So - called Disease - modifying drugs for dementia, especially Alzheimer disease, have been developed vigorously in recent years. However their clinical trials have not been success yet. Therefore, as a drug therapy for Alzheimerʼs disease, symptomatic drugs, that is donepezil, galantamine, rivastigmine, and memantine, must be relied currently. In 2011, WFSBP announced the Guidelines for the Biological Treatment of Alzheimer ʻs disease and other dementias to show the guidelines for the use of symptomatic drugs. Donepezil , the first cholinesterase inhibitor, has a long half- life and a selectivity of the acetylcholine esterase. Galantamine has an allosteric effect on nicotinic receptors as well as a cholinesterase inhibitory activity. Rivastigmine is characterized by having not only an effect on acetylcholine esterase but an effect on. butyrylcholine esterase. Memantine is a glutamate NMDA receptor antagonist to suppress the neuropathy by glutamate. In the light of these features, it is necessary to use symptomatic drugs properly.

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To present the brain bio - signatures of typical and atypical development across infancy to adolescence using functional magnetic resonance imaging (fMRI) , a diffusion tensor imaging (DTI) and near infrared spectroscopy (NIRS) . 　Dr. Koyama talked about the short - term effect of auditory exposure on resting - state functional connectivity and its relevance to emerging behaviors in 6-month- old typically developing infants. Understanding experience- induced plasticity during early infancy offers a future platform for clinical research in studying the brain- environment interface from birth. 　Dr. Choiʼs DTI studies illustrated the impact of the emotional maltreatment such as parental verbal abuse and domestic violence on brain development in their young offspring. Work on trauma shows trauma type - specific sequelae on developing brain and its implication on development of psychopathology. Dr. Pavuluri showed macro - model of functional and structural brain bio - signatures of pediatric bipolar disorder using fMRI and DTI methods. This offered targets for brain - based personalized treatments in pediatric bipolar disorder. Studies on pediatric bipolar disorder unraveled six dynamic functional circuits in the domains of affect and cognition. Dr. Ishii-Takahashi demonstrated the long- term effects of methylphenidate on brain function of attention deficit hyperactivity disorder (ADHD) in school- aged children using the NIRS. NIRS study in ADHD showed that long administration of MPH might be change brain function in children with ADHD even in the drug free. 　In sum, these findings demonstrate how environment shapes brain function, and how illness trajectory involves deviation from normal course. The promise of plasticity and brain- based target discovery in very early stages of development offer promise for prevention and early intervention in the vulnerable pediatric population.

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In the symposium entitled “Regulation of presenilin/gamma-secretase function; towards intervention of Alzheimer disease in future” , four speakers presented new data about presenilin/gamma-secretase. Okochi and Tagami presented that toxic Aβ42 is directly cleaved into non-toxic toxic Aβ38 in living cells and analyzed the process in detail. Dr. Nishimura presented that gamma-secretase activity undergoes an age-related, non-genetic modulation through analysis of Aβ peptides in CSF of cynomolgus monkeys. Dr. Funamoto presented that gamma-secretase distinguishes the ectodomain length of substrates and that the ectodomain of C99 (the precursor of Aβ peptides) is a potent target for substrate-specific inhibition of both beta-and gamma-secretases. Dr. Tomita presented that gamma-Secretase activity is regulated by its subcellular localization, which might impact the enzymatic activity and synaptic function. Each speaker summarized their presentation below together with one figure. Okochi and Dr. Nishimura presided chair.

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This symposium was organized by the Max Planck Institute of Psychiatry (President: F. Holsboer) and the National Center of Neurology and Psychiatry (President: T. Higuchi) to present and discuss recent progress in research on biomarkers and therapeutic targets of depressive disorder. The first speaker, H. Kunugi, showed that dexamethasone/CRH test is a useful marker for subtyping depressive disorder and that two molecules (FKBP5 and ABCB1) play an important role in the HPA axis regulation and the pathogenesis of depressive disorder. The second speaker, M. Ising, presented compelling data on the role of FKBP5 and ABCB1 to predict response to antidepressants and demonstrated that gene expression in the peripheral blood and single nucleotide polymorphisms of these genes are useful biomarkers for personalized medicine in the treatment of depressive disorder. The third speaker, T. Numakawa, presented his cell biology research showing that long- term exposure to excessive glucocorticoid, the end product of the HPA axis, has a detrimental effect on brain- derived neurotrophic factor (BDNF) function in cultured cortical neurons. The last speaker, CW. Turck, presented a series of studies in mice using proteomics and metabolomics. His group found that molecules related to energy metabolism and oxidative stress were commonly altered in mice with high anxiety - like behavior and those mice treated with paroxetine. Overall, the symposium was very fruitful to provide recent knowledge on important progress and future directions of research on biomarkers and therapeutic targets of depressive disorder, which will facilitate the cooperative relationship between German and Japanese researchers.

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One of the hypothesis of pathophysiology of psychiatric disorder is that it is caused by reduced neuronal plasticity including synaptic formation and adult neurogenesis dysfunction. This symposium will provide a platform to bring together various experts in the field of brain cytokine/hormone, and epigenetic and imaging studies in alcohol - induced brain damage and affective disorders to give comprehensive idea for progress in this field and produce possible new therapeutic peripheral- derived markers for its pathophysiological understanding and diagnosis.

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The Symposium S094; Multidimensional approaches to the understanding of the biological basis of psychiatric disorders: Experiences from the Japanese - German HeKKSaGOn collaboration of universities was organized by Thomas Schulze, Professor of University of Heidelberg, which was based on the Japanese - German HeKKSaGOn collaboration of universities. HeKKSaGOn is the consortium composed of six university research institutions in Germany and Japan, named after Heidelberg - Kyoto - Karlsruhe - Sendai - Göttingen - Osaka - network: I have overviewed the background of the symposium proposal and contents of the four presentations in the symposium. In addition to discussions on the results of biological research of mental illness, we discussed how we should proceed the biological research of psychiatric disorders. Since DSM- 5 was just been released from APA , just before WFSBP Congress, I described my personal thoughts on the impact on DSM- 5 to biological research of psychiatric disorders by pointing out the fact DSM- 5 is not fully prepared for the aim of promoting biological research.

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Autism spectrum disorders (ASD) is a highly heritable and life - long neurodevelopmental disorder with a reported prevalence as high as 1/100 in the general population, affecting a large number of people worldwide. Deficits in social behavior and interactions constitute a core and most prevalent symptom of ASD. Thus currently untreatable this deficit affects approximate 1% of general populations. Although neither neural nor genetic backgrounds for pathophysiology of autistic social dysfunction have yet been uncovered, recently, an increasing number of studies have revealed neural and genetic correlates of human social cognition and behavior and their dysfunctions. To promote integration of researches from various related areas for further development, this symposia covered speakers who utilized genetic examinations and functional and structural neuroimaging in both clinical and non - clinical populations. In their studies, research modalities were occasionally applied as combinations of multi - modalities such as studies examining association between functional neuroimaging indices and polymorphisms in related genes. We discussed across modalities and provided the current model for neurogenetic understandings of autistic social deficits. Such understandings can further provide candidate molecules for pharmacotherapy of autistic core symptoms.

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This symposium was organized by Prof. N. Müller (Ludwig- Maximilians- University, Munich, German) and the author, T. A. Kato (Kyushu University, Fukuoka, Japan). Immunological abnormalities in the brain have recently been highlighted in neuropsychiatric disorders. Recent human PET studies and postmortem studies have shown that microglial activation exists in patients with psychiatric disorders such as schizophrenia, autism and depression. Microglia, one of the glial cells in the CNS, play important roles as immunological/inflammatory players, which release inflammatory cytokines and free radicals. Recent human data give us the novel dynamic understandings of psychiatric disorders beyond neurochemical understandings via neurotransmitters. In our symposium, Dr. J. Steiner (University of Magdeburg, Germany) showed the recent evidence of microglial activation in the brain of major depression from the postmortem studies. Dr. S. Kano (Johns Hopkins University, USA) presented the importance of the glial contribution to pathophysiology of schizophrenia via inflammatory signaling based on his studies with animal models and human subjects. Dr. S. Stefan (University Hospital Hamburg-Eppendorf, Germany) showed us the importance of the neuroinflammation under the pathology of depression and depressive states from his clinical studies focusing on multiple sclerosis. Finally, the author, Dr. Kato introduced the microglial possible contribution to psychological development and psychosocial activities by his recent research focusing on social decision - making with minocycline, a famous microglial inhibitor, to healthy volunteers. We believe that our symposium shed new light on the advanced understanding of brain - immune interaction in psychopathology with neuropsychiatric disorders and other mental health conditions including normal human development.

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Serotonergic as well as noradorenergic systems have been implicated in the pathogenesis of depression. Recently, dopaminergic system has also caught attention in the pathogenetic mechanism of depression. Homovanillic acid (HVA), 　3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) are major metabolites of dopamine, noradrenaline and serotonin, respectively. 　In the present study, we measured plasma levels of HVA, MHPG and 5-HIAA in 18 Japanese inpatients with depression at the time of admission to the Department of Neuropsychiatry, Fukushima Medical University Hospital, and after the treatment. 　We looked at the association between the metabolites changes with clinical improvement using the Hamilton rating Scale for Depression (HAMD) . There was a significant association between the plasma HVA levels at admission and changes in HAMD scores. On the other hand, no significant association was observed for plasma MHPG levels and plasma 5-HIAA levels. These results suggest that in the patients who are hospitalized because of poor response to antidepressants, regulation of dopaminergic system is effective for improvement. These results also suggest that antipsychotics augmentation strategy is effective for patients with depression who have high plasma HVA levels at the time of admission.

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