Poster

Poster 14 Mood Disorders 2 ポスター 14 気分障害2

P14-1 Eye Movement Abnormalities in Major Depressive Disorder 大うつ病性障害における眼球運動異常 Takahashi Junichi（高橋潤一）¹，三浦健一郎²，森田健太郎³，藤本美智子⁴，山森英長⁴，安田由華⁴，工藤紀子⁴，宍戸恵美子⁵，岡崎康輔⁶，笠井清登³，平野羊嗣¹，橋本亮太^4,7,8，鬼塚俊明¹ ¹Department of Neuropsychiatry Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ²Department of Integrative Brain Science, Graduate School of Medicine, Kyoto University, Kyoto, Japan ³Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan ⁴Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan ⁵Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan ⁶Department of Psychiatry, Nara Medical University, Nara, Japan ⁷Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan ⁸Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan Eye movement abnormalities of schizophrenia have been repeatedly reported; however, there are few studies on eye movements in affective disorders. In the present study, we evaluated eye movements in major depressive disorder (MDD). Thirty-five patients with MDD and 343 healthy subjects (HS) were recruited at five institutions in Japan. Free-viewing, fixation stability and smooth pursuit tests were performed, and 35 variables were calculated. Tests for group differences were conducted using a t-test, and we used p<1.43×10^-3 as the cut-off for statistical significance, considering the nature of multiple comparisons. In the free-viewing test, there were significant group differences in scanpath length (HS: 112.02±29.45, MDD: 89.99±35.34, p=4.36×10^-5), and average saccade velocity (93.61±19.38, 80.22±17.83, p=1.05×10^-4). In the fixation stability test, no significant differences were observed. In the smooth pursuit test, there were significant group differences in duration of saccades (30.83±5.55, 37.37±9.83, p=4.24×10^-4), saccade amplitude (2.05±0.61, 2.65±0.83, p=1.72×10^-4), peak saccade velocity (103.69±38.30, 149.60±53.47, p=1.58×10^-5), and horizontal velocity gain (0.84±0.10, 0.74±0.15, p=2.19×10^-4). Eye movement abnormalities were observed in patients with MDD, and may be related to the pathology of MDD. All participants provided written consent to the study after full explanation of the study procedures. Anonymity was preserved for all participants.		P14-2 A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant effects 既存抗うつ薬SSRIの作用機序と異なる新たな抗うつメカニズムの解明 Kondo Makoto（近藤誠），小山佳久，中村雪子，島田昌一 Dept. of Neurosci. and Cell Biol., Grad. Sch. of Med., Osaka Univ. Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus. Furthermore, our in vivo microdialysis analysis shows that 5HT3R regulates hippocampal extracellular IGF1 levels, and we also show that 5HT3R-dependent hippocampal neurogenesis is mediated by increased IGF1 levels. Altogether, our findings suggest a novel 5HT3R-IGF1 mechanism that is distinct from fluoxetine-induced responses and that provides a new therapeutic target for depression, especially bringing significant benefits for SSRI-resistant depressed patients.

P14-3 TMS-induced EEG phase locking values evaluate the effect of electroconvulsive therapy for depressive state Phase locking valueを指標とした経頭蓋磁気刺激誘発脳波（TMS-EEG)による電気痙攣療法前後のうつ状態の評価 Ide Masayuki（井出政行）¹，宮内英里²，太刀川弘和¹，根本清貴¹，新井哲明¹，川崎真弘² ¹Department of Psychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan ²Dept. of Intelligent Interaction Technology, Grad. School of Systems and Information Engineering, Univ. of Tsukuba, Tsukuba, Japan Background: Neuromodulation therapies such as electroconvulsive therapy (ECT) are used to treat several neuropsychiatric disorders, including major depressive disorder (MDD). Recent work has highlighted the use of combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to evaluate the therapeutic effects of neuromodulation; particularly, the phase locking value (PLV) can reportedly assess neuromodulation-induced functional changes in cortical networks. Objective: To examine changes in TMS-induced PLV before and after ECT, and their relationship with depression severity in patients with MDD.Methods: TMS-EEG and the Montgomery-Asberg Depression Rating Scale (MADRS; depression severity) were implemented before and after ECT in 10 patients with MDD. Single-pulse TMS was applied to the visual and motor areas to induce phase propagation in the visuo-motor network at rest. Functional changes were assessed using PLV data.Results: Pre-ECT TMS-induced alpha band (9-12 Hz) PLV was negatively correlated with depression severity, and increments of post-ECT from pre-ECT TMS-induced alpha band PLV were positively correlated with the reduction in depression severity. Conclusions: TMS-EEG-based PLV may be able to assess the therapeutic effects of neuromodulation and depressive states, respectively.		P14-4 Association between response to antidepressants and the increase of CA3 region in left hippocampus with major depressive disorder うつ病患者への抗うつ薬治療は海馬のCornu Ammonis 3領域の増加に関連する Katsuki Asuka（香月あすか）¹，渡邉啓太²，大塚悠加¹，掛田伸吾²，井形亮平¹，興梠征典²，吉村玲児¹ ¹Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan ²Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan. Objective: Recent meta-analysis shows that the volume reductions of hippocampus recover in whom have achieved remission by antidepressants. Although hippocampal function has been shown to be part of a network that contributes to depressive symptoms, it is not elucidated about subfields of hippocampus mechanism are associated with the pathophysiology of major depression. The purpose of the present study is to investigate the association between the improvement of depressive symptoms and volume changes at subfields of hippocampus.Subjects and Methods: Twenty-eight patients with major depressive disorder were enrolled in the present study. They met the DSM-IV-TR criteria for major depressive disorder and their scores on the Hamilton Dating Scale for Depression (HAM-D) were 14 points or more were enrolled the study. All participants underwent T1-weighted structural MRI and were treated with antidepressants for 8 weeks. We defined patients whose scores of HAM-D decreased 50% or more compared to the baseline as responders. We compared the volume of hippocampus including subfields in responders at baseline to the volume at 6 months. The protocol of the study was approved by the Ethics Committee of the University of Occupational and Environmental Health.Results: 1) Nineteen were response to antidepressants, and neithers were recurrence within 6 months. 2) There was no significant difference between the baseline and the 6th month in the whole brain. 3) the total volume of the left hippocampus was significantly increased, 4) and particularly at in the left cornu ammonis (CA) 3 region.Conclusion: There is a possibility that an increase in CA3 region of hippocampus may be related to improve depressive symptoms by the antidepressants.

P14-5 Neuron-Related Blood Inflammatory Markers as an Objective Evaluation Tool for Major Depressive Disorder: An Exploratory Pilot Case-Control Study 神経関連血中炎症物質を用いた客観的うつ病評価：パイロット症例対照研究 Kuwano Nobuki（桑野信貴）¹，加藤隆弘¹，三橋将人²，神庭重信¹ ¹Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ²NanoSomiX, Inc., Irvine, CA, USA Background: Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, human NDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. Methods: As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDD patients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. Results: Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), which suggests that these substances may be contained in the NDE. Thus, we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict the levels of substances per NDE. IL34/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and TNFR1/CD81 were positively correlated with severities of depression and/or various sub-symptoms. Limitations: We did not actually extract NDE from peripheral blood. Conclusions: Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.		P14-6 Wearable devices for evaluation of mood disorders: systematic review and meta-analysis ウェアラブルデバイスの気分障害評価に関する有用性の検討: システマティックレビュー & メタアナリシス Tazawa Yuuki（田澤雄基）¹，和田真孝¹，満倉靖恵²，吉村道隆¹，貝瀬有里子¹，櫛渕澪³，堀込俊朗¹，三村將¹，岸本泰士郎¹ ¹Department of Psychiatry, School of Medicine, Keio University ²Department of System Design Engineering, Faculty of Science and Technology, Keio Universty ³Tokyo Medical and Dental University School of Medicine Background Wearable device has enabled consecutive observation of individual health conditions, and is currently used for various diagnostic and therapeutic purposes in clinical medicine. This study was conducted to validate effectiveness of wearable data for evaluation of conditions in major depressive disorder (MDD) and bipolar disorder patients.MethodsLiterature search was conducted using PubMed/PsycINFO/clinicaltrials.gov until 08/25/17. Studies included used wearable data to compare either patients (MDD and bipolar) and healthy controls, or pre-and post- treatment data from same patient group. Primary outcome were daily activity and sleep-related data from wearable device. Standardized mean difference (SMD) was calculated. ResultsA total of 40 (n=3,926) studies were identified for the analysis. Compared with healthy controls, patients in depressive state had smaller daily activity (SMD=0.949,95%CI=0.528,1.370, p <0.001) and longer wake after sleep onset (SMD=-0.729, 95%CI=-1.203, -0.254, p=0.003). Total sleep time (SMD=-0.356, 95%CI=-0.622,-0.091, p=0.009) and wake after sleep onset (SMD=-0.198, 95%CI=-0.389,-0.006, p=0.043) were longer in euthymic patients compared to healthy controls. In pre- and post- treatment comparison, sleep efficacy (SMD=0.850, 95%CI=0.221,1.479, p<0.001) showed significant improvement after treatment.ConclusionThis meta-analysis indicates that daily activity and sleep data from actigraphy may be useful for evaluation of MDD/bipolar patients. Further investigation and development of algorithm is needed for clinical application.