Senior Team Leader
Schizophrenia, Autism, Genetics and lipids
Autism spectrum disorders (ASD) and adolescence/adult-onset endogenous psychoses, such as schizophrenia and mood disorders, are relatively common diseases that show a chronic course. Once these diseases develop, the patients' quality of life deteriorate 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 losses 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 genetic and environmental mechanisms, by employing molecular and behavioral genetic approaches and biochemical 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.
Utility of scalp hair follicles as a novel source of biomarker genes for psychiatric illnesses.
In upper panel, the procedure is illustrated. In bottom panel, immunostaining pattern of FABP4, a surrogate marker for schizophrenia, in a hair follicle is shown. FABP4 is co-expressed with K71 in the IRS (inner root sheath) cuticle layer, and displays partially overlapping expression with K85 in the cuticle, matrix/precortex and mid/upper cortex.
However, FABP4 shows scant co-expression with K14, in the ORS (outer root sheath) layer. These results indicated that FABP4 is expressed in the IRS and part of the hair cortex.
Maekawa M, Watanabe A, Iwayama Y, Kimura T, Hamazaki K, Balan S, Ohba H, Hisano Y, Nozaki Y, Ohnishi T, Toyoshima M, Shimamoto C, Iwamoto K, Bundo M, Osumi N, Takahashi E, Takashima A, and Yoshikawa T: "Polyunsaturated fatty acid deficiency during neurodevelopment in mice models the prodromal state of schizophrenia through epigenetic changes in nuclear receptor genes", Translational Psychiatry, in Press (2017)
Gerstner JR, Perron IJ, Riedy SM, Yoshikawa T, Kadotani H, Owada Y, Hans P.A. Van Dongen HPA, Galante R, Dickinson J, Yin JCP, Pack AI, and Frank MG: "Normal sleep requires the astrocyte brain-type fatty acid binding protein FABP7", Science Advances, 3, e1602663 (2017)
Sugiura L*, Toyota T, Matsuba-Kurita H, Iwayama Y, Mazuka R, Yoshikawa T*, and Hagiwara H( *Co-corresponding authors): "Age-dependent effects of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism on language function in developing children.", Cerebral Cortex, 27, , 104-116 (2016)
Toyoshima M, Akamatsu W, Okada Y, Ohnishi T, Balan S, Hisano Y, Iwayama Y, Toyota T, Matsumoto T, Itasaka N, Sugiyama S, Tanaka M, Yano M, Dean B, Okano H, and Yoshikawa T: "Schizophrenia patient-derived induced pluripotent stem cells exhibit changes in neurogenic and gliogenic competences. ", Translational Psychiatry, 6, e934 (2016)
Maekawa M, Yamada K, Toyoshima M, Ohnishi T, Iwayama Y, Shimamoto C, Toyota T, Nozaki Y, Balan S, Matsuzaki H, Iwata Y, Suzuki K, Miyashita M, Kikuchi M, Kato M, Okada Y, Akamatsu W, Mori N, Owada Y, Itokawa M, Okano H, and Yoshikawa T: "Utility of Scalp Hair Follicles as a Novel Source of Biomarker Genes for Psychiatric Illnesses.", Biol Psychiatry, 15(78(2)), 116-25 (2015)
Shimamoto C, Ohnishi T, Maekawa M, Watanabe A, Ohba H, Arai R, Iwayama Y, Hisano Y, Toyota T, Toyoshima M, Suzuki K, Nakamura K, Mori N, Shirayama Y, Owada Y, Kobayashi T, and Yoshikawa T: "Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies.", Hum Mol Genet , 23(24), 6495-6511 (2014)
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), 306-313 (2014)
Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, Kawaguchi T, Tsunoda T, Watanabe M, Takeda A, Tomiyama H, Nakashima K, Hasegawa K, Obata F, Yoshikawa T, Kawakami H, Sakoda S, Yamamoto M, Hattori N, Murata M, Nakamura Y, and Toda T: "Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease.", Nat Genet, 41(12), 1303-7 (2009)
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, and Yoshikawa T: "Fabp7 maps to a quantitative trait locus for a schizophrenia endophenotype.", PLoS Biol, 5(11), e297 (2007)
Yamada K, Gerber DJ, Iwayama Y, Ohnishi T, Ohba H, Toyota T, Aruga J, Minabe Y, Tonegawa S, and Yoshikawa T: "Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia.", Proc Natl Acad Sci U S A, 104(8), 2815-20 (2007)
- Nov. 2, 2016 Schizophrenic stem cells do not differentiate properly into neurons Takeo Yoshikawa, M.D., Ph.D., Molecular Psychiatry
- Sep. 12, 2014 Predicting mental illness with hair follicles Takeo Yoshikawa, M.D., Ph.D., Molecular Psychiatry
- Jul. 15, 2014 Defects in fatty acid transport proteins linked to schizophrenia and autism Takeo Yoshikawa, M.D., Ph.D., Molecular Psychiatry
- Feb. 20, 2007 Joint research between Molecular Psychiatry of BSI and the RIKEN-MIT Neuroscience Research Center has identified genes causative to schizophrenia Takeo YOSHIKAWA, M.D., Ph.D., Molecular Psychiatry, Susumu Tonegawa, Ph.D., RIKEN-MIT Center for Neural Circuit Genetics