Laboratory for Molecular Psychiatry

Endogenous or functional psychoses, such as developmental disorders including autism spectrum disorders and adult-onset disorders (e.g.schizophrenia and mood disorders), are relatively common diseases that show a chronic course. Once the disease develops, the patient’s quality of life deteriorates substantially. This is because there are no ideal medical treatments, a reflection of the largely unknown etiology of these illnesses.

Considering the immense personal and social loss induced by mental disorders, it is imperative to identify the mechanisms of the diseases, so as to develop fundamental therapies and effective prevention.

Our current efforts focus on strategies that aim to identify susceptibility genes and biological mechanisms for psychiatric disorders, by employing molecular and behavioral genetic approaches and other manifold analyses that utilize both human samples and animal models. We hope that these endeavors will lead to a better understanding of neuropsychiatric diseases at the molecular level and eventually contribute to improving the welfare of patients suffering from these disorders.

Research Subjects

• Genetic analyses of schizophrenia, mood disorders and autism
• Studies on animal models (transgenic and knock out mice, and environmental factors)
• Studies using iPS cells stemmed from psychiatric patients
• Studies of the roles of lipids in the pathophysiology of mental illnesses

Publications

1. Takat,a A., Iwayama, Y., Fuku,o Y., Ikeda, M., Okochi, T., Maekawa, M., Toyota, T., Yamada, K., Hattor,i E., Ohnishi, T., Toyoshima, M., Ujike, H,, Inada, T., Kunugi, H., Ozaki, N., Nanko, S., Nakamura, K., Mori, N., Kanba, S., Iwata, N., Kato, T., Yoshikawa, T.:
   "A population-specific uncommon GRIN3A R480G variant associated with schizophrenia"
   Biological Psychiatry 2012 Dec 10. [Epub ahead of print]
2. Toyosima, M., Maekawa, M., Toyota, T., Iwayama, Y., Arai., M, Ichihkawa, T., Miyashita, M., Arinami, T., Itokawa, M., Yoshikawa, T.:
   "A patient with 22q11.2 deletion who developed schizophrenia with additional genetic defects in GLO1 and PHOX2B"
   Br. J. Psychiatry 199, 245-246 (2011)
3. Arai, M,, Yuzawa, H., Nohara, .I, Ohnishi, T., Obata, N., Iwayama, Y., Haga, S., Toyota, T., Ujike, H., Ichikawa, T., Tanaka, Y., Furukawa, A., Aikawa, Y., Kuroda, O., Niizato, K., Izawa, R., Nakamura, K., Mori, N., Matsuzawa, D., Hashimoto, K., Iyo, M.,:
   "Enhanced carbonyl stress in a subpopulation of schizophrenia"
   Archives of General Psychiatry 67, 598-607 (2010)
4. Watanabe, A., Toyota, T., Owada, Y., Hayashi, T., Iwayama, Y., Matsumata, M., Ishitsuka, Y., Nakaya, A., Maekawa, M., Ohnishi, T., Arai, R., Sakurai, K., Yamada, K., Kondo, H., Hashimoto, K., Osumi, N., Yoshikawa, T.
   "Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype"
   PLoS Biology 5, e297 (2007)
5. Yamada, K., Gerber, D.J., Iwayama, Y., Ohnishi, T., Ohba, H., Toyota, T., Aruga, J., Minabe, Y., Tonegawa, S., Yoshikawa, T.:
   "Genetic analysis of the calcineurin pathway identifies the EGR family and specifically EGR3, as potential candidates in schizophrenia"
   Proc. Natl. Acad. Sci. USA 104, 2815-2820 (2007)
6. Nakatani, N., Hattori, E., Ohnishi, T., Dean, B., Iwayama, Y., Matsumoto, I., Kato, T., Osumi, N., Higuchi, T., Niwa, S., Yoshikawa, T.:
   "Genome-wide expression analysis detects eight genes with robust alterations specific to bipolar I disorder: relevance to neuronal network perturbation"
   Hum. Mol. Genet. 15, 1949-1962 (2006)
7. Yamada, K., Ohnishi, T., Hashimoto, K., Ohba, H., Iwayama-Shigeno, Y., Toyoshima, M., Okuno, A., Takao, H., Toyota, T., Minabe, Y., Nakamura, K., Shimizu, E., Itokawa, M., Mori, N., Iyo, M. Yoshikawa. T.:
   "Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels"
   Biol. Psychiatry 57. 1493-1503 (2005)
8. Toyota, T., Yoshitsugu, K., Ebihara, M., Yamada, K., Ohba, H., Fukasawa, M., Minabe, Y., Nakamura, K., Sekine, Y., Takei, N., Suzuki, K., Itokawa, M., Meerabux, J.M.A., Iwayama-Shigeno, Y., Tomaru, Y., Shimizu, H., Hattori, E., Mori, N., and Yoshikawa, T.:
   "Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B"
   Hum. Mol. Genet. 13, 551-561 (2004)
9. Itokawa, M., Yamada, K., Yoshitsugu, K., Toyota, T., Suga, T., Ohba, H., Watanabe, A., Hattori, E., Shimizu, H., Kumakura, T., Ebihara, M., Meerabux, J.M.A., Toru, M., and Yoshikawa, T.:
   "A microsatellite repeat in the promoter of the NMDA receptor 2A subunit (GRIN2A) gene suppresses transcriptional activity and correlates with chronic outcome in schizophrenia"
   Pharmacogenetics 13, 271-278 (2003).
10. Yoshikawa, T., Watanabe, A., Ishitsuka, Y., Nakaya, A., and Nakatani, N.:
    "Identification of multiple genetic loci linked to the propensity for behavioral despair in mice"
    Genome Research 12, 357-366 (2002)