Psychiatry

March 1982:

Graduated from Nagoya University School of Medicine.

March 1990:

Got the Degree of Medical Science at Nagoya University School of Medicine.

July 1990:

Visiting Fellow, Clinical Psychobiology Branch, National Institute of Mental Health.

September 1995:

Assistant Professor, at department of Psychiatry, Fujita Health University School of Medicine.

March 1998:

Professor and Chairman, at department of Psychiatry, Fujita Health University School of Medicine.

October 2003:

Professor and Chairman, at department of Psychiatry, Nagoya University Graduate School of Medicine

Elucidation of Pathophysiology of Mental Disorders

The prevalence of mental disorders including schizophrenia, mood disorders, anxiety disorders and substance-related disorders is quite high. These disorders can cause serious social burdens such as suicide and absenteeism in school and workplace. In addition, there are still many treatment-resistant patients with the mental disorders who are although various types of psychotropics have been introduced into clinical settings. Therefore, in order to solve the treatment-resistance we have been trying to elucidate the pathophysiology of the mental disorders as follows.

We identified an uncommon coding region serotonin transporter (SERT) mutation, Ile425Val, in two unrelated families with anxiety disorders. The four most clinically affected individuals-the two probands and their two sibs-had the I425V SERT gene gain-of-function mutation, resulting in faster re-uptake and subsequent depletion of serotonin in synaptic cleft (Mol. Psychiatry 2003).

Schizophrenia is a complex mental disorder with a fairly high degree of heritability. Although the causes of schizophrenia remain unclear, it is now widely accepted that it is a neurodevelopmental disorder. Disrupted-in-schizophrenia 1 (DISC1) is a promising candidate susceptibility gene involved in neurodevelopment. To identify other susceptibility genes for schizophrenia, we screened for DISC1-interacting molecules in a Japanese population. We identified a 14-3-3epsilon gene region and schizophrenia (higher minor allele frequencies in controls). Both messenger RNA transcription and protein expression of 14-3-3epsilon were also increased in the lymphocytes of healthy control subjects harboring heterozygous and homozygous minor alleles compared with homozygous major allele subjects. 14-3-3epsilon (+/-) mice displayed defects in working memory and enhanced anxiety-like behavior. Our results suggest that 14-3-3epsilon gene is a possible schizophrenia susceptibility gene（Hum Mol Genet (in press)）.

Our mission in the Global COE is elucidation of pathogenesis and pathophysiology of mental disorders resulting from utilizing genomic medicine, cognitive neuroscience and molecular biology. Subsequently, we are going to realize 1) new preventive medicine and treatment, 2) new diagnostic system based on pathogenesis and pathophysiology, and 3) anti-stigma campaign through factual information about mental disorders.

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3. Ohnishi T et al. A Promoter Haplotype of the Inositol Monophosphatase 2 Gene (IMPA2) at 18p11.2 Confers a Possible Risk for Bipolar Disorder by Enhancing Transcription. Neuropsychopharmacology 32: 1727-1737 (2007)
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8. Hashimoto R et al. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Hum. Mol. Genet. 15: 3024-3033 (2006)
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