Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 16 (Heian)

Organizer / Chair: Akira SAWA (Johns Hopkins Medicine, USA), Co-chair: Suresh SUNDRAM (Monash University and Monash Health, Australia), Discussants: ‌Noboru HIROI (University of Texas Health Science Center at San Antonio, USA), Naren P RAO (National Institute of Mental Health and Neurosciences, India)

Technological advances and collaborative efforts in psychiatric genetics have provided robust insights in molecular landscape of psychiatric disorders. How to interpret and fruitfully utilize genetic information in psychiatry and neuropharmacology is now becoming an opportunity but also a major challenge. In this symposium, three speakers will address this key question in this field from complementary viewpoints. The first speaker Steve Hyman will discuss a path from genetics to translational neuroscience. The second speaker Akira Sawa will introduce a strategy that focuses on deep phenotyping of patients, including molecular and cellular study. Finally, the third speaker Jun Soo Kwon will address this question from neuroimaging perspectives. Together, we hope that the symposium may be able to provide an intellectual framework in psychiatry and neuropharmacology in the coming decade.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 1 (Main Hall)

Organizer / Chair: Eric YH CHEN (Department of Psychiatry, University of Hong Kong), Co-chair: Ichiro KUSUMI (Department of Psychiatry, Hokkaido University Graduate School of Medicine, Japan), Discussants: ‌Sung-Wan KIM (Department of Psychiatry, Chonnam National University, Korea), Masafumi MIZUNO (Department of Neuropsychiatry, Toho University School of Medicine, Japan)

Psychotic disorders (including schizophrenia and related disorders) involve complex brain dysfunctions affecting up to 3% of the population. They constitute one of the highest disease burdens globally and locally. The conditions inflict devastating consequences for youth and adults at the most productive years in their life. Relapse is a common problem in the treatment of patients with psychotic disorders. While maintenance treatment can help prevent relapse, the long-term use of antipsychotics carries substantial side effects. Empirical data are lacking on the long-term effects of medication discontinuation. The clinical decision to discontinue or continue medication in first-episode psychosis patients who have been free of positive symptoms for a period of time is therefore difficult. The first speaker will present long-term outcome data from a first episode psychosis cohort who were previously randomized into early maintenance treatment or discontinuation in Hong Kong. It was found that patients with early medication discontinuation is associated with poorer clinical outcome after 10 years. The second speaker will investigate an alternative approach to discontinuation, namely dose reduction in remitted psychosis. The speaker will discuss an observational study “Impact of guided antipsychotic dose reduction in patients with psychosis under remitted states: a randomized control trial and prospective follow-up study” which has been launched in Taiwan since 2017. The last speaker will present data from a survey towards clinicians’ views on medication discontinuation in remitted first episode psychosis in Singapore. The data show the ambiguity in clinicians about stopping medication in remitted patients with first episode psychosis due to a lack of clear guidelines, as well as patients’ desire to stop medication.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 6 (401+402)

Organizer / Chair: Wen-Sung LAI (Department of Psychology, National Taiwan University, Taiwan), Co-chair: Masanari ITOKAWA (Tokyo Metropolitan Institute of Medical Science, Japan), Discussants: ‌Atsushi KAMIYA (Johns Hopkins University School of Medicine, USA), Ming-Che KUO (National Taiwan University Cancer Center, Taiwan)

Schizophrenia is a costly and devastating mental disorder that affects up to 1% of the population worldwide. This debilitating brain disorder typically emerges in late adolescence and early adulthood which characterized by three main symptoms: positive symptoms (e.g., hallucinations, thought disorder, motor problems, delusions, symptoms associated with psychosis etc.), negative symptoms (e.g., flat affect, social withdrawal, apathy, self-neglect, anxiety, lack of motivation, and decrease in IQ etc.), and cognitive deficits. Generally speaking, positive symptoms of schizophrenia often respond well to antipsychotic drugs. Negative symptoms of schizophrenia can often linger or worsen over time, accompanied by impaired cognitive function, such as working memory and executive function. Currently available antipsychotics have been mainly focused on positive and mood-related symptoms targeting the dopamine and serotonin receptor systems. The negative symptoms and cognitive impairments of schizophrenia, which cause a deteriorated quality of life in patients and their families, have become an unmet medical need for antipsychotic drug development. In addition to the conventional view of dopamine involvement in schizophrenia (i.e., dopamine hypothesis of schizophrenia), other neurotransmitter systems (e.g., glutamatergic neurotransmission) and therapeutic targets have gradually gained more and more attentions in the investigation of pathophysiology and treatment of schizophrenia in the recent decades. In response to the urgent needs in schizophrenia, it is imperative to perform functional assays for drug screening and evaluation, especially in preclinical studies. Preclinical animal studies are highly valuable and indispensable to the understanding of the underlying pathophysiological mechanisms of schizophrenia and the elucidation of the drug effects. In this symposium, 4 distinguished speakers from Japan, USA, and Taiwan were invited, including Dr. Kiyofumi Yamada at Nagoya University Graduate School of Medicine, Dr. Yijuang Chern at Academia Sinica, Dr. Takashi Kitamura at University of Texas Southwestern Medical Center, and Dr. Wen-Sung Lai at National Taiwan University. We will report recent intriguing data and discuss new pharmaceutical agents for unmet medical needs in schizophrenia from preclinical animal models to clinical studies. Our findings will shed light on developing new pharmaceutical agents for unmet medical needs in schizophrenia and other neuropsychiatric disorders.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 11 (502)

Organizer / Chair: Tomohisa MORI (Department of Pharmacology, Hoshi University, Japan), Co-chair: Tadashi SAIGUSA (Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Japan), Discussants: ‌Makoto TANIGUCHI (Department of Neuroscience, Medical University of South Carolina, USA), Yuta OHGI (Otsuka Pharmaceutical Co., Ltd., Japan)

Psychostimulants, such as amphetamine, methamphetamine and cocaine, have been widely abused worldwide, and exhibit strong potential for relapse. Most seriously, psychostimulants show a very high percentage of re-use. On the other hand, President Trump announced that U.S.A. is facing opioid crisis as a national public health emergency, and this social issue is not the social problem limited in the U.S.A. any more. A large and growing body of evidence has demonstrated that mesolimbic dopaminergic neurons, which project from the ventral tegmental area to the nucleus accumbens, play a key role in the reinforcing/rewarding effects of abuse drugs in humans/animals. Drug-dependence involves many factors, especially biological changes or adaptative responses in the brain as well as peripheral systems including organs. Furthermore, social, familial and environmental factors should be acknowledged. Thus, the treatment of drug abuse is complex; treatment strategies should include psychobiological, social, and pharmacological considerations based on the patient's background. So far agonist therapies are somewhat effective for the treatment of drugs abuse, there are currently no medications available to be completely satisfied for the treatment of drug abuse per se. To reach the goal of our research in the medication for drug-dependence, we need to know "where are we and/or where should we go?” In this symposium, 4 speakers are going to talk their cutting edge views to review these questions.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 12 (503)

Organizer / Chair: Hiroki ISHIGURO (Department of Neuropsychiatry and Clinical Ethics, University of Yamanashi, Japan), Co-chair: ‌Taku YAMAGUCHI (Department of Pharmacotherapeutics and Neuropsychopharmacology, Faculty of Pharmaceutical Sciences, Nagasaki International University, Japan), Discussants: ‌Akitoyo HISHIMOTO (Department of Psychiatry, Kobe University Graduate School of Medicine, Japan), Hirokazu MIZOGUCHI (Department of Physiology and Anatomy, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Japan)

Advances in molecular biology techniques including genetic tools have provided new knowledge and deeper insights in understanding the biological roles of the endocannabinoid system in psychiatric disorders. The remarkable advances in genetics of endocannabinoid system (ECS) are unravelling the genetic bases in a number of neuropsychiatric disorders, including depression, schizophrenia, addiction, autism spectrum disorders and neurological conditions of neuro-immune disorders. The ECS consists of two major receptors (CB1Rs and CB2Rs), endocannabinoids (eCBs) and the synthesizing and degradation enzymes for eCBs. Although CB1Rs have been well characterized, the neuronal expression of CB2Rs and their role in neuropsychiatric have been subjects of long standing controversy and debate despite new knowledge and advances. The new molecular techniques and transgenic approaches are being used to explore and identify the involvement of the elements of ECS in models of CNS function and dysfunction underlying neuropsychiatric disorders. There is also increasing global awareness and interest in regulation of brain endocannabinoid system by elements of environmental stress and age. The recent study suggest that patients derived induced pluripotent stem cells (iPS cells) will be a one of the unique models for studying mental disorders. In this symposium, we provide data from our studies with a background on dysfunction of ECS genes in intermediate phenotypes of neuropsychiatric disorders, and the methods and approaches that were used to assess the neurobehavioral and molecular changes associated with the functions of specific neural networks. The age-dependent neural changes via ECS are analyzed in brains of animal models, human postmortern brains, and developmental stage of neural stem cells, neurons and glial cells from iPS cells. Furthermore, the mechanisms by which the neuro-immune crosstalk is likely to impact on risk factors contributing to neuropsychiatric disorders will be addressed. The selected speakers from Japan and USA will discuss the compelling evidence from their studies and current knowledge of CBR genetics and behavioral modifications – from mice to human subjects.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 13 (501)

Organizer / Chair: Atsushi SATO (Department of Pediatrics, The University of Tokyo Hospital, Japan), Co-chair: Nobumasa KATO (Medical Institute of Developmental Disabilities Research, Showa University, Japan), Discussant: ‌Shiro SUDA (Department of Psychiatry, Jichi Medical University, Japan)

Knowledge on molecular mechanism of autism has been rapidly expanding. Analysis of autism associated with specific genetic disorders reveals its mechanisms as well as mechanism-specific potential therapy such as mTOR inhibitors in tuberous sclerosis complex-associated autism. However, a recent increase in the prevalence of autism implicates the presence of non-genetic factors that cause autism. Epidemiological studies point out the tight link between maternal administration of valproic acid (VPA), one of the major drugs for epilepsy and migraine, and increase in the risk of autism and developmental delay in their children. Exposure to VPA in utero is replicated in rodents, and these models have been investigated to understand molecular changes relevant to autism. Epigenetic factors such as paternal aging are also considered as the background of increasing prevalence of autism. Research with rodents born to aged fathers finds the relationship between paternal aging and autism in their offspring. In this symposium, recent advance in autism research is presented by Asian researchers with relevance to genetic, non-genetic, and epigenetic factors, which will deepen our understanding of molecular mechanism of autism.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 14 (Palace Room A)

Organizer / Chair: Hisato MATSUNAGA (Department of Neuropsychiatry, Hyogo College of Medicine, Japan), Co-chair: Tomohiro NAKAO (Department of Neuropsychiatry, Graduate School of Medicasl Sciences, Kyushu University, Japan), Discussants: ‌Takashi NAKAMAE (Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan), Eiji SHIMIZU (Department of Cognitive Behavioral Physiology, Graduate School of Medicine, Chiba University, Japan)

Obsessive-compulsive disorder (OCD) is a relatively common and frequently debilitating neuropsychiatric disorder that affects approximately 2% of the general population. OCD is characterized by intrusive and unwanted obsessions and compulsions, and by a waxing and waning course of symptoms that rarely remit.
Standardized treatments for OCD, including drugs (e.g., selective serotonin reuptake inhibitors; (SSRIs)) and cognitive-behavioral therapy (CBT), are well established and used worldwide. However, the effectiveness of current OCD pharmacotherapy is limited. To optimize this type of therapy, cross-sectional or longitudinal evaluations of individuals with OCD are needed, which focus on comprehensive psychopathological features such as primary or secondary comorbid disorders (e.g., tic-related-OCD, major depression), antecedent traumatic events, and the brain mechanisms that mediate temporal transitions, according to the duration of untreated illness or the chronic course of OCD. These clinical factors should be taken into account in developing an adequate treatment regimen for OCD patients who show insufficient responses to the standardized pharmacotherapy for OCD.
DSM-5 categorizes OCD as an obsessive-compulsive and related disorder (OCRD), based on the concept of an obsessive-compulsive spectrum. Among OCRDs, hoarding disorder, which is frequently comorbid with OCD, has been characterized as a treatment refractory disorder; the neurobiological mechanism of the disorder still remains to be elucidated. Thus, comorbidity of hoarding disorder or hoarding symptoms may also be associated with treatment resistance in patients with OCD.
Therefore, it may be crucial to consider such cross-sectional heterogeneity of OCD or OCRDs to fully understand the biological mechanisms underlying these disorders, and to develop more effective treatment strategies (including novel treatment approaches such as adaptation to neuromodulation).
In our symposium, we will discuss tic-related and trauma-related OCD and hoarding disorder, focusing particularly on novel treatment strategies based on the advanced understanding of each condition’s neurobiological mechanisms. We will also discuss neuromodulation as a possible treatment option for treatment-refractory patients with OCD or OCRD.

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 15 (Palace Room B)

Organizer / Chair: Hiroyuki UCHIDA (Department of Neuropsychiatry, Keio University School of Medicine, Japan), Co-chair: Makoto HIGUCHI (Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, Japan), Discussants: ‌Yuan-Hwa CHOU (Taipei Veterans General Hospital, Taiwan), Mitsuyuki MATSUMOTO (Virtual Venture Unit, Psychiatry, Astellas Research Institute of America, San Diego, USA)

Advances in research of psychopharmacology have brought the hope for the treatment of psychiatric disorders. With the development of brain image techniques clinicians can learn more detailed information from the brain of psychiatric patients and devise more effective treatment strategies for them. The purpose of this symposium is to provide the state-of-art knowledge on treatment response, cognitions, and pathophysiology of the psychiatric illnesses that have been discovered with brain imaging. This symposium will provide the knowledge on, not only brain imaging itself, but also its application to clinical practice as well as research.
The first speaker will discuss predictors of antipsychotic responsiveness in first episode psychosis (FEP). It has been reported that dopaminergic activity in schizophrenia is related to responsiveness to antipsychotic drugs. For example, patients who respond well to first-line antipsychotic drugs show increased presynaptic dopamine synthesis, while treatment-refractory patients with schizophrenia exhibited a similar level of dopamine activity. The refractory schizophrenia is considered to be related with glutamatergic abnormality. Regarding antipsychotic responsiveness, different neurobiology may underlie schizophrenia between treatment responsive and treatment refractory patients. In this presentation, the speaker will review the evidence on presynaptic dopamine activity and glutamate level measured in drug-naïve FEP and their relationship with antipsychotic responsiveness.
The topic from second speaker will be “Neurobiology of cognitive deficits and treatment implications”. The evidence from several lines of research suggests the differential neurobiology for positive and cognitive symptoms of schizophrenia; while decreased dopamine release is considered to underlie the neurocognitive symptoms, neuropeptides play a critical role in the pathogenesis of social cognitive deficits typically seen in schizophrenia. This difference in neurobiology makes a strong case for rational use of add on interventions for the treatment of cognitive deficits in schizophrenia. Psychostimulants in the form of dopamine agonists and neuropeptides oxytocin - vasopressin are potential novel treatments for cognitive deficits in schizophrenia. This talk will focus on the neuroimaging studies examining the neurobiology of cognitive deficits and potential treatment for the same.
The third speaker will show the recent data on AMPA receptors (AMPAR) in multiple psychiatric illnesses. With the development of a new ligand, we can visualize AMPAR in the living human brain. The results from our pilot study have already revealed distinct patterns of AMPAR distributions in major psychiatric illnesses, including schizophrenia. Clinical relevance of these findings will also be discussed.
The last speaker will present “glutamatergic dysfunction in treatment-resistant schizophrenia: a 3T proton MRS study”. In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: (1) responsive to first-line antipsychotics (non treatment-resistant schizophrenia [nTRS]), (2) treatment-resistant to non-clozapine (CLZ) antipsychotics but CLZ-responsive (non-URS), and (3) treatment-resistant to both non-CLZ antipsychotics as well as CLZ (ultra treatment-resistant schizophrenia [URS]). The glutamatergic hypothesis may account for this classification. Thus, the aim of this presentation is to systematically review proton magnetic resonance spectroscopy (1H-MRS) studies to compare glutamatergic neurometabolite levels among these three patient groups and healthy controls (HCs).

Fri. Oct 11, 2019 8:40 AM - 10:20 AM Room 16 (Heian)

Organizer / Chair: Shinya KASAI (Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Japan), Co-chair: Shuji IRITANI (Department of Psychiatry, Graduate School of Medical Science, Nagoya University, Japan), Discussants: ‌Shigeki YAMAGUCHI (Department of Anesthesia and Pain Medicine, Dokkyo Medical University, Japan), Hiroki TANAKA (Department of Legal Medicine, Asahikawa Medical University, Japan)

Psychiatric disorders are largely multi-factorial conditions, and the identification of both genetic and environmental factors are important to better understand their pathophysiology and to develop improved treatment strategies. In particular, the impact of various environmental factors that influence the individual during early development, childhood, youth and adulthood, and their relative importance for the development and course of each specific psychiatric disorder is important to assess.
Animal experiments allow for studies of affected brain regions with many methods that cannot be applied on living human subjects. From such experiments, we can learn detailed pathophysiological pathways of disease, but it may be difficult to translate these findings to the clinical setting. In contrast to several somatic diseases, where biochemical tests can show the similarities with the corresponding human conditions, the animal models of psychiatric diseases such as depression suffer from gold standard markers of disease to prove the model´s resemblance of the same condition in humans.
Non-invasive visualization approaches with e.g. magnetic resonance imaging techniques have contributed substantially to our understanding on the pathology of many psychiatric diseases, but these studies cannot provide cellular or molecular pathologies in the brain.
Postmortem human brain studies have been conducted for more than a century to elucidate the underlying pathologies of various psychiatric and neurologic diseases, but these have been dominated by studies of structural changes. In recent years, methodological improvements have allowed for the application of a variety of analyses of postmortem brain tissue, and today reliable information from genomics, transcriptomics and proteomics can be obtained and used to characterize specific psychiatric conditions. However, for postmortem human studies it is crucial that the regions studied are precisely neuroanatomically identified, that the postmortem condition of the tissue is good, and that the phenotyping is accurate and comprehensive.
At this symposium, four researchers present studies on postmortem human brain with different purposes and approaches. The attendee will learn the possibilities that such studies can offer, but also explain important pitfalls and shortcomings, and how to avoid these.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 1 (Main Hall)

Organizer / Chair: Roumen MILEV (Department of Psychiatry, Queen's University, Canada), Co-chair: Tadafumi KATO (Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Center for Brain Science, Japan), Discussant: ‌Carlos A ZARATE (NIH / NIMH, USA)

Background: Mood disorders are highly prevalent, associated with significant personal and societal burden. Depression is one of the leading causes of disability world-wide. Bipolar Disorders are associated with high levels of recurrence and pose treatment challenges. Although there are numerous treatment modalities and compounds available, the outcome results are underwhelming. There are no biological tests or markers to predict therapeutic response to a treatment, we don’t know how to predict severity of depression or our next treatment step. We don’t have a good understanding of how to effectively implement evidence-based treatment guidelines, how to change physician prescribing behaviour, or how to use mobile health technology to inform our choices. There is an exponential growth in research endeavours, but their translation to clinical practice, and patient outcomes is severely lacking. This symposium sets a high standard of goals and objectives. Several primers of successful translation of research findings into clinical practice in mood disorders will be presented. Development of evidence-based and clinical practice informed treatment guidelines for management of patients with mood disorders is an example of improving our approach to treatments, but their implementation has not been satisfactory. In this symposium we will present how a point of care app can shift physician prescribing behaviour to become aligned with the guidelines. We will explore the use of mobile health technologies in the clinical decision making and influencing the treatment outcomes. A focus on utilization of machine learning paradigms will exemplify predicting depression severity. Preliminary results of predictors of treatment response in major depressive disorders, as discovered by the large Canadian Biomarkers Integrated Network in depression (CAN-BIND) series of studies will be presented as well. We will have ample opportunities for discussion and commentaries.

Learning Objectives: After attending this symposium the participant will be able:

1. To review CANMAT/ISBD treatment recommendations for management of bipolar disorder
2. To demonstrate the feasibility of using a point of care APP to change physician prescribing behaviour
3. ‌To understand the various approaches to quantify psychiatric disorder severity utilizing information communication technologies.
4. To discuss the difficulty and potential benefit/risk of utilizing machine learning in the psychiatry field.
5. ‌To understand the goals and results of the large CAN-BIND project and the importance of identification of biomarkers for treatment response
6. To understand the concept of digital phenotyping applied to mental health research.
7. ‌To explore the use of mobile health technologies (M-Health) for patient engagement, measurement-based care and monitoring of wellness or relapse in mood disorders

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 6 (401+402)

Organizer / Chair: Mitsuhiro YOSHIOKA (Department of Neuropharmacology, Hokkadio University Faculty of Medicine, Japan), Co-chair: Masaki KAKEYAMA (Lab. Environmental Brain Science, Faculty of Human Sciences, Waseda University, Japan), Discussants: ‌Takeshi INOUE (Department of Psychiatry, Tokyo Medical University, Japan), Koji YANO (SHIONOGI & CO., LTD., Japan)

Selective serotonin reuptake inhibitors (SSRIs) ameliorates depressive symptoms in humans. However, the therapeutic effects are limited due to the delayed effects and side effects. There are two origins of serotonergic projections to the forebrain, the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN), and each nucleus projects to different brain regions, with some overlapping. Moreover, seven families of serotonin 5-HT receptors comprising a total of 14 subtypes have been identified, and each subtype has distinct functions. Given the complexity of serotonergic system, to dissect the system might make it possible to avoid side effects and to exert rapid effects. In this symposium, Yu Ohmura will show the data indicating that distinct serotonergic pathways and specific type of 5-HT receptor regulate anxiety, impulse control, and depression. Emily Jutkiewicz will introduce the idea that a specific downstream mechanism of 5-HT1A receptors is essential to exert antidepressant-like effects. Makoto Kondo will provide an insight into the antidepressant-like effects induced by the activation of a 5-HT3 receptor-IGF1 mechanism. Takeshi Inoue will criticize these findings from the view of psychiatrists and suggest the direction of future research.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 7 (403)

Organizer / Chair: ‌Mong-Liang LU (Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taiwan), Co-chair: Takashi WATANABE (Department of Psychiatry, Dokkyo Medical University School of Medicine, Japan), Discussants: ‌Catherine WEISS (Otsuka Pharmaceutical Development & Commercialization Inc, USA), Michiko FUJIMOTO (Department of Psychiatry, Osaka University Graduate School of Medicine, Japan)

The metabolic syndrome is highly prevalent in patients with schizophrenia patients and represents an enormous source of cardiovascular risk and mortality. Appetite-regulating hormones, pharmacodynamics and alterations in glucose metabolism may underlie the negative effect of antipsychotic medications. In this symposium, we provide the multidimensional approach to metabolic disturbance in schizophrenia from the aspects of epidemiology, therapeutic drug monitoring, and potential biomarkers.
Prof. Lu ML: Acyl/Desacyl ghrelin ratio as a potential biomarker for metabolic syndrome in patients with schizophrenia
Circulating ghrelin is presented in two major forms, acyl ghrelin and desacyl ghrelin. Both ghrelin forms can mediate energy metabolism and may act antagonistically. This suggests a crucial role for the acyl/desacyl ghrelin ratio in the energy homeostasis. In this study, we found that acyl/desacyl ghrelin ratio was more strongly correlated with metabolic syndrome components than total ghrelin and desacyl ghrelin with them. And acyl/desacyl ghrelin ratio had a higher discriminative ability to differentiate patients with metabolic syndrome from those without metabolic syndrome than either total ghrelin or desacyl ghrelin. Our study results suggest that acyl/desacyl ghrelin ratio may be a preferential marker of metabolic syndrome in patients with schizophrenia
Prof. Wu TH: Therapeutic Drug Monitoring of olanzapine and its desmethylaed metabolite in schizophrenic patients
Therapeutic drug monitoring of olanzapine (OLZ) and its desmethylated metabolite (DMO) were applied to identify the roles of the olanzapine methylation metabolite in metabolic and efficacy regulation of schizophrenic patients. In summary, our studies revealed that COLZ≧22.77ng/mL was a positive predictor of therapeutic efficacy in patients with schizophrenia and it was proposed that the optimal OLZ treatment should maintain concentrations ratio of OLZ/DMO between 3 and 6 to maximize the clinical efficacy and minimize the metabolic side effects.
Dr. Chen BY: Orexin-A may plays the role in regulating metabolic status in patient with schizophrenia taking antipsychotics
Orexin-A promotes thermogenesis and energy expenditure via increasing sympathetic tone and this effect is supressed by antipsychotics treatment. We found that orexin-A is up-regulated in antipsychotics-treated patients with schizophrenia, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels are associated with better metabolic outcomes. These observations suggest orexin-A may have a protective effect against the development of metabolic abnormalities in schizophrenia patients receiving long-term antipsychotic treatment.
Dr. Sugai T: Characteristics of physical risk in Japanese patients with schizophrenia
We investigated the risk of metabolic syndrome and underweight by questionnaire, and there were 7655 outpatients and 15461 inpatients with schizophrenia. The result revealed that metabolic syndrome prevalence in Japanese outpatients was approximately 3-fold higher than in inpatients. On the other hand, the prevalence of underweight and under-nutrition in Japanese inpatients with schizophrenia was higher than in outpatients and the general population. The results also suggest that the difference in physical health between outpatients and inpatients with schizophrenia may be related to the mental health system in Japan. We should pay more attention to the risk of physical disease in Japanese patients with schizophrenia, considering the difference in health characteristics between outpatients and inpatients in clinical practice.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 11 (502)

Organizer / Chair: Chieko KURIHARA (National Institute for Quantum and Radiological Science and Technology, Japan), Co-chair: Kazutaka SHIMODA (Department of Psychiatry, Dokkyo Medical University, Japan), Discussants: ‌Lillian COMAS-DÍAZ (The George Washington University School of Medicine, USA), Frederick M JACOBSEN (The George Washington University School of Medicine, USA)

Mental, neurological and substance use disorders have been revealed to contribute to the Global Burden of Disease. To overcome this situation and to achieve cost-effective community care improvement respecting for human rights in various cultural contexts, evidence-based interventions including psychiatric pharmacotherapy along with community engagement and capacity development are prerequisite. Especially in recent years, in the era of global drug development and world-wide big data analysis, both of medical professionals and patients are drastically moving around the world. This has been caused by rapid development of information technology facilitating global communications, as well as the growth of easy and inexpensive transportation means. Some are seeking for better working places or better healthcare services; others are evacuating from conflict area or traveling for disaster relief. Considering such situations, we have to seek for evolutional change of drug development strategies, along with model change of community care, with enlightening perspective of psychiatric pharmacotherapy to achieve Global Mental Health.
In this symposium, speakers from Asian countries will introduce their experience in their activities to facilitate community care, including innovative psychiatric pharmacotherapy strategies, towards the achievement of Global Mental Health:
Chieko Kurihara, Senior Researcher, National Institute for Quantum and Radiological Sciences and Technology will present opening remarks of this symposium and provide a view of community care, along with global drug development and psychiatric pharmacotherapy strategies towards Global Mental Health.
Tae-Yeon Hwang, Director of Mental Health Services and Planning, National Center for Mental Health, South Korea, will introduce his activities in newly-built National Center, in their new era of revised Mental Health Act, as well as his international activities in collaborative partnership with Asian psychiatrists for facilitating community care, clinical research as well as improvement of psychiatric pharmacotherapy in each country.
Tiur Sihombing, Duren Sawit Narcotic and Mental Hospital, Indonesia, will introduce her hospital organization to provide mental health service collaborating with extensive specialists of comorbidities, such as internists, pediatricians, gynecologists, etc.(consultation liason psychiatry). Also she will introduce their engagement in rational drug use, according to guidelines, as well as community empowerment in low resource settings.
Yang Yen-Kuang, Professor of the Department of Psychiatry, National Cheng Kung University will introduce his long-standing contribution to mental health in Tainan city sometimes collaborating with local government as well as facilitating clinical trial for implementing new medications. He will show some key strategies for successful evidence-based community care, along with innovative drug development and translational research, based on his expertise and experience.
Kazutaka Shimoda, Professor, Chairman of the Department of Psychiatry, Dokkyo Medical University, will present overviewing summary of this session and closing remarks.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 12 (503)

Organizer / Chair: ‌Yasue HORIUCHI (Department of Psychiatry and Behavioral Sciences,Tokyo Metropolitan Institute of Medical Science, Japan), Co-chair: Hiroshi YONEDA (Department of Neuropsychiatry, Division of Comprehensive Medicine, Osaka Medical College, Japan), Discussants: ‌Akira SAWA (Johns Hopkins University School of Medicine and Bloomberg School of Public Health, USA), Daisuke NISHIZAWA (Tokyo Metropolitan Institute of Medical Science, Japan)

Schizophrenia is a highly inheritable disorder, human genetics and genomics is a natural and powerful tool to study this disorder. Large-scale genetics studies have identified hundreds of loci underlying schizophrenia and provided initial insights into their disease pathogenesis. However, most of these studies were restricted to samples of European ancestry, limiting both scientific knowledge and its application from most of the world’s population. To address this important gap in scientific knowledge while advancing global mental health equity, the Stanley Center has launched a global initiative to increase sample sizes for psychiatric research within diverse populations across the world.
Our efforts in mapping the genetic variants that drive risk in the population have taken a more global view, with the coordination and completion of the pan-Asian genome-wide association study of schizophrenia.
In our first study, Asians showed highly consistent effect sizes to those in Europeans, suggesting that the genetic basis of schizophrenia and by extension its biology is broadly shared across major world populations. Integrating the pan-Asian results with the European schizophrenia meta-analysis identifies almost 90 new schizophrenia genetic loci.
These initial investigations into the genetics of schizophrenia in Asia have demonstrated the value of a global perspective on genetic risk. To fully capture genetic risk for schizophrenia and other psychiatric diseases, we have launched the SC Global Collection Initiative, which aims to collect ~100,000 samples over the next four years. These efforts focus on diverse populations, including multiple collection efforts in Ethiopia, Kenya, South Africa, Uganda Mexico, China, Japan, Australia, and Finland.
In this symposium, we will discuss the current status of our project from China, USA and Japan.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 13 (501)

Organizer / Chair: Kazuyuki NAKAGOME (National Center of Neurology and Psychiatry, Japan), Co-chair: Akira MONJI (Department of Psychiatry, Saga University Faculty of Medicine, Japan), Discussants: ‌Mitsuhiko YAMADA (Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan), Shinji TAKAHASHI (Taisho Pharmaceutical Co., Ltd., Japan)

Schizophrenia is a fairly common and devastating mental illness characterized by positive and negative symptoms, with cognitive dysfunction. Patients with schizophrenia are usually treated with antipsychotic medication. However, 10-30% of schizophrenic patients are treatment resistant, and the pharmaceutical industry still considers schizophrenia as an attractive target for drug design and there are many novel agents in early development. Recently, some abnormalities in neural circuits and brain networks are proposed as objective biomarkers for positive symptoms, such as hallucinations or delusions. These biomarkers could be used in different stages of clinical drug development (mechanism of action, target engagement, use as diagnostic test, enrichment of study populations, stratification for subgroups, safety and efficacy markers, etc.). In addition, these abnormalities can also be studied in animal models to facilitate the discovery of new targets and drug candidates. The purpose of this symposium is to discuss the novel strategy to treat hallucinations and delusions in schizophrenia, based on the findings obtained from translational researches using advanced techniques to study neural circuits and brain networks. Potential use of the biomarkers in drug development would also be discussed. The first speaker will review the recent advancement of connectivity studies of hallucinations and delusions in schizophrenia. The topic includes salience-associated networks underlying psychosis and structural and functional connectivity associated with abnormal conservatism bias and the jumping to conclusions bias in patients. It is reported that 60-90% of patients with schizophrenia suffer from auditory hallucinations. It is hypothesized that auditory-verbal hallucinations are caused by an inner-speech abnormality. The second speaker will introduce the project exploring the causes of auditory-verbal hallucinations with a novel electrophysiological marker of inner-speech. On the other hand, patients with schizophrenia have been hypothesized to have a functional impairment in filtering irrelevant sensory information, which may result in hallucinations and delusions. The third speaker will review possible association between the auditory gating deficits and positive symptoms, focusing on the abnormalities in spontaneous gamma activity in schizophrenia. Finally, the fourth speaker will review the abnormal thalamocortical networks in schizophrenia. The topic includes the translational research using a novel mouse model to study roles of parvalbumin-expressing GABAergic neurons in the pathophysiology of schizophrenia. We hope that this symposium will help the audience to understand the recent advancements of translational researches focusing on abnormalities in neural circuits and brain networks to treat hallucinations and delusions in schizophrenia.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 14 (Palace Room A)

Organizer / Chair: Tung-Ping T SU (Department of Psychiatry, Cheng-Hsin General Hospital, Taipei, National Yang-Ming University, Taiwan), Co-chair: ‌Hisashi MORI (Department of Molecular Neurosciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan), Discussant: ‌Nagahide TAKAHASHI (Hamamatsu University School of Medicine, Japan)

The N-methyl-D-aspartate (NMDA) receptor antagonist ketamine exerts rapid and sustained antidepressant effects in depressed patients. Ketamine is a racemic mixture of equal amounts of enantiomers, (R)-ketamine and (S)-ketamine. The neural mechanisms that underlie different effects of these enantiomers remain unclear. Recent animal studies has demonstrated that (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)-ketamine. However, neural mechanisms that underlie different effects of these enantiomers still remain unclear. Further, GluN2D is a subunit of NMDA receptor, which plays an important role for the fast antidepressant effect of ketamine. The first study, presented by Dr. Ide to investigate the rapid and sustained antidepressant cognitive impairment effects of these enantiomers on the mice with and without GluN2D (wildtype) using TST and Novl Object Recognition Test (NORT) respectively. The second speaker Ago using chronic corticosterone –induced (CORT) mouse model depression confirms that (R)-ketamine exerts higher potency in antidepressant effects than (S)-ketamine, also do the metabolites (2R, 6R, Hydrooxynorketamine). He has tried to use the technique of microdialysis to analyze the concentration of neurotransmitters related to the different enantiomers in order to clarify the common and distinct neural mechanisms for antidepressant effects of ketamine and its enantiomers. Up to date, there has no clinical trial of (R)-ketamine in humans, the third speaker Chen conducted a double-blind, randomized ketamine vs. placebo study and tried to understand how the changes of brain connectivity using FcMRI technique to support the PFC-related circuit modulation associated with the rapid antidepressant effects of ketamine. The final speaker Su initiated a maintenance therapy for ketamine responder by a double blind, RCS, with D-cycloserine vs. placebo for 7 week study to see if the partial agonist of glycine site on NMDA receptor could continue to sustain the response of ketamine on treatment resistant depression.

Fri. Oct 11, 2019 10:30 AM - 12:10 PM Room 16 (Heian)

Organizer / Chair: ‌Atsumi NITTA (Dept of Pharmaceutical Thera & Neuropharmacol, Fac of Pharmaceutical Sci. Grad Sch of Med and Pharm Sci.University of Toyama, Toyama, Japan), Co-chair: Hiroshi ICHINOSE (School of Life Science and Technology, Tokyo Institute of Technology, Japan), Discussants: ‌Kazuto KOBAYASHI (Department of Molecular Genetics, Fukushima Medical University, Japan), Kiyoyuki KITAICHI (Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Japan)

We are always receiving many and various stresses. Stresses sometime induce depressive disorder and anxiety, fall to drug addiction. Many patients are not received efficient therapy, since mechanism of onset of depressive disorders anxiety is not completely clarified, especially induced by stresses. Further many factors could be involved for the onset depressive disorders and/or anxiety, cocaine or methamphetamine, abuse, neglect, gene, environment, trauma, gender and etc. However we do not perfect medical tools for the depression and/or anxiety.
Here, we will focus to gender differences in the depression, GluK3-containing kainate, genomic factor of Shati/Nat8L.
We would like to discuss the mechanism of depression and anxiety, in order to novel medical tools in near future.

Fri. Oct 11, 2019 4:30 PM - 6:10 PM Room 6 (401+402)

Organizer / Chair: Chun-Hsin CHEN (Department of Psychiatry, Municipal Wan-Fang Hospital, Taipei Medical University, Taiwan), Co-chair: Katsuji NISHIMURA (Department of Psychiatry, Tokyo Women's Medical University, Japan), Discussant: ‌Hiroaki TOMITA (Department of Psychiatry, Graduate School of Medicine, Tohoku University, Japan)

Background: Accumulating evidence indicates that the gut microbiota can communicate with central nerve system, and thereby influences brain function and behavior, including mood symptoms. Preclinical studies have shown that consumption of probiotics may alter brain functions and reduce anxiety- or depression-like behaviors. Objective: The symposium aims to demonstrate some evidence of relationships between mood symptoms and microbiota, which may be significantly affected by diet or probiotics, in diverse subjects. First, Dr Okubo will report the association of fear of cancer recurrence (FCR) with omega-3 PUFAs and gut microbiota among breast cancer survivors. FCR among breast cancer survivors especially with chemotherapy history could be controlled by prudent dietary modification considering PUFAs and gut microbiota. Nutritional intervention considering PUFAs and probiotics to alleviate FCR will be proposed in the symposium. Second, Dr Kuo will report the comparisons of consumption of nitrated cured meat and composition of microbiota between patients with mood disorder and healthy control. In addition, peripheral gene expression patterns in patients with bipolar disorder during acute versus remission status will be evaluated. Finally, potential relationships between microbiota targets, nitrated meat consumption, and gene expression in human samples will be explored. Third, Dr Chen will review consumptions of probiotic to alleviate depressive symptoms in different kinds of participants and report meta-analysis of these human studies. Finally, a pilot study augmenting Lactobacillus plantarum PS128 in patients with major depressive disorder and stabilized antidepressant treatment will be reported.

Fri. Oct 11, 2019 4:30 PM - 6:10 PM Room 7 (403)

Organizer / Chair: Soichiro IDE (Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Japan), Co-chair: Ichiro SORA (Department of Psychiatry, Kobe University Graduate School of Medicine, Japan), Discussant: ‌Masahiro SHIBASAKI (Department of Pharmacology, Hoshi University, Japan)

Recently, various addiction problems have spread in Asian countries, and the situation is growing serious. Addiction is a condition that results when individuals ingest an addictive substance or perform a specific action that can be pleasurable but the continuous use or act of which becomes compulsive and interferes with ordinary life responsibilities. It is very important to clarify the mechanisms underlying addiction, but there are still many unclear points. Animal studies have been crucial in understanding the biology and pathophysiology of drug addiction. In this symposium, we would like to introduce the latest knowledge about addiction by the researchers who are working on elucidating the mechanisms of addiction by animal studies. We hope that not only those who are directly involved in the clinical situation, but also basic researchers who are interested in research about decision making, function and pathology of reward systems, and behavioral pharmacology will widely participate in the symposium and discuss perspectives in animal models of addiction.

Fri. Oct 11, 2019 4:30 PM - 6:10 PM Room 12 (503)

Organizer / Chair: Andi Jayalangkara TANRA (Department of Psychiatry, Faculty of Medicine, Universitas Hasanuddin, Makassar, Indonesia), Co-chair: Minoru TAKEBAYASHI (Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, Japan), Discussant: ‌Kristian LIAURY (Department of Psychiatry, Hasanuddin University, Indonesia)

Currently, there is an increasing number of techniques developed for biomarker of mental disorders.
One of that is the sAA (Salivary Alpha Amylase) Enzyme, which is produced by parotic gland in oral cavity. This enzyme could predict the level of stress from patients such as Psychotic, Depression, Bipolar and Anxiety through SAM (Sympathetic Adreno Medullary) system. Measuring the level of this enzyme is easy, safe and non-invasive, nonetheless the result is still in controversy.
However, the trait marker represents the properties of biological processeson behavior which play antecedent and possiblythe pathophysiology role of mental disorder such as schizophrenia.
Therefore, serotonin transporter (SERT) system is still challenging to be explored as a biological marker of major depression, focused in animal model. Dysregulation of immune system is also closely involved in the pathogenesis of depression.
Finally, the glutamate decarboxylase like protein 1 (GADL1)variant could be used as a biomarker to predict therapeutic response to lithium maintenance treatment in bipolar l patients.
The 4 speakers will give contribution for elaborating future development of Biomarker for mental disorders and will enhance interesting discussion in our symposium.

Fri. Oct 11, 2019 4:30 PM - 6:10 PM Room 13 (501)

Organizer / Chair: ‌Ryota HASHIMOTO (Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Japan), Co-chair: ‌Michio SUZUKI (Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Japan), Discussants: ‌Tetsuya MATSUDA (Tamagawa University, Brain Science Institute, Japan), Masaki FUKUNAGA (Division of Cerebral Integraton, National Institute for Physiological Sciences, Japan)

The ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium is an international effort by leaders worldwide. The Network brings together researchers in imaging genomics, neurology and psychiatry, to understand brain structure and function, based on MRI, DTI, fMRI, genetic data and many patient populations. The ENIGMA Network has several goals: to create a network of like-minded individuals, interested in pushing forward the field of imaging genetics, to ensure promising findings are replicated via member collaborations, in order to satisfy the mandates of most journals, to share ideas, algorithms, data, and information on promising findings or methods, to facilitate training, including workshops and conferences on key methods and emerging directions in imaging genetics. ENIGMA consists of over 30 active working groups (WGs). WGs are organized into four major research cores, sixteen Disease Working groups, six Genomics Groups, four Algorithm Development Groups three Healthy Variation Groups and three Collaborations with Other Consortia. ENIGMA published fifty three papers including review articles and Editorial.
COCORO (Cognitive Genetics Collaborative Research Organization), is the largest collaborative effort in biological psychiatry in Japan. The purpose of COCORO is to elucidate mechanisms of psychiatric disorders and brain function. Researchers in various fields such as neuroscience, molecular biology, genome science, psychiatry, neuroimaging, cognitive science, neurophysiology, psychology, neuropsychopharmacology, gather and exchange pioneer and promote new research fields. The interaction between clinical and basic researchers also facilitate understanding and exchange for translation. COCORO consists of over 30 institutes in Japan and running several projects including neuroimaging, neurophysiology, neurocognition and genetics. COCORO participated more than ten projects of ENIGMA, and also COCORO independently replicated the results of ENIGMA in several projects.
In this symposium, the representative of ENIGMA, Prof. Paul Thompson introduce the outline of ENIGMA. Then, achievement of Disease Working Group in Psychiatric Disorders and Algorithm Development Groups in Diffusion Tensor Imaging will be presented. Lastly, the achievement of COCORO will be presented in conjunction with successful replication of ENIGMA studies and new results. Future collaboration between ENIGMA and COCORO for replication and harmonization each other will be discussed.

Sat. Oct 12, 2019 8:40 AM - 10:20 AM Room 6 (401+402)

Organizer / Chair: Toshitaka NABESHIMA (Graduate School of Health Science, Fujita Health University, Japan), Co-chair: Yukihiro OHNO (Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan), Discussants: ‌Wen-Sung LAI (Department of Psychology, National Taiwan University, Taiwan), Ming-Huan CHAN (Institute of Neuroscience, National Chengchi University, Taiwan)

Schizophrenia, bipolar disorder and major depressive disorder are major neuropsychiatric disorders in world-wide. The patients with neuropsychiatric disorders should continuously take drugs to control their mental condition. Because many of the currently used neuropsychiatric drugs are symptomatic treatments that suppress the receptors and transporters. There are also severely ill patients who show poor or partial response to the drugs even if they receive appropriate medication. The key to preventing and curing neuropsychiatric disorders is to elucidate the mechanisms at molecular level. In this symposium, we will invite four speakers from Korea and Japan, and discuss about translational research for new drug development in neuropsychiatric disorders.
Professor Kim is neuropsychopharmacologist and toxicologist. He found that indoleamine 2,3-dioxygenase 1 (IDO1) gene play a crucial role in the neuropsychotoixc conditions. IDO1 is the first and rate-limiting enzyme in the L-kynurenine pathway and is induced by several pro-inflammatory cytokines, including IFNs, tumor necrosis factor, and interleukin 6. He will discuss novel drug target for bipolar disorder and serotonin syndrome.
Dr. Nagai is neuropsychopharmacologist in schizophrenia research field. His collaborators recently identified novel copy-number variation (CNV) of several gene associated with the disease, including ARHGAP10, a member of the RhoGAP superfamily. They also generated a mouse model of a patient with a CNV in the ARHGAP10 gene. He will provide exciting results regarding novel animal model of schizophrenia developed from reverse translational research.
Dr. Kunisawa is one of the excellent young investigators in the research field of major depressive disorder. The metabolism of L-tryptophan (TRP), an essential amino acid, in extrahepatic tissues proceeds through the L-kynurenine (KYN) and the serotonin (5-HT) pathways. His research group found that TRP metabolism plays a critical role in depression induced by IFN-α and physical stressor.
Professor Noda is a neuropsychopharmacologist in the basic fields of psychiatric disorders (neurodevelopmental disorders, schizophrenia, stress-related disorders etc). Abnormalities of glutamate transporters (GLTs) cause some neurodevelopmental disorders, such as ADHD and schizophrenia. He found that functional roles of glial GLT in neurodevelopment under the physiological and pathological conditions using the mice with varying expression of transporter. His model may provide one useful tool for elucidating the contribution of glutamate dysfunction to the pathophysiology of psychiatric disorders, and glial GLT will be a new target molecule for their therapeutics.
These findings suggest that IDO, ARHGAP10, TRP and GLT are novel target for the treatment of neuropsychiatric disorders.

Sat. Oct 12, 2019 8:40 AM - 10:20 AM Room 11 (502)

Organizer / Chair: ‌Tetsuro OHMORI (Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Japan), Co-chair: Yasunori MORIO (Translational Medical Center, National Center of Neurology and Psychiatry, Japan), Discussants: ‌Kotaro HATTORI (Medical Genome Center, National Center of Neurology and Psychiatry, Japan), Tetsurou KIKUCHI (New Drug Research Division, Pharmaceutical Business Division, Otsuka Pharmaceutical Co., Ltd., Japan)

Schizophrenia is a complex psychiatric disorder with a lifetime morbidity rate of 0.5 ―1.0%. Despite the etiological complexities of schizophrenia, accumulating evidence suggests that glutamatergic disturbances, inflammation, and alterations in one-carbon metabolism might play key roles in the pathophysiologies of schizophrenia, which in turn helps us identify novel therapeutic targets. In this session, we will present our latest preclinical and human research findings to discuss novel therapeutic strategies for treatment of schizophrenia and associated psychiatric conditions.

Sat. Oct 12, 2019 8:40 AM - 10:20 AM Room 12 (503)

Organizer / Chair: ‌Suresh SUNDRAM (Department of Psychiatry, School of Clinical Sciences, Monash University and Monash Health, Australia), Co-chair: Toshiya MURAI (Department of Psychiatry, Graduate School of Medicine, Kyoto University, Japan), Discussant: ‌Kyung Joon MIN (Department of Psychiatry, Chung-Ang University, Korea)

The global increase in the awareness of mental health has coincided with the revolution of precision medicine and the possibility of personalised treatments. These advances have been absent in psychiatry due to the lack of biological markers and the imprecision of current nosologies. These shortcomings then have delayed the development of diagnostic tests and disease modifying treatments. The Asia-Pacific region is ideally placed to address these limitations due to access to large sample populations and the introduction of emergent technologies. This symposium presents varying approaches to these issues.
Sundram describes how work examining the mechanism of action of clozapine has identified epidermal growth factor system dysfunction that extends beyond treatment resistant schizophrenia to include a sub-group of mood disorder patients. Si presents research examining how multiple approaches can converge to assist understanding of the effects of antipsychotic drugs on neurodevelopment and the implications for adult behaviour. Srisurapanont presents clinical work demonstrating the differences in phenomenology based on cultural and ethnic factors that potentially influence the taxonomy of mood disorders.
Together, these presentations highlight the diversities of approaches across the region that can be brought to bear on developing new avenues in diagnosing and treating psychiatric disorders.

Sat. Oct 12, 2019 8:40 AM - 10:20 AM Room 14 (Palace Room A)

Organizer / Chair: Cheng-Ta LI (Department of Psychiatry, Taipei Veterans General Hospital. Taiwan), Co-chair: Yasushi ISHIDA (Department of Psychiatry, Faculty of Medicine, University of Miyazaki, Japan), Discussant: ‌Satoshi UKAI (Department of Neuropsychiatry, Wakayama Medical University, Japan)

A growing number of evidence points out that abnormal brain function plays an critical role in many neuropsychiatric disorders (e.g., major depression, schizophrenia, Alzheimer's disease). In addition, many of these diesase left unsatisfactorily treated even under the combination of medications and psychotherapy. In addition to electroconvulsive therapy (ECT) and traditional brain stimulation - repetitive transcranial magnetic stimulation (rTMS), a new form of brain stimulations,theta burst stimulation (TBS), is becoming more and more important in the treatment for these neuropsychiatric disorders. In 2008, US FDA cleared the rTMS system for treating antidepressant-resistant major depression; likewise, in 2018, Taiwan FDA also had rTMS approved for treating antidepressant-resistant major depression. However, what are the mechanisms underlying the brain stimulation techniques for neuropsychiatric disorders and whether TBS are more effective than traditional TMS for treating neuropsychiartic disorders (e.g., drug-resistant depression) remain not totally understood. In this symposium, experts from different countries would talk about the mechanisms and clinical efficacy of different brain stimulation techniques and the applications of brain stimulations.

Sat. Oct 12, 2019 8:40 AM - 10:20 AM Room 15 (Palace Room B)

Organizer / Chair: Norio OZAKI (Department of Psychiatry, Nagoya University Graduate School of Medicine, Japan), Co-chair: Makoto ARAI (Tokyo Metropolitan Institute of Medical Science, Japan), Discussant: ‌Tomiki SUMIYOSHI (National Center of Neurology and Psychiatry, Japan)

Early detection and new intervention are vital in psychiatric disorders. In this symposium, four speakers will discuss the recent findings of early detection and new intervention in psychiatric disorders, ranging from rare diseases, schizophrenia, to dementia. Dr. Norio Ozaki (Nagoya University, Japan) will discuss the recent findings on elucidation of pathogenesis and developement of treatment from rare susceptilibity variants of neurodeveopmental disorders such as schizophrenia and autism spectrum disorder. Dr. Yong-Chul Chung (Chonbuk National University, Korea) will review literatures on rumination in relation to psychosis and depression and its mediating role in the development of diverse psychiatric symptoms. In addition, results on the correlations between rumination and other psychiatric symptoms measured at baseline in patients with first episode psychosis (n=440), changes of rumination score at 6 and 12 ms, and its predicting role for outcome will be presented. Based on these findings, a new perspective on the efficacy of antipsychotics on rumination will be suggested.
Dr. Hsien-Yuan Lane (China Medical University, Taiwan) will report some novel N-methyl-D-aspartate receptor (NMDAR)-related biomarkers and enhancers for diagnosis and treatment of schizophrenia in this symposium. Glutamatergic system plays a key role in pathophysiology of a number of neuropsychiatric disorders including psychiatric disorders and neurodegenerative disorders. Therefore, glutamatergic system would be the novel target for these disorders. NMDAR dysfunction plays vital roles in pathogenesis of schizophrenia. However, there have been lack of suitable biomarkers and enhancers for schizophrenia. Dr. Chieh-Hsin Lin (Kaohsiung Chang Gung Memorial Hospital, Taiwan) will talk about the clinical efficacy and safety of a D-amino acid oxidase (DAAO) in the treatment of early-phase dementia. NMDAR hypofunction is found in early-phase dementia. Current treatments for dementia are unsatisfactory. Further, feasible biomarkers for detecting dementia are also lacking. DAAO inhibitor may enhance the NMDAR neurotransmission. She also found that the peripheral DAAO levels may increase with age-related cognitive decline. The findings will help to develop novel detection and intervention at early phase of dementia.
Dr. Tomiki Sumiyoshi (National Center of Neurology and Psychiatry, Japan) will conclude the session by summarizing the information presented by the speakers, and providing an insight into the development of effective ways to intervene into the early and prodromal stages of these psychiatric conditions.

Sat. Oct 12, 2019 8:40 AM - 10:20 AM Room 16 (Heian)

Organizer / Chair: Jinsong TANG (Department of Psychiatry, The Second Xiangya Hospital of Central South University, China), Co-chair: Hiroaki TOMITA (Department of Psychiatry, Graduate School of Medicine, Tohoku University, Japan), Discussants: ‌Lulin DAI (Department of Information Science and Biomedical Engineering of Kagoshima University, Japan), Yanhui LIAO (Mental Health Institute, The Second Xiangya Hospital of Central South University, China)

Schizophrenia is a severe, highly heritable, neuropsychiatric disorder. Previous studies on the relationship between interindividual variations in impulsivity and those in local brain structure in healthy subjects have yielded inconsistent findings. Our study aimed to clarify this issue using high-quality structural magnetic resonance imaging (MRI) data from 1105 healthy young adults to calculate gray matter volume (GMV). Delay discounting was used to assess impulsivity. We found significant positive correlations between area-under-the-curve (AUC) measures of delay discounting and GMV in the bilateral temporal pole, i.e., individuals with smaller GMV in the temporal pole exhibited greater delay discounting (greater impulsivity), which suggest that interindividual differences in impulsivity are associated with temporal pole morphology. These findings may provide insight into the mechanisms of impulsive behavior in clinical populations.
In addition to impulsivity, schizophrenia patients often experience auditory verbal hallucination (AVHs) and most of the AVHs usually associate with the negative evaluation of patients. AVHs can also be found in other subjects, from healthy individual to various psychiatric disorders (such as bipolar disorder, major depression disorder, post traumatic stress disorder etc). The commonality and specificity of AVHs among different subjects (including healthy individuals and patients with various mental disorders) diseases have not yet been fully described. These problems affecting the early precise diagnosis and treatment for this disease AVHs in different subjects. We suggest that using machine learning combined with neuro-imaging -genetics will be used to explore the commonality and specificity of neuro-imaging -genetics features in AVHs among patients subjects with schizophrenia, bipolar disorder, other disorders and healthy individuals with non-mental verbal hallucination. Understanding these features may reveal precise therapeutic targets, establish create the early diagnosis and precisely treatment predictive models for AVHs, establish objective index system for evaluating therapeutic outcomes, improve the early efficacy of diagnosis and treatment outcome of AVHs subjects, and to reduce the harmfulness of AVHs.
For the majority of schizophrenia patients, especially with AVHs, symptoms are treated with antipsychotic drugs such as risperidone, which has neurotransmitter receptor affinities of dopamine, serotonin and other transmitters and effective in treatment of acute psychosis and relapse prevention schizophrenia. There is a need to identify biomarkers for predicting, tracking and understanding psychopharmacological treatment outcomes. DNA methylation has been studied as a biomarker in schizophrenia risk. However, effects of antipsychotic medications on methylation have not been systematically examined. To estimate the effect of risperidone on DNA methylation, and investigate the relationship between DNA methylation changes and therapeutic effects on behavioral and neuroimaging phenotypes, this study conducted a longitudinal analysis of blood DNA methylation with 38 first-episode drug-naïve schizophrenia patients (FESPs) studied before and after risperidone monotherapy, and 38 demographically-matched healthy control individuals. We identified 8,204 FESPs associated CpG sites which enriched in brain related pathways. Risperidone treatment lead to methylation alterations of 6,143 CpG sites which are related to the calcium signaling pathway. Treatment normalized 659 CpG sites and these DNA methylation changes were related to alterations in symptoms severity, spontaneous brain physiological activity and cognitive function in FESPs.

Sat. Oct 12, 2019 10:30 AM - 12:10 PM Room 1 (Main Hall)

Chairs: ‌Junko SATO (Pharmaceuticals and Medical Devices Agency, Japan), Shigeto YAMAWAKI (Center for Brain, Mind and KANSEI Sciences Research, Hiroshima University, Japan), Discussant: ‌Tetsuo NAKABAYASHI (Pharmaceuticals and Medical Devices Agency, Japan)

Primary role of regulatory agency is to protect public health through scientific evaluation of drug and biologic products and also medical devices. To ensure the efficacy and safety of medical products based on substantial evidence, regulatory science has grown out of the need to integrate knowledge among basic research, clinical research and clinical medicine. Based on such enormous efforts and experiences on scientific evaluation, regulatory agencies can generate state-of-the-art strategies in the area of regulatory science to accelerate drug development process by making it more adequate and efficient. With greater knowledge about the direction favored by regulatory agencies, researchers and companies can design technologies. Regarding psychiatric fields, there have been many alterations in drug development programs in the past, including the mental disorders studied and complexity of clinical trial designs and data analysis. Such progress results from current advance of research for functional mechanism that underlies central nervous system (CNS) derangement in psychiatric illness. However, there is vast unmet medical need that treatment for patients with mental disorder does not result improvement sufficiently and they often disabled despite existing treatments. These situations can be accounted for in part by increasing diversity in the patients in clinical practice and existing medical products with a limited number of new mechanisms of action, and it is necessary to develop new drugs in the future. Innovative ways to quantify human and animal behavior provide increasing number of CNS targets which may contribute to psychiatric drug development, though it still remains unclear how they relate to symptoms which underlie clinical entities. From this point of view, building regulatory collaboration is strategic activity to foster potentially valuable pharmaceutical technologies and to address public health problems. The objectives of this symposium are discussion for ways of regulatory collaboration after consideration of challenges of regulatory advance for innovation.

Sat. Oct 12, 2019 10:30 AM - 12:10 PM Room 12 (503)

Organizer / Chair: ‌Hitoshi HASHIMOTO (Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Japan), Co-chair: Hirokazu HIRAI (Department of Neurophysiology & Neural Repair, Gunma University Graduate School of Medicine, Japan), Discussants: ‌Tomoyuki FURUYASHIKI (Division of Pharmacology, Graduate School of Medicine, Kobe University, Japan), Tetsuya SUHARA (National Institutes for Quantum and Radiological Science and Technology, Japan)

The habenula is a small brain region located close to the midline and surrounded by the third ventricle and is well conserved across vertebrates. It has this name from Latin for "little rein" which was originally designated as pedunculus of pineal body and thought to be involved in regulation of the pineal gland. However, recently studies have demonstrated that the habenula connects various brain regions within, e.g., the forebrain and midbrain and is implicated in a variety of important brain functions. The habenula is divided into two main subregions, the medial and lateral habenula (in lower vertebrates, dorsal and ventral habenula). These two subregions have been shown to have distinct composition of neurotransmitters, neural connectivity, and gene expression profiles. More recently, a number of important findings have been reported that illustrate the critical roles of the habenula in emotional regulation, disturbance of which can cause psychiatric disorders such as depression, and thus provide insights into new treatment approach. In this symposium, three eminent guest speakers will present their recent research achievements concerning the roles of the habenula. Dr. Hitoshi Okamoto at RIKEN will present the findings showing that social conflict and aversive behavior are regulated by the habenula using zebrafish. Dr. Hidenori Aizawa at Hiroshima University will present the findings showing that aberrant glial function in the lateral habenula is involved in the increased susceptibility to the chronic stress. Dr. Yihui Cui at Zhejiang University will present the findings showing that ketamine blocks bursting in the lateral habenula providing a possible mechanism for rapid antidepressant actions.
(This symposium will be related with those organized by Dr. Kenji Hashimoto (S37) and Dr. Tung-Ping Su (S15).)

Sat. Oct 12, 2019 10:30 AM - 12:10 PM Room 14 (Palace Room A)

Organizer / Chair: Shih-Ku LIN (Taipei City Hospital and Psychiatric Center, Taiwan), Discussants: ‌Chay Hoon TAN (National University of Singapore, Singapore), Andi Jayalangkara TANRA (Universitas Hasanuddin, Indonesia)

REAP is the longest standing and the largest international collaborating research in the field of psychiatry in Asia. The study started in 1999 as a large scale collaborative research project in East Asia. The REAP studied the prescription of patients with schizophrenia in 2001, 2004, 2008 and 2016. Fifteen countries and areas in Asia participated in the REAP survey in 2016. More than seventy papers were published from this consortium.
The first survey of bipolar disorder is implemented in 2018. In this symposium, Prof Shinfuku will give an overview talk on REAP and its clinical implication and influence; Prof Inada will discuss the use of Dug-induced Extrapyramidal Symptoms Scale in REAP AP4; Prof Chong will discuss multiple versus single antipsychotic drug treatment of inpatients with schizophrenia; and Prof Lin will report the findings from REAP Bipolar disorder.

Sat. Oct 12, 2019 10:30 AM - 12:10 PM Room 15 (Palace Room B)

Organizer / Chair: Toshi A. FURUKAWA (Department of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Japan), Co-chair: Hisateru TACHIMORI (National Center of Psychiatry and Neurology, Japan), Discussant: ‌Fumihiro TAMURA (Meiji Seika Pharma Co., Ltd., Japan)

Medicine is making constant progress and for many diseases we currently have several or more treatment alternatives. Network meta-analysis (NMA) offers the strongest method for evidence synthesis in such circumstances by pooling both direct and indirect comparisons, thus enabling comparisons where direct ones are lacking, making effect estimates more precise than through direct comparisons only, and ultimately ranking all alternative treatments.
The methodology of NMA is making steady progress. We can now pool individual participant data (IPD) in NMA, which enables more consistent and more precise comparisons and also detection of effect modifiers and prognostic factors for alternative treatments. The results then can contribute to stratified or personalized medical care. NMA can also be conducted cumulatively or sequentially, which will enable up-to-date evidence synthesis.
This symposium will showcase the cutting edge examples of modern NMA and its developments.

Sat. Oct 12, 2019 10:30 AM - 12:10 PM Room 16 (Heian)

Organizer / Chair: Takahiro KATO (Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Japan), Co-chair: Po-See CHEN (Department of Psychiatry, College of Medicine, National Cheng Kung University, Taiwan), Discussants: ‌Masahiro OHGIDANI (Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Japan), Eiji SHIGETOMI (Department of Neuropharmacology, University of Yamanashi, Japan)

Glial cells including astrocytes and microglia have recently been highlighted in the field of neuropsychiatry. Human postmortem and PET studies have suggested that activation of glial cells contribute to developing psychopathology in a variety of psychiatric disorders such as delirium, epilepsy, schizophrenia, mood disorders and autism. However, deeper molecular mechanisms have not been well clarified. Tradittionaly, actions of psychotropic drugs had been believed to be limited to neurons and synapses, and glia-target drugs are warranted. On the other hand, underlying mechanisms of non-pharmacological treatments such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) have not been clarified, and we hypothesize that glial cells may strongly contribute to the action of these treatments. By the way, delirium has been suggested as a glia-oriented disease, and deeper understandings of delirium will clarify the roles of glia not only in delirium but also in many other psychiatric disorders.
In order to discuss/resolve the above highly-important topics in glia-psycho-pathology, four speakers will introduce the up-to-knowledge based on their own study from rodent in vitro and in vivo experiments to human epigenetic and blood molecular approaches.
Prof. Koizumi will introduce the novel pharmacological actions of antidepressants on glial cells using rodent models. Dr. Limoa will talk about the possible glia-modulating mechanisms of ECT based on a rat model. Dr. Shinozaki will introduce his novel translational research of delirium patients focusing on epigenetics of glia. Finally, Dr. Kato will introduce a novel translational research approach using human blood samples such as metabolomic analysis and also a human blood induced microglia-like (iMG) cells to clarify the dynamic interaction between molecular actions and severity of psychiatric symptoms.
We believe that our symposium will shed new light on the future development of glia-target therapy in psychiatry.

Sat. Oct 12, 2019 10:30 AM - 12:10 PM Room 17 (Suehiro)

Organizer / Chair: ‌‌Gavin Stewart DAWE (‌Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore), Co-chair: Masaki TANAKA (Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Japan)/ Masabumi MINAMI (Department of Pharmacology, Graduate School of Pharmaceutical Science, Hokkaido University, Japan), Discussant: ‌Toshihisa OTSUKA (Department of Biochemistry, Graduate School of Medicine / Faculty of Medicine, University of Yamanashi, Japan)

Relaxin-3, an relaxin/insulin-like family peptide, and its receptor RXFP3 have been proposed to modulate emotional-behavioural functions such as arousal and behavioural activation, appetite regulation, stress responses, anxiety, memory, sleep and circadian rhythm. Relaxin-3 is expressed primarily in the brain where it is found most prominently neurones of the nucleus incertus (NI). The NI in the midline tegmentum close to the fourth ventricle projects widely throughout the brain. Over recent years, a number of preclinical studies have explored the function of the NI and relaxin-3 signalling, including reports of mRNA or peptide expression changes in the NI in response to behavioural or pharmacological manipulations, effects of lesions or electrical or pharmacological manipulations of the NI, effects of central microinfusions of relaxin-3 or related agonist or antagonist ligands on physiology and behaviour, and the impact of relaxin-3 gene deletion or knockdown. Together the available evidence suggests that targeting the nucleus incertus network and relaxin-3/RXFP3 system may be novel therapeutic approach in neuropsychiatric disorders including anxiety disorders, depression, and eating disorders. This symposium will explore the most recent evidence indicating that the relaxin-3/RXFP3 system may be novel therapeutic target for neuropsychiatric disorders and advances in the development of ligands for the RXFP3 receptor.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 1 (Main Hall)

Chairs: ‌Makoto SUEMATSU (Japan Agency for Medical Research and Development, Japan), Shigeo OKABE (Dept. of Neurobiology, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan), Discussant: ‌George F. KOOB (National Institute on Alcohol Abuse and Alcoholism, USA)

Since Japan has now become a super-aged society, there is a strong demand for revealing the pathogenesis of neuropsychiatric disorders and developing the fundamental treatments for these conditions.
Based on the plan for the Promotion of Medical Research and Development prescribed by the government of Japan, the Medical Research and Development (AMED) promotes integrated R&D in the field of medicine, from basic research to clinical trials, focusing on interrelated areas including neuropsychiatric conditions. In addition to ensuring that outcomes are linked through practical application, it undertakes projects with the aim of comprehensively and effectively establishing and maintaining an environment for this R&D.
The Project for Psychiatric and Neurological Disorders accelerates endeavors aiming to overcome dementia, depression, and other brain disorders. The goal of this project is to establish innovative strategies for diagnosis, prevention, and treatment of brain disorders through the strong promotion of research on neural circuits and brain functions related to the pathophysiology of the brain.
In this symposium, four presenters will discuss the current issues and the future direction of basic and clinical brain science research in Japan.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 6 (401+402)

Organizer / Chair: ‌Toshikazu SAITO (Miki Mental Clinic / Department of Psychiatry, Sapporo Medical Univesity, Japan), Discussants: ‌Sungwon ROH (Department of Psychiatry, Hanyang University College of Medicine, Korea), Tony Szu-Hsien LEE (Department of Health Promotion and Health Education, National Taiwan Normal University, Taiwan)

Alcohol and drug abuse is a serious public health problem among Asian countries that affects almost every community. The magnitude of problems and situations of alcohol and drug use as well as addictive disorders differ country by country, due to such region-specific aspects as the components of the community and cultural differences. Dealing with such problems in various countries is aimed to clarify the region-specific aspects of problems in addiction in countries’ context, thereby contributing to delineate the issue and further to develop a better understanding of the problems and management. Addressing and solving these problems requires information from research that is specific to the context of the society.
As mentioned above, we plan to make a symposium titled “Early career researchers symposium: Clinical research in progress on addictive medicine”. This symposium aims to highlight research projects in the addictive field that investigated by young international researchers. It will focus on different types of clinical research projects that young researchers are conducting them including observational studies, clinical trials, and data analyses. Each participant will share their research projects in development, describe their aims, methods, preliminary data, and future goals of the research projects. The presentations include some evidence supporting the biopsychosocial model of addiction, which focus on both in neurobiological and psychosocial findings on understanding the situations of the problems, the progression, and the outcome of addictive behaviors, including some parts of management among the different countries.
Furthermore, this symposium will show that initiating research projects is a challenging task for a young researcher, particularly the limited time and funding. It will also demonstrate some of the key elements of developing a successful research project including finding adequate mentorship, building a research team, and working through the obstacles during conducting the research projects. We hope that the symposium attendances will understand the problems of drug addiction in this region. This will lead to the more in-depth discussion of this issue and further collaboration for further researches in the future.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 11 (502)

Organizer / Chair: ‌Chan-Hyung KIM (Department of Psychiatry, Yonsei University College of Medicine, Korea), Discussants: ‌Toshihide KUROKI (Department of Clinical Psychology, Kyushu University Graduate School of Human-Environment Studies, Japan), Taro KATO (Pharmacology Research Unit, Sumitomo Dainippon Pharma Co., Ltd., Japan)

Obsessive-compulsive (OC) symptoms are remarkably diverse, and the clinical presentations can vary both within and across patients over long period of time. This variability in the phenotypic expression has led to the hypothesis that obsessive-compulsive disorder (OCD) is a heterogeneous disorder and that this heterogeneity obscures the findings of clinical, natural history and treatment response studies. OCD is commonly considered as a heterogeneous condition with distinct neural correlates across symptom dimension. The precise causal factors for OCD are not known, however, decades of research have proposed abnormalities of cortico-striatal circuits that involve the orbitofrontal cortex, anterior cingulate cortex, thalamus and the striatum in the brain as a critical pathway involved in obsessions and the intimately linked compulsive-repetitive behaviors. A complete understanding of what comprises OCD will require a several different approaches. These approaches include (1) narrowing the phenotype to identify neurobiological basis of individual phenotypes in OCD (2) broadening the phenotype in OCD to include hoarding disorder (3) updating recent non-invasive treatment technique, such as neuromodulation for OCD and (4) challenging to manage OCD comorbid with schizophrenia and bipolar disorder, difficult-to-treat. it is hoped that the characterization of the pathophysiological mechanisms of OCD components and OC related conditions could contribute to the development of specific pharmacological and neuromodulatory therapies tailored to each of these conditions.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 12 (503)

Organizer / Chair: ‌Yen Kuang YANG (Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan), Co-chair: Toshiya MURAI (Department of Psychiatry, Graduate School of Medicine, Kyoto University, Japan), Discussants: ‌Fumitoshi KODAKA (Department of Psychiatry, The Jikei University School of Medicine, Japan), Shinsuke KOIKE (Center for Evolutionary Cognitive Science, The University of Tokyo, Japan)

In light of the advance of clinical neuro-imaging, several new techniques and constructs have been introduced to lift the veil of schizophrenia on varying levels (e.g., brain volumetric changes, resting-state connectivity, deep learning, and endophenotype). However, the results for guiding on improving clinical practice in treating patients with schizophrenia are still uncertain. There are several novelty efforts for this gap will be presented in this proposed symposium. Four proposed talks will be presented in this symposium. Firstly, fMRI data (T1, resting, task-based data) of first episode psychosis (n=140) with deep learning methods will be presented and its application for how to apply/improve clinical practice will be discussed. Secondly, although dopamine hypothesis for schizophrenia had been proposed for many decades, however the role of dopamine in prognosis of schizophrenia is still debated. Some of the studies to explore dopamine level based on drug naïve patients showed higher DA level could be, compared with their controls. However, does higher DA activity mean trait of schizophrenia in the early phase of illness? The meta-analysis showed controversy result. The possible explanation for the DA role in the pathogenesis in schizophrenia will be proposed in the report. Additionally, it was well known that the deficit/negative symptoms were caused by hypodopaminergic activities. Does DA activity of drug naive patients with schizophrenia predict outcome? This second part of symposium will show higher dopaminergic activities in the drug naïve patient will show better prognosis in their 8-year follow-up study. Besides, the correlation of dopamine availability and volumetric changes in drug naïve patient will be presented and their clinical application will be discussed. Thirdly, a leading hypothesis regarding the etiology of schizophrenia emphasizes the pivotal role of dysfunctional self in its various manifest symptoms. In support of the hypothesis, a reliable link between atypical self-representation and psychosis has been documented in empirical studies in patients with schizophrenia, other patients with positive psychotic features, and subclinical individuals with psychotic-like experiences. Yet, it has been largely unknown about the specificity of this link. Atypical self-representation may fuel other psychiatric dysfunctions as well as psychosis. Failing to recognize the heterogeneous outcomes of dysfunctional self-representation hence increases the risk for an over-inclusive framework of psychosis, leading to the low predictive power of the dysfunctional self-representation endophenotype for psychotic disorders. It is crucial to systematically investigate self-representation in studying early phase psychosis. Finally, traumatic experience has been shown to be reliable environmental risk factor for schizophrenia, despite the lack of an account for its precise pathogenic mechanism. The final part of this symposium will focus on the relationship between traumatic experience and volumetric changes in patients with schizophrenia.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 13 (501)

Organizer / Chair: Kenji HASHIMOTO (Chiba University Center for Forensic Mental Health, Chiba, Japan), Co-chair: Edward DOMINO (Department of Pharmacology, University of Michigan, USA), Discussants: ‌Tung-Ping T SU (Department of Psychiatry, Cheng-Hsin General Hospital, National Yang-Ming University, Taiwan), Shigeyuki CHAKI (Research Headquarters, Taisho Pharmaceutical Co., Ltd., Japan)

The N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is a popular abused drug in the world including Asia. In contrast, ketamine is one of the most attractive antidepressants since ketamine can produce rapid-onset and sustained antidepressant effects in treatment-resistant patients with major depression and bipolar disorder. A number of clinical studies make ketamine an attractive rapid-onset therapeutic drug for treatment-resistant depression, although its clinical application may be limited owing to its propensity of causing psychotomimetic effects and abuse liability. The four speakers of this symposium are ketamine research experts in Asia.
Substance addiction has long been associated with dysregulation in stress response systems. Dr. Ming-Chyl Huang (Taiwan) presents the alterations of orexin-A, oxytocin, ACTH, and cortisol levels in treatment-seeking ketamine-dependent patients before and after early abstinence. Chronic ketamine abuse is associated with an abnormal expression of stress-related neuropeptides, which do not normalize after ketamine discontinuation. Those with an anxious phenotype might have a more disrupted stress regulation. These results could provide insight into the development of potential therapeutic strategies to treat ketamine dependence.
Low-dose ketamine has rapid antidepressant effects and brings new hope for patients with treatment-resistant depression. However, while it looks promising, there are still some potential issues unsolved which need to be clarified. Dr. Cheng-Ta Li (Taiwan) would focus not only the positive findings on it but also some potential problems to see while using this compound clinically.
Ketamine (Ki = 500 nM for NMDAR) is a racemic mixture containing equal parts of (S)-ketamine (Ki = 300 nM) and (R)-ketamine (Ki = 1400 nM). Interestingly, (R)-ketamine showed greater potency and longer lasting antidepressant effects than (S)-ketamine in several animal models of depression. Accumulating evidence suggest that gut microbiota may play a role in depression and in the antidepressant effects of certain compounds. Dr. Chun Yang (China) will talk about the role of gut-microbiota in the antidepressant effects of ketamine and its two enantiomers (R)-ketamine and (S)-ketamine. (R)-ketamine is metabolized to (2R,6R)-hydroxynorketamine (HNK) in the liver. Finally, Dr. Kenji Hashimoto (Japan) will talk the recent findings of (R)-ketamine and its metabolite (2R,6R)-HNK in animal models of depression. In this symposium, we discuss the benefits and risks of ketamine and its enantiomers in the treatment of depression.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 14 (Palace Room A)

Organizer / Chair: ‌Atsufumi KAWABATA (Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Japan), Co-chair: Masako ISEKI (Department of Anesthesiology and Pain Medicine, Juntendo University School of Medicine, Japan), Discussants: ‌Katsuo TOIDE (Neuroscience Drug Discovery Consulting, Japan), Fumiko SEKIGUCHI (Laboratory of Pharmacology and Pathophysiology, Faculty of Pharmacy, Kindai University, Japan)

Accumulating evidence has unveiled the critical roles of neuroinflammation, particularly related to innate immune responses, in diverse neurological disorders. A variety of damage-associated molecular patterns (DAMPs)/alarmins, released endogenously from host cells, interact with pattern recognition receptors (PRRs), thereby promoting inflammation throughout the mammalian body including the brain. High mobility group box 1 (HMGB1), one of the best known DAMPs/alarmins, is now considered to play a crucial role in the development of neuroinflammation, which is associated with stroke, dementia, epilepsy, neuropathic pain, etc. Prothymosin alpha regulates the neuroimmune systems as a unique member of DAMPs/alarmins. Toll-like receptors (TLRs), the best known PRRs, recognize a variety of DAMPs/alarmins, in addition to pathogen-associated molecular patterns (PAMPs), and participate in the pathogenesis of diverse neurological disorders. In this symposium, four speakers will focus on DAMPs/alarmins and PRRs in the neuronal systems, which are essential for the pathogenesis of neurological disorders, innovation of the therapeutic strategies and development of the biomarkers. Dr. Hsueh, one of the most active female researchers in Taiwan, will speak about the role of PRRs, particularly TLRs, in regulation of neuronal morphology and function in relation to neurodevelopmental disorders including autism spectrum disorders, schizophrenia, attention deficient hyperactivity disorder (ADHD), mental retardation, etc. Dr. Okazawa will focus on DAMPs/alarmins-mediated pathologies in dementia including Alzheimer’s disease. Dr. Ueda will show the unique molecular mechanism for extracellular release of prothymosin alpha, one of neuroprotective DAMPs/alarmins. Finally, Dr. Kawabata will talk about the role of HMGB1 and PRRs including the receptor of advanced glycation end-products (RAGE), TLRs and chemokine receptors in the pathogenesis of neuropathic pain. In this symposium, we believe that basic researchers, clinical neuroscientists, physicians, employees of pharmaceutical companies, etc. will learn the cutting-edge information concerning the roles of DAMPs/alarmins and PRRs in diverse neurological disorders, which will contribute to the development of novel therapeutic strategies in future.

Sat. Oct 12, 2019 2:50 PM - 4:30 PM Room 15 (Palace Room B)

Organizer / Chair: ‌Brian DEAN (Florey Institute for Neuroscience and Mental Health / Centre for Mental Health, Swinburne University, Australia), Co-chair: Takeo YOSHIKAWA (RIKEN Center for Brain Science, Japan), Discussant: ‌Akinori NISHI (Department of Pharmacology, Kurume University School of Medicine, Japan)

Psychiatric disorders are complex and occur in individuals with a genetic predisposition following an encounter with deleterious environmental factors. The interaction between environment and the genome occurs through epigenetic mechanisms and the outcome is to cause changes in gene expression. This knowledge underpins the ongoing use of human postmortem CNS to understand the pathophysiologies of psychiatric disorders by identifying the changes in molecular cytoarchitecture brought about by changed gene expression. In Japan efforts are being made to create a Network of Brain Banks that will include tissue from subjects with psychiatric disorders. However, there is already collaborations between Japanese scientists and the Melbourne Psychiatric Brain Bank that are shedding light on the pathophysiology of psychiatric disorders. The objective of this symposium is to update delegates on outcomes from the study of brain tissue from the brain bank and how they are advancing knowledge on the molecular pathology of psychiatric disorders. The first speaker, Brian Dean, will provide a brief description of the Melbourne Psychiatric Brain Bank and will then review how recent studies of the cortical human transcriptome using tissue from the Brain Bank are providing new information on the underlying pathophysiologies of schizophrenia, major depressive disorders and bipolar disorders. Whilst such transcriptomics data are increasing knowledge of the potential causes of psychiatric disorders, the challenge remains as to how such “omics” data can be interpreted. Hence, the second presenter, Hirotaka Sekiguchi, will present new data on changes in levels of the cortical and sub-cortical dopamine transporter in schizophrenia and mood disorders. These data will be used to suggest mechanisms by which changes in dopamine homeostasis is involved in the pathophysiologies of schizophrenia and major depressive disorders. The final two speakers in the Symposium will focus on changes in lipid metabolism in the corpus callosum from subjects with schizophrenia. Neuroimaging studies have suggested changes in the corpus callosum are particularly prevalent in schizophrenia. The corpus callosum is the bridge between the brain hemispheres containing wide thick nerve tracks. Hence, changes in the functioning of lipids such as phospholipids and sphingolipids in this CNS region would have profound effects on CNS function. Hence, the third speaker, Chie Shimamoto-Mitsuyama, will review evidence that suggests changed lipid metabolism may be present in the corpus callosum from subjects with schizophrenia. The Symposium will close with the forth speaker, Kayoko Esaki, who will argue there is changes in the regulation of sphingolipid-signaling pathway in the corpus callosum from schizophrenia. In conclusion, this symposium will provide an update to the delegates at AsCNP on new findings, predominantly by young Japanese scientists, on the molecular pathophysiologies of schizophrenia and mood disorders.

Sun. Oct 13, 2019 8:40 AM - 10:20 AM Room 1 (Main Hall)

Organizer / Chair: Tetsurou KIKUCHI (New Drug Research Division, Pharmaceutical Business Division, Otsuka Pharmaceutical Co., Ltd.), Co-chair: George KOOB (National Institute on Alcohol Abuse and Alcoholism, USA)

Sixty years have passed since the antipsychotic effects of chlorpromazine and the antidepressant effects of imipramine were discovered in the 1950s. Since then, many antipsychotics and antidepressants have been studied and developed, based on the excessive dopamine hypothesis of schizophrenia and monoamine hypothesis of depression. Regarding antipsychotic drugs, several studies have clarified that the action mechanism of typical antipsychotic drugs was dopamine D2 receptor antagonist. Subsequently, other agents were also developed, such as serotonin-dopamine antagonist (SDA) and dopamine D2 receptor partial agonist. These drugs succeeded in alleviating extrapyramidal symptoms and in overcoming excessive sedative actions and hyperprolactinemia among issues caused by the use of typical antipsychotic drugs. However, their clinical effects are insufficient, and the development of excellent antipsychotic drugs that can effectively alleviate the negative symptoms and cognitive dysfunctions are awaited. Regarding antidepressants, some studies have elucidated that the action mechanisms of imipramine are serotonin and noradrenalin reuptake inhibition. With imipramine as a starter, tricyclic and tetracyclic antidepressants were developed. After these, in the pursuit of drugs that ensure the efficacy of tricyclic antidepressants and eliminate adverse events, drugs were developed such as selective serotonin reuptake inhibitor (SSRI), which selectively inhibits the reuptake of serotonin, and serotonin-norepinephrine reuptake inhibitor (SNRI). In addition, tetracyclic antidepressants developments led to noradrenergic and specific serotonergic antidepressant (NaSSA), which does not inhibit monoamine reuptake. However, antidepressants with a fast onset of effect and a more powerful clinical effect remain awaited. Looking at the treatment of neurological diseases, particularly of Alzheimer-type dementia, successful developments were made in drugs that improve symptoms, such as cholinesterase inhibitor and NMDA receptor antagonist. However, all the other developments made in many chemical compounds with other action mechanisms have resulted in failure in clinical trials.
Under these circumstances, we planned this symposium to provide information about some noteworthy new drugs for treating psychiatric and neurological diseases that are based on new action mechanisms. We hope that this project will help global researchers to gain insights into drug development. We also strongly hope that these drugs with new action mechanisms will be approved and marketed to provide new therapeutic values for patients. We expect that the understanding of the basic pathology of relevant neuropsychiatric diseases can be deepened through research on the relationship between “new action mechanism” and “observed clinical effect” in the future.

*Presentations of this symposium are also presented as posters.
Poster No.: DDR-1 ~ DDR-11
Poster display: October 11 (Fri) – 13 (Sun)
Poster discussion: October 13 (Sun) 16:40 – 18:10
Venue: Poster Hall (Fukuoka International Congress Center, 2F, Multi-purpose Hall).