21st Century COE Program Human Nutritional Science on Stress Control
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Dr. Ohmori's Labo
Prof. Tetsuro Ohmori
Department of Psychiatry
Institute of Health Biosciences The University of Tokushima Graduate School, Tokushima, Japan Dr. Ohmori's Labo
Department of psychiatry is one of the clinical division of the COE program“Human Nutritional Science on Stress Control”. The Department consists of 20 psychiatrists, 5 psychologists and other stuffs. All members are involved in both clinical and research work. With collaboration with other department of the University, various studies are conducted on stress-related mental disorders. Its research methodology includes psychopathology, psychopharmacology, neuroimaging, molecular biology and molecular genetics.
Department of psychiatry has outpatient clinic and 45 beds inpatients ward. Psychiatrists and psychologists as well as other medical stuffs treat various psychiatric and psychosomatic diseases including mood disorders, anxiety disorders, stress-related disorders, obsessive compulsive disorders, eating disorders, schizophrenia, adolescent psychiatric disorders, developmental disorders and dementia. The department works as a psychiatric center of the Tokushima area with a population of 800,000. In addition, it also works as an educational and research center where young psychiatrists from all over Japan gather together to conduct clinical and basic research for the better understanding and treatment of mental disorders.
1. Clinical assessment and diagnosis
Current psychiatric diagnosis is made according to operational diagnostic criteria such as DSM-IV or ICD-10. Although reliable, their validity is uncertain. The department presided 27th annual meeting of Japanese society of psychiatric diagnosis, held Oct, 2007 in Tokushima and organized a symposium on the future direction of up coming DSM-V and ICD-11. A reliable and valid criterion is mandatory for both clinical and research purpose.
Our department has translated several psychiatric assessment scales such as Brief Assessment of Cognition of Schizophrenia, Subjective Quality of Life Scale for Schizophrenia and Calgary Depression Scale for Schizophrenia into Japanese, and contributed to the introduction of these scales into Japanese psychiatry. Dr.Y.Kaneda, who has studied in Vanderbilt Univ. from 2003-2005, is a leading investigator of this area. Using some of these scales, clinical evaluation has been conducted (eg.1,2).
2. Psychopharmacology and Psychopathology.
conferencePharmacotherapy of psychiatric disorders has been improved greatly since the introduction of newer antidepressants and antipsychotics. Effectiveness of new drugs have been studied extensively in depression, anxiety disorders and schizophrenia, and the results have been reported in international journals (eg.3,4). Department also participates in clinical trials of new drugs and the development of treatment algorism of depression and schizophrenia. Drs. T.Ohmori and K.Yamauchi lead this area.
Psychological aspect is an important area. Dr.M.Tomotake, who has studied in Univ. London from 2006-2007, translated a textbook and introduced a technique of analytical cognitive interview into Japan.
With the technique, patients with eating disorder are treated. Dr.Y.Izaki also studies psychopathology and psychotherapy in adolescent patients.
3. Neuroimaging.
Univ. Tokushima is one of a few hospitals where 3 thera MRI is available for ordinary patients. High magnetic field MR spectroscopy enables the measurement of glutamate and GABA, important amino acid neurotransmitters. In collaboration with Department of Radiology, studies are in progress on the brain levels of the two amino in the patient with mood disorders, anxiety disorders as well as schizophrenia. The measurement revealed that lithium, a therapeutic agent for manic-depressive illness, changes brain levels of glutamate in normal volunteers (5). Near Infra-Red Spectroscopy is also available in our department, that allows a convenient and non-invasive measurement of hemodynamic change in the cortical areas of the brain. It has been shown that cognitive tasks and emotional stress promptly activate brain activity in the frontal areas (6). This method is now applied for the monitoring of brain activity in stress-related conditions. Drs.S.Sumitani and S.Tayoshi are the principle investigators.
Infra-red spectroscopy
4. Molecular biology
A series of studies have been conducted with collaboration of Department of Stress Science to establish a new biological marker of depression by profiling mRNA expression from the leukocytes of the patients by using the stress sensitive DNA chip. It was found hundreds out of forty thousands genes differently expressed in the patients. Using dozens of most significantly changed genes, depression was successfully diagnosed with high sensitivity and specificity. DNA chip method has a great advantage over pervious biological markers in that it can utilize hundreds of parameters from a small amount of peripheral blood cells. Thus, a complicated and probably heterogeneous disease such as depression could be adequately recognized. This approach has opened a novel and promising horizon in the search of a biological marker of depression. Levels of mRNA of several genes were also measured by RT-PCR, and those of mRNA of serotonin transporter, LIM, histone deacetylase 5 , and cycic AMP response element-binding protein 1 were significantly changed in the patients, and normalized after treatment (eg. 7). These molecules are thought to play critical roles in the pathophysiology of depression. Drs. Ohmori, Ueno and Iga are the principle investigators of these molecular biological studies. From Oct.2007, Dr.Iga continues his study in Univ. Mississippi using post mortum brain samples.
Diagnostic maker of depression using peripheral mRNA expression
5. Molecular genetics
Mr. Song, Graduate student from ChinaA large body of clinical evidence suggests the presence of genetic factors in the etiology of mental disorders such as schizophrenia and bipolar disorders. The genetic factors seem to interact complicatedly with environmental factors for mental disorders to emerge clinically. Identification of responsible genes would help invaluably for the better understanding of these disorders. Our department has conducted molecular genetic studies in schizophrenia and depression and found some new associations between candidate genes and disorders. Moreover, utilizing carefully taken clinical record of patients, clinical features are taken into consideration in the analyses. Thus, it has been found that BDNF polymorphism is associated with the age of onset and severity of symptoms of schizophrenia that resist to ordinary antipsychotic therapy, and also associated with psychotic features and suicidal tendency of depression (eg.8,9). Recently, cognitive dysfunction has been evaluated and incorporated in the association studies.
References
  1. Kaneda Y, et al. Brief assessment of cognitive function in schizophrenia: validation of Japanese version. Psychiatry and Clinical Neurosience(2007 in press).
  2. Aki H, et al. 2006 Subjective and objective quality of life, levels of life skills, and their clinical determinants I outpatients of schizophrenia. Psychiatry Research 2007 (in press).
  3. Taniguchi T, et al. Effect of antipsychotic replacement with quetiapine on the symptoms and Quality of Life of schizophrenic patients with extrapyramidal symtoms. Human Psychopharmacology Clinical and Experimental. 21(7),439-45, 2006.
  4. Yamauchi K, et al . A case with social phobia with obsessive-compulsive symptoms improved by paroxetine in combination with risperidone. Gen Hosp Psychiatry 26,241-247, 2004.
  5. Sumitani S, et al. Activation of the Prefrontal Cortex during the Wisconsin Card Sorting Test as Measured by Multichannel Near-Infrared Spectroscopy. Neuropsychobiology 53,70-76,2006.
  6. Shibuya-Tayoshi S, et al. Lithium effects on brain glutamatergic and GABAergic systems of healthy volunteers as measured by proton magnetic resonance spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 22; [Epub ahead of print] PMID: 17913322
  7. Iga J, et al. Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry 13;31(3),628-32,2007.
  8. Numata S, et al. Interaction between catechol-O-methyltransferase (COMT) Val108/158Met and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in age at onset and clinical symptoms in schizophrenia. J Neural Transm. 114(2),255-9, 2007.
  9. Song H, et al. Association between PNPO and schizophrenia in the Japanese population. Schizophr Res. 2007 Sep 11; [Epub ahead of print] PMID: 17851041.

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