Oral Session

Oral Session 11 一般口演11

O11-1 Supratherapeutic concentrations of cilostazol inhibits β-amyloid oligomerization in vitro シロスタゾールは抗Aβ-amyloidオリゴマー作用を有する Ono Kenjiro（小野賢二郎）¹，所澤任修¹，小口達敬²，辻まゆみ²，矢野怜¹，木内祐二² ¹Dept. of Neurol., Showa Univ. Sch. of Med. ²Dept. of Pharmacol., Showa Univ. Sch. of Med. Alzheimer disease (AD) is the most common type of dementia, and is currently incurable. The efficacy of existing treatments for AD such as acetylcholinesterase inhibitors is limited to symptom improvement. Research on disease-modifying therapies (DMTs) has conventionally focused on amelioration of CNS pathogenesis. Two neuropathological changes correlate strongly with AD, the appearance of neurofibrillary tangles containing the microtubule-associated protein tau and extracellular amyloid deposits containing amyloid β-protein (Aβ). The aggregation of Aβ is believed to be the key pathogenic event in AD, with oligomeric assemblies thought to be the most neurotoxic form. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for AD patients. The clinical phosphodiesterase type-3 inhibitor cilostazol (CSZ) was recently found to suppress the progression of cognitive decline in patients with stable AD receiving acetylcholinesterase inhibitors. Here we examined the effects of CSZ on in vitro aggregations of Aβ1-40 and Aβ1-42 including oligomerization, using the thioflavin T assay, photo-induced cross-linking of unmodified proteins, and electron microscopy. CSZ inhibited Aβ aggregation, especially oligomer formation. Considering that CSZ might be a key molecule for DMTs of AD, it cannot be ruled out that the low concentration of CSZ achievable in patient dosing may display some ant-oligomeric activity in synergy with its known therapeutic effects.		O11-2 The use of diffusional kurtosis imaging and neurite orientation dispersion and density imaging of the brain in major depressive disorder DKIを用いた大うつ病性障害に伴う大脳形態変化について Ota Miho（太田深秀）^1,2 ¹Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry ²Department of Neuropsychiatry, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) are new diffusional magnetic resonance imaging (dMRI) techniques for the characterization of neural tissues in human brain. In this study, we used these dMRI techniques to evaluate the whole-brain microstructural changes in patients with major depressive disorder (MDD). 23 patients with MDD and 26 healthy subjects underwent dMRI. We compared the dMRI metrics between the 2 groups and examined the relationships between the metrics and the clinical symptoms of MDD. The MDD patients showed significant fractional anisotropy reduction in the bilateral parietal, right parieto-occipital, and right superior temporal corti, compared with the controls. Mean kurtosis values were significantly reduced in MDD patients in the right superior temporal cortex and bilateral posterior thalamic radiation. Neurite density index reductions were found in the right superior temporal cortex, bilateral insulae, right inferior frontal cortex, left parahippocampal region, left middle cerebellar peduncle, and right cerebellum. Regarding the orientation dispersion index (ODI), we detected significant decreases in the left thalamus and left occipital cortex, and significant increases in the bilateral superior longitudinal fasciculi and left posterior thalamic radiation tract. Further, there were significant positive correlations between the total Hamilton Depression Rating scale-21 scores and the ODI values in the right frontal gyri. These results suggest that the DKI and NODDI methods may provide more information about microstructural abnormalities in patients with MDD than the DTI method. It is thus expected that these techniques will be adopted as the informative methods for neuroimaging study.

O11-3 Plasma Phosphoethanolamine as a Biomarker for Major Depressive Disorder うつ病バイオマーカーとしてのリン酸エタノールアミン（PEA） Kawamura Noriyuki（川村則行）¹，ダグラスオセイヒアマン²，大橋由明² ¹Gyoukikai Medical Corporation ²HMT Human Metabolome Technologies, Tsuruoka, Japan ABSTRACTAim: We aimed to develop a simple blood test for detecting major depressive disorder (MDD) using metabolomics approach. Methods:This reserch was perfomed under the permisson of ethical review board. All the psychiatric assessments were performed by Structured Clinical Interview for Diagnosis. In the exploratory cohort, we compared plasma metabolite profiles of 34 MDD patients and 38 non-MDD controls (including 7 adjustment disorder) using capillary electrophoresis-mass spectrometry. Among the candidate metabolites, we focused on a metabolite showing the largest difference. The absolute concentrations were measured in two cohorts from a psychiatric primary care clinic to characterize and check the accuracy of the metabolite biomarker (mBM). Results: Patients with MDD showed significantly low plasma phosphoethanolamine (PEA) levels compared to controls as the best mBM for MDD. An ion-chromatography-fluorescence detection method was developed to measure plasma PEA levels. In the preliminary cohort, we examined 34 MDD and 43 non-MDD subjects. The area under the curve of the receiver operating characteristic (AUC) was 0.92, with sensitivity and specificity greater than88%, at a cut-off of 1.46 μM. In the checking cohort, with 10 MDD and 13 non-MDD subjects, the AUC was 0.89, with sensitivity and specificity of 86% and 100% respectively at a cut-off of 1.48 μM. Plasma PEA inversely correlated with MDD severity, depressed mood, loss of interest, and psychomotor retardation. Conclusion: Plasma PEA is a novel and effective single metabolite biomarker for objective detection of MDD. Use of plasma PEA as a practical and reproducible MDD diagnostic tool would help delineate MDD from other disorders for effective clinical therapeutic decision making.