Jan. 3, 2014 Jumping DNA in the brain may be a cause of schizophrenia Tadafumi Kato, M.D., Ph.D., Molecular Dynamics of Mental Disorders
- Aug. 11, 2006 Variability in genes outside the nucleus linked to longevity Tadafumi KATO, M.D., Ph.D., Molecular Dynamics of Mental Disorders
- Apr. 18, 2006 Mitochondrial dysfunction contribution to bipolar disorder confirmed using model mice Tadafumi KATO, M.D., Ph.D., Molecular Dynamics of Mental Disorders