Resting-state functional brain network is defined as temporal correlations between BOLD signals of many brain areas measured by fMRI. Disorder specific abnormal patterns were found in this rs-fcMRI (resting state functional connectivity magnetic resonance imaging) , thus biomarkers of several disorders have been developed based on rs-fcMRI. However, previous biomarkers did not generalize well beyond a single imaging site. We developed a new machine learning technique by combining L1-regularized canonical correlation analysis and sparse logistic regression so that the biomarker achieved more than 80% correct rate for multiple Japanese sites, and the biomarker developed only using Japanese data generalized for US data with more than 70% correct rate (Yahata et al. 2013) . fMRI real-time neurofeedback had been applied as a new therapy for chronic central pain, depression and compulsive disorders. Shibata et al. (2011) developed the “decoded neurofeedback” (DecNef) method by which specific brain activity patterns can be induced noninvasively utilizing fMRI real-time neurofeedback. It is possible to combine the above mentioned biomarker and DecNef to construct a new therapy for psychiatric disorders (Hashimoto et al. 2013) . We ascertained safety of this method and obtained preliminary but encouraging results showing recovery of normal brain network patterns in high-functioning adult autism spectrum disorder patients.

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Accumulating evidence that glutamatergic abnormalities have been implicated in the pathophysiology of schizophrenia and depression is opening opportunities for the development of novel therapies targeting glutamatergic systems. Among glutamate receptors, metabotropic glutamate (mGlu) receptors are of interest as therapeutic targets for schizophrenia and depression, based on pharmacological studies using their selective ligands and their distribution in the brain. In particular, recent preclinical and clinical data indicate that mGlu2/3 receptor and mGlu5 receptor could be promising targets for drug discovery for these psychiatric disorders. In addition, recent pharmacological studies show roles of mGlu4 receptor in schizophrenia. 　In this symposium, roles of above mentioned mGlu receptors in schizophrenia and depression as well as applications of ligands for mGlu receptors to treating these psychiatric disorders were presented.

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In spite of controversy on the advantage of atypical antipsychotic drugs (AAPDs) to treat cognitive impairment in schizophrenia (CIS) , substantial subsets of patients benefit from these compounds. There is extensive evidence for the ability of AAPDs of various profiles, e.g. more potent affinity for serotonin (5-HT) receptor subtypes versus dopamine (DA)-D2 receptors and actions on multi-receptors, including mGluR2/3, to enhance cognition. Therefore, further investigations are needed into the heterogeneity in response to AAPDs within patients, specific cognitive domains relevant to outcome, and the neurobiological basis for the efficacy of AAPDs in model animals. The objective of this symposium involving presentations from Italy, USA, and Japan was to provide the evidence for the development of additional therapeutics for CIS.

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[in Japanese]

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Mood disorders are not only central but also systemic disorders involving abnormalities with autonomic nervous, neuroendocrine and neuroimmune systems. Over the past decades a number of investigators have studied to find convenient and reliable blood- based biomarkers. Although changes in peripheral blood are not identical to changes in the CNS, they are known to reflect central changes. Dexamethasone suppression test and brain derived neurotrophic factor (BDNF) levels are the most established biomarkers, but not sensitive enough to be clinically useful diagnostic makers. Recent advances in genomic, genetic, epigenetic and proteomic technologies have opened a new way for biomarker study of psychiatric diseases. These new technologies enable us to measure multiple variables from a small amount of blood sample. Studies with these technologies have revealed that mood disorders show specific changes in the gene and protein expression. It has been shown that mood stabilizers and antidepressants induce multiple gene expressional changes in the peripheral leukocytes or lymphoblastoid cells. The symposium aimed to review the recent progress of blood - based biomarkers for the diagnosis and drug response for mood disorders. The four speakers from USA, Israel and Japan introduced their recent works and then had a general discussion. The symposium provided the audience a cutting edge knowledge and broad perspective in this interesting and promising field.

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This symposium addressed the pathological role of mitochondrial dysfunction and related new therapeutic perspectives in neuropsychiatric disorders. The translocator protein (18 kD) shows neuroprotective and antiinflammatory effects, and thus may be valuable for the treatment of neurologic diseases. The molecular mechanism underlying the PINK1-dependent mitochondrial translocation and activation of Parkin is an initial step of mitophagy. Prevention of activation of Parkin may be useful for treatment and diagnostic marker in the early stage of Parkinson’s disease. Neonatal MK- 801 treatment induced dysregulation in the p70S6K - S6/eIF4B pathway and protein translation in the frontal cortex of the developing rat brain, suggesting an important role of protein translation machinery in animal model of schizophrenia. Supplementation with omega-6/omrga- 3 ratio of 4/1 remarkably improved ASD symptoms and upregulation of signaling.

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We organized the symposium entitled “Rodent models targeting specific neural circuits for the study of psychiatric disorder” in WFSBP2013Kyoto. In this symposium, we focused on the use of new molecular techniques targeting neural circuits to understand molecular - circuit regulatory mechanisms which are relevant to psychiatric diseases, including schizophrenia, depression, drug addiction, and narcolepsy. Dr. Hikida presented data on the regulator y roles of dopaminergic neurons for the basal ganglia circuit, key neural substrates that control psychomotor and cognitive functions, and discuss the pathological role of this circuit in mental diseases including drug addiction. Dr. Yamanaka presented the impact of the activity of orexin- producing neurons in the hypothalamus circuit in regulation of sleep/wakefulness and the pathophysiology of narcolepsy. Dr. Kamiya presented convergent mechanisms of genetic risk factors for schizophrenia using a mouse model developed by in utero electroporation and discussed their effect on prefrontal cortex development. Dr. Russo highlighted his recent work on the epigenetic mechanisms of synaptic remodeling of nucleus accumbens neurons in depression. He identified overlapping mechanisms from rodent depression models validated in human postmortem nucleus accumbens from depressed subjects. Our studies using various in vivo manipulation techniques will provide new insights into pathological mechanisms of neuronal circuit in psychiatric disorders.

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This article reports the symposium “EEG and ERP in psychiatry - novel insights into the phenomenology, cognitive processing, and early intervention of psychosis” in WFSBP 2013. The first presenter reported the ERP study in early stages of psychotic disorders. The patients in early stages of psychotic disorders showed reduced amplitude in duration mismatch negativity, but not in frequency mismatch negativity. The second presenter reported EEG studies of the deficit syndrome. Increased slow wave during wakefulness and decreased slow wave sleep were associated with negative symptoms in schizophrenia. The third presenter reported EEG studies in decision making processes. The studies using ERP and neural oscillations revealed abnormal decision making processes in attention deficit hyperactivity disorder and substance use disorder. The fourth presenter reported the ERP study in at risk mental state. The subjects with at risk mental state who later developed schizophrenia had small mismatch negativity compared to the subjects with at risk mental state who did not develop schizophrenia. These findings suggest that EEG and ERP may be useful for elucidating the pathophysiology of psychiatric disorders and can be used as biomarkers for diagnosis and treatment.

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The symposium “Pharmacogenomics of CNS Disorders” was organized by Dr. Ramón Cacabelos of Euroespes Medical Center, and the four speakers from Japan, China, USA, and Spain presented their data of genomic research concerning CNS disorders. M.Takeda presented the translational approach for development of disease- modifying drugs against Alzheimerʻs disease. YongYong Shi from Peopleʼs Republic of China talked about genetic studies of clozapine- olanzapine- induced side- effects in the Han Chinese population. Gjumrakch Aliev, USA talked on oxidative stress - induced mitochondrial DNA overproliferation and deletion in neurodegenerative disorders. Ramon Cacabelos, Spain, talked about influence of pleiotropic genes in CNS pharmacogenomics. It is important to promote the research toward implementation of personalized medicine in which genomic data of the individual will be utilized for the better selection and better dosing of the drugs for CNS disorders. The pharmacogenomics data is expected to be especially useful for CNS disorders.

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The symposium “Immune system: The bridge between brain and mental disorders” was chaired the author, Hideki Horikawa (Kyushu University, Fukuoka, Japan) . Accumulating data have recently suggested immunological abnormalities in patients with mental disorders. Research groups from each countries have presented their latest data indicating relationships between neuroimmunology and mood disordes. In this symposium, Prof. Norbert Mueller showed the increase of proinflammatory cytokines in depression, effects of cytokines on the tryptophan - serotonin metabolism, and antidepressant effects of anti-inflammatory treatment. The author, Hideki Horikawa showed the effect of antidepressants on microglial activation in vitro. Interestingly, that effect may possibly be independent of their effect on serotonin transporter. Dr. Ruby Castilla-Puentes showed the disproportional signal for depression or suicide in patients on TNF alpha Inhibitors by using data mining techniques. The result showed that there is not increased reporting of depression and suicide for users of TNF alpha inhibitors. The presentation by Dr. Jorge Franco was cancelled. The discussion was active and fruitful, and most of the participants believe that the pathology of mood disorder cannot be explained only by monoamine dysfunction. Immunological dysfunction plays an important role in depression, and further research is needed. We hope that “Immunity: the bridge between brain and mental disorders” would also be the bridge between clinical psychiatry and biology.

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The N-methyl-D-aspartate (NMDA) receptor plays a role in the pathophysiology of schizophrenia, and the NMDA receptor is one of the most attractive therapeutic targets for this disease. In this symposium, the four speakers had discussed the role of NMDA receptor in the pathophysiology of schizophrenia and the possibility of NMDA receptor as a therapeutic target.

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