To meet the needs in translational research of neuropsychiatric disorders, animal models should focus on a specific factor of dysfunction and their validity should be discussed in a multi-layer structure from molecules to observational phenotypes. Cognitive inflexibility is one of schizophrenia - characteristic cognitive capacities and Wisconsin Card Sorting Test is frequently used to obtain corresponding scores of extra-dimensional (ED) set shifting. Even in cases of rodents, ED set shifting task based on three categories of queues has been established and approaches to understand cognitive inflexibility in schizophrenia, as a multi-layer structure model of ED set shifting, are now available. In the course of dementia, deficit of paired association learning (PAL) is observed at its early stage and progresses. This specific cognitive capacity can be investigated in both human and rodents by a common experimental paradigm as schema - dependent learning of a map. Understanding schema - dependent PAL in a multi - layer structure model would be valuable to propose novel treatment strategies for dementia.

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In this paper, we introduce our recent studies to evaluate cognitive and behavioral functions in animals. First, we analyzed relationships among phase-locked gamma oscillation, parvalbumin-positive neuron density, and a cognitive function (pre- pulse inhibition) in the same individual mice. The results suggest that phase-locked gamma oscillation could be used as a biomarker of autism/schizophrenia with deficits in parvalbumin - positive neurons. Second, we developed a computerized 3D video analysis system for animal behaviors. The system enables more objective and precise analyses of 3D locations of various body parts. Here we applied the 3D system to a novel object recognition test (NORT) in rats and behavioral analysis of monkey spontaneous behavior. We believe that such new approaches will contribute to progress of translational researches based on more objective data.

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Translational research applies findings from basic science to enhance human health and well - being. In a medical research context, it aims to translate findings in fundamental research into medical and nursing practice and meaningful health outcomes. Translational research implements a “bench-to-bedside” , from laboratory experiments through clinical trials to produce new drugs, devices, and treatment options for patients. As a relatively new research discipline, translational research incorporates aspects of both basic science and clinical research, requiring skills and resources that are not readily available in a basic laboratory or clinical setting. For this purpose, it is preferable to use the same methods or biomarkers in preclinical and clinical study. While to detect the human endophenotype of psychosis in the psychiatric disease - model animal is useful for the investigation to determine the cause of illness and drug discovery. Neuroimaging techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) are beneficial for both animal and clinical studies, and good method for translational study. In this column, I introduce some neuroimaging endophenotypes of psychosis thought to be common to human and animals.

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If patients understand their illness and treatment, because of understanding of therapeutic goal of medical staff, treatment becomes more effective and smooth. In treatment of major depressive disorder, it is necessary to build a positive therapeutic relationship first, and inform patients about the nature of depressive disorder and its treatment to encourage patients’ compliance. After the information about depressive disorder is given, it is important to provide convincing disease models for patients and cultivate a shared understanding of treatment. We have conduct a cohort study on pregnant and parturient women and confirm several findings. Specifically, as a result of the depressive state: 1. Negative recognition like a Harm Avoidance appears (disappears by treatment) , 2. Recognition of a nurtured experience changes (They recognize that their mothers were overprotective) , 3. Bonding to a child falls. In this review, we discuss how explain about depressive disorder based on our study outcomes.

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All researchers have to share products of their research with patients and family who are longing for research progress. For that purpose, trying to explain the research findings clearly in sufficient time seems critical. What is thought to be important are; 1) to explain the aim of the study sufficiently, 2) to make the position of the specific study clear in the whole research of the disease, 3) to use technical terms carefully, 4) to explain the clinical significance of the findings and how they could be helpful for patients and family, with trying to avoid a misunderstanding, 5) to listen carefully to responses by patients and family and to make the utmost effort to answer their questions. In general, family members of patients understand the research findings better than expected by researchers. Opinions from patients and family could have profound and enlightening significance even if they are somewhat biased. Sharing products of research with patients and family could be an invaluable opportunity for researchers.

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There is few opportunity to share the results of psychiatry research between researchers and patients and their family members in Japan. The priority of the findings and results of a research is not approved unless the findings is published on a Journal. This may induce political affairs concerning the publication of the research findings and results. Furthermore, the incorporation of public universities and research institutes have intensified complex and political affairs as a result of the demand for increase of research results since 2004. For example, a patent is applied before the publication of the research findings on a journal to protect new findings. However, the most basic problem is a researcher’s view that does not consider patients and their family members as research partners, but just subjects for research. To improve the present status, researcher should establish a view that consider patients and their family members as research partners. In addition, it is effective to found a protective system of researcher’s findings before the publication and to develop a center for collaboration between researchers and patients and their family members.

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Recently, the number of the researcher with medical school background (MD scientist) is rapidly decreasing in the field of basic medical research. The decrease of MD scientists might halt the proceeding of various translational researches and undermine the potential for international competition in the field of medical research. To overcome this issue, MD-PhD course and MD scientist training program were launched at The University of Tokyo in 2002 and 2008, respectively. So far these programs have been noticeably contributing to harvest research mind in medical school students. However, under the present practical training system for medical doctors, we need a new system to make the carrier change from MDs to MD scientists easier even after the practical training. In this article, I will introduce the MD scientist training program at The University of Tokyo and discuss the potential new system suitable for various MD carrier path.

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In the field of psychiatry, psychopathological and/or psychoanalytic studies (i.e. MIND studies) tend to be located in opposition to biological studies (i.e. BRAIN studies). Fortunately the author has been engaged in both MIND studies (especially psychoanalysis) and BRAIN studies (focusing on microglia, immune cells in the brain) at a university hospital for more than 10 years. In accordance with bilateral experience, he has come to consider that both the mind and the brain worlds must be located in a complementary relationship. For example, he has recently hypothesized unconscious drives including “life instincts” and “death drives” in the mind may be derived from microglial activation in the brain. To clarify such hypothesis, he is now trying to organize a translational research system (at his university) . He herein introduces the roadmap of his research especially aimed towards young psychiatrists with the hope that biology-based psychiatrists come to be interested in psychoanalysis and see the other side.

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With an advance of technology and an increase in sample size, many genetic variants have been identified as risk factors for mental disorders including schizophrenia, autism spectrum disorder, and bipolar disorder. These genetic findings reveal the following: 1) mental disorders show substantial genetic heterogeneity, 2) genetic variants are often associated with risk for multiple mental disorders, 3) importance of rare variants of recent origin, and 4) implications of somatic mutations of neurons in mental disorders. These genetic findings also influence clinical and basic research on mental disorders. In this article, we describe CNV-based future studies including genome cohort study, model animal study, and induced pluripotent stem cell study.

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Schizophrenia consists of various different symptoms. Although various treatments for schizophrenia have been developed, it is unclear how a particular treatment will affect a specific patient. We are analyzing differences in markers of carbonyl stress between healthy controls and schizophrenic patients to more accurately characterize the disease. We are currently consolidating data from metabolic studies, genome analyses, induced pluripotent stem cell models, animal models, and post-mortem brains to build a database of basic and clinical findings on schizophrenia. This database will allow us to characterize different subclasses of the disease, understand the molecular bases, elucidate the genetic and environmental factors, and develop specific treatment strategies for each subclass of schizophrenia. We believe that human resource in the different field contributes to the development of novel treatments for schizophrenia and improvements in the QOL of patients.

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