研究者詳細 - アレクシッチ　ブランコ

論文 - アレクシッチ　ブランコ

分割表示 255 件中 101 - 120 件目／全件表示 >>

Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia.

Ishizuka K, Yoshida T, Kawabata T, Imai A, Mori H, Kimura H, Inada T, Okahisa Y, Egawa J, Usami M, Kushima I, Morikawa M, Okada T, Ikeda M, Branko A, Mori D, Someya T, Iwata N, Ozaki N

Journal of neurodevelopmental disorders 12 巻 ( 1 ) 頁： 25 2020年12月

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder (vol 53, pg 891, 2017) 国際誌

Lim, ET; Uddin, M; De Rubeis, S; Chan, YL; Kamumbu, AS; Zhang, XC; D'Gama, AM; Kim, SN; Hill, RS; Goldberg, AP; Poultney, C; Minshew, NJ; Kushima, I; Aleksic, B; Ozaki, N; Parellada, M; Arango, C; Penzol, MJ; Carracedo, A; Kolevzon, A; Hultman, CM; Weiss, LA; Fromer, M; Chiocchetti, AG; Freitag, CM; Church, GM; Scherer, SW; Buxbaum, JD; Walsh, CA

NATURE NEUROSCIENCE 23 巻 ( 9 ) 頁： 1176 - 1176 2020年9月

ヒストンメチル化修飾関連遺伝子KDM4Cにおける稀なゲノムコピー数変異と統合失調症および自閉スペクトラム症との関連

加藤秀一, 久島周, 森大輔, 有岡祐子, 石塚佳奈子, 木村大樹, ブランコ・アレクシッチ, 尾崎紀夫

日本神経精神薬理学会年会・日本生物学的精神医学会年会・日本精神薬学会総会・学術集会合同年会プログラム・抄録集 50回・42回・4回巻頁： 217 - 217 2020年8月

ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk 査読有り国際誌

Sekiguchi, M; Sobue, A; Kushima, I; Wang, CY; Arioka, Y; Kato, H; Kodama, A; Kubo, H; Ito, N; Sawahata, M; Hada, K; Ikeda, R; Shinno, M; Mizukoshi, C; Tsujimura, K; Yoshimi, A; Ishizuka, K; Takasaki, Y; Kimura, H; Xing, JR; Yu, YJ; Yamamoto, M; Okada, T; Shishido, E; Inada, T; Nakatochi, M; Takano, T; Kuroda, K; Amano, M; Aleksic, B; Yamomoto, T; Sakuma, T; Aida, T; Tanaka, K; Hashimoto, R; Arai, M; Ikeda, M; Iwata, N; Shimamura, T; Nagai, T; Nabeshima, T; Kaibuchi, K; Yamada, K; Mori, D; Ozaki, N

TRANSLATIONAL PSYCHIATRY 10 巻 ( 1 ) 頁： 247 - 247 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Translational Psychiatry

Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.

DOI： 10.1038/s41398-020-00917-z

その他リンク： http://www.nature.com/articles/s41398-020-00917-z

A recurrentPJA1variant in trigonocephaly and neurodevelopmental disorders 国際誌

Suzuki, T; Suzuki, T; Raveau, M; Miyake, N; Sudo, G; Tsurusaki, Y; Watanabe, T; Sugaya, Y; Tatsukawa, T; Mazaki, E; Shimohata, A; Kushima, I; Aleksic, B; Shiino, T; Toyota, T; Iwayama, Y; Nakaoka, K; Ohmori, I; Sasaki, A; Watanabe, K; Hirose, S; Kaneko, S; Inoue, Y; Yoshikawa, T; Ozaki, N; Kano, M; Shimoji, T; Matsumoto, N; Yamakawa, K

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY 7 巻 ( 7 ) 頁： 1117 - 1131 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Neurodevelopmental disorders (NDDs) often associate with epilepsy or craniofacial malformations. Recent large‐scale DNA analyses identified hundreds of candidate genes for NDDs, but a large portion of the cases still remain unexplained. We aimed to identify novel candidate genes for NDDs.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We performed exome sequencing of 95 patients with NDDs including 51 with trigonocephaly and subsequent targeted sequencing of additional 463 NDD patients, functional analyses of variant <jats:italic>in vitro,</jats:italic> and evaluations of autism spectrum disorder (ASD)‐like phenotypes and seizure‐related phenotypes <jats:italic>in vivo</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We identified <jats:italic>de novo</jats:italic> truncation variants in nine novel genes; <jats:italic>CYP1A1</jats:italic>, <jats:italic>C14orf119</jats:italic>, <jats:italic>FLI1</jats:italic>, <jats:italic>CYB5R4</jats:italic>, <jats:italic>SEL1L2, RAB11FIP2, ZMYND8, ZNF143,</jats:italic> and <jats:italic>MSX2. MSX2</jats:italic> variants have been described in patients with cranial malformations, and our present patient with the <jats:italic>MSX2 de novo</jats:italic> truncation variant showed cranial meningocele and partial epilepsy. MSX2 protein is known to be ubiquitinated by an E3 ubiquitin ligase PJA1, and interestingly we found a <jats:italic>PJA1</jats:italic> hemizygous p.Arg376Cys variant recurrently in seven Japanese NDD patients; five with trigonocephaly and one with partial epilepsy, and the variant was absent in 886 Japanese control individuals. <jats:italic>Pja1</jats:italic> knock‐in mice carrying p.Arg365Cys, which is equivalent to p.Arg376Cys in human, showed a significant decrease in PJA1 protein amount, suggesting a loss‐of‐function effect of the variant. <jats:italic>Pja1</jats:italic> knockout mice displayed moderate deficits in isolation‐induced ultrasonic vocalizations and increased seizure susceptibility to pentylenetetrazole.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>These findings propose novel candidate genes including <jats:italic>PJA1</jats:italic> and <jats:italic>MSX2</jats:italic> for NDDs associated with craniofacial abnormalities and/or epilepsy.</jats:p></jats:sec>

DOI： 10.1002/acn3.51093

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/acn3.51093

Validation and factor structure of the Japanese version of the inventory to diagnose depression, lifetime version for pregnant women 国際誌

Kubota, C; Inada, T; Nakamura, Y; Shiino, T; Ando, M; Aleksic, B; Yamauchi, A; Morikawa, M; Okada, T; Ohara, M; Sato, M; Murase, S; Goto, S; Kanai, A; Ozaki, N

PLOS ONE 15 巻 ( 6 ) 頁： e0234240 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PLoS ONE

Introduction A history of major depressive disorder before pregnancy is one risk factor for peripartum depression. Therefore, the purpose of the present study was to examine the validation and factor structure of the Japanese version of the Inventory to Diagnose Depression, Lifetime version (IDDL) for pregnant women. Methods The study participants were 556 pregnant women. Factor analysis was performed to identify the factor structure, construct validity was examined based on the results of the factor analysis, and reliability was examined using Cronbach's α coefficient. Results Based on the results of the factor analysis of the IDDL, a bifactor model composed of a single general dimension along with the following five factors was extracted: (1) depression, anxiety, and irritability (items 1, 2, 8-10, and 19-21); (2) retardation, decreased concentration, indecisiveness, and insomnia (items 4, 11, 12, and 17); (3) decrease in appetite/significant weight loss (items 13 and 14); (4) increase in appetite/significant weight gain (items 15 and 16); and (5) diminished interest, pleasure, and libido (items 5-7). Cronbach's α coefficients for these five factors were as follows: 0.910, 0.815, 0.780, 0.683, and 0.803, respectively. Conclusions The reliability, construct validity, and factor structure of the Japanese version of the IDDL were confirmed in pregnant women.

DOI： 10.1371/journal.pone.0234240

The Risk Factors Predicting Suicidal Ideation Among Perinatal Women in Japan 国際誌

Kubota, C; Inada, T; Shiino, T; Ando, M; Sato, M; Nakamura, Y; Yamauchi, A; Morikawa, M; Okada, T; Ohara, M; Aleksic, B; Murase, S; Goto, S; Kanai, A; Ozaki, N

FRONTIERS IN PSYCHIATRY 11 巻頁： 441 - 441 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Psychiatry

Introduction: The aim of the present study was to elucidate the foreseeable risk factors for suicidal ideation among Japanese perinatal women. Methods: This cohort study was conducted in Nagoya, Japan, from July 2012 to March 2018. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was conducted at four time points: early pregnancy, late pregnancy, 5 days postpartum, and 1 month postpartum. A total of 430 women completed the questionnaires. A logistic regression analysis was performed using the presence of suicidal ideation on the EPDS as an objective variable. The explanatory variables were age, presence of physical or mental disease, smoking and drinking habits, education, hospital types, EPDS total score in early pregnancy, bonding, and quality and amount of social support, as well as the history of major depressive disorder (MDD). Results: The rate of participants who were suspected of having suicidal ideation at any of the four time points was 11.6% (n=52), with the highest (n=25, 5.8%) at late pregnancy. For suicidal ideation, education level (OR: 1.19; 95% CI: 1.00–1.41; p=0.047), EPDS total points in the pregnancy period (OR: 1.25; 95% CI: 1.16–1.34; p < 0.000), a history of MDD (OR: 2.16; 95% CI: 1.00–4.79; p=0.049), and presence of mental disease (OR: 2.39; 95% CI: 1.00–5.70; p=0.049) were found to be risk factors for suicidal ideation. Age [odds ratio (OR): 0.88; 95% confidence interval (CI): 0.80–0.95; p=.002] and quality of social support (OR: 0.77; 95% CI: 0.60–0.99; p=.041) were found to be protective factors. Conclusion: Based on these results, effective preventive interventions, such as increasing the quality of social support and confirming the history of depression, should be carried out in pregnant depressive women at the early stage of the perinatal period.

DOI： 10.3389/fpsyt.2020.00441

Generation and analysis of novel Reln-deleted mouse model corresponding to exonic Reln deletion in schizophrenia 国際誌

Sawahata, M; Mori, D; Arioka, Y; Kubo, H; Kushima, I; Kitagawa, K; Sobue, A; Shishido, E; Sekiguchi, M; Kodama, A; Ikeda, R; Aleksic, B; Kimura, H; Ishizuka, K; Nagai, T; Kaibuchi, K; Nabeshima, T; Yamada, K; Ozaki, N

PSYCHIATRY AND CLINICAL NEUROSCIENCES 74 巻 ( 5 ) 頁： 318 - 327 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

<jats:sec><jats:title>Aim</jats:title><jats:p>A Japanese individual with schizophrenia harboring a novel exonic deletion in <jats:italic>RELN</jats:italic> was recently identified by genome‐wide copy‐number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether <jats:italic>Reln</jats:italic> deficiency is associated with the pathogenesis of schizophrenia.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A mouse line with a novel <jats:italic>RELN</jats:italic> exonic deletion (<jats:italic>Reln</jats:italic>‐del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The phenotype of homozygous <jats:italic>Reln</jats:italic>‐del mice was similar to that of <jats:italic>reeler</jats:italic> mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous <jats:italic>Reln</jats:italic>‐del mice was approximately half of that in wild‐type mice. Conversely, behavioral analyses in heterozygous <jats:italic>Reln</jats:italic>‐del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three‐chamber social interaction test. <jats:italic>In vitro</jats:italic> reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous <jats:italic>Reln</jats:italic>‐del mice.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The present results in novel <jats:italic>Reln</jats:italic>‐del mice modeled after our patient with a novel exonic deletion in <jats:italic>RELN</jats:italic> are expected to contribute to the development of reelin‐based therapies for schizophrenia.</jats:p></jats:sec>

DOI： 10.1111/pcn.12993

Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis 国際誌

Yu, YJ; Chaulagain, A; Pedersen, SA; Lydersen, S; Leventhal, BL; Szatmari, P; Aleksic, B; Ozaki, N; Skokauskas, N

BMC PSYCHIATRY 20 巻 ( 1 ) 頁： 121 - 121 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMC Psychiatry

Background: This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD). Method: We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660). Results: We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials-involving 552 patients in total-were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P = 0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P = 0.68). There was no evidence of publication bias. Conclusion: This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed. Trial registration: The study protocol is registered in PROSPERO (Reference number: CRD42018092660).

DOI： 10.1186/s12888-020-2477-9

Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism

Satterstrom, FK; Kosmicki, JA; Wang, JB; Breen, MS; De Rubeis, S; An, JY; Peng, MS; Collins, R; Grove, J; Klei, L; Stevens, C; Reichert, J; Mulhern, MS; Artomov, M; Gerges, S; Sheppard, B; Xu, XY; Bhaduri, A; Norman, U; Brand, H; Schwartz, G; Nguyen, R; Guerrero, EE; Dias, C; Betancur, C; Cook, EH; Gallagher, L; Gill, M; Sutcliffe, JS; Thurm, A; Zwick, ME; Borglum, AD; State, MW; Cicek, AE; Talkowski, ME; Cutler, DJ; Devlin, B; Sanders, SJ; Roeder, K; Daly, MJ; Buxbaum, JD; Aleksic, B; Anney, R; Barbosa, M; Bishop, S; Brusco, A; Bybjerg-Grauholm, J; Carracedo, A; Chan, MCY; Chiocchetti, AG; Chung, BHY; Coon, H; Cuccaro, ML; Curró, A; Dalla Bernardina, B; Doan, R; Domenici, E; Dong, S; Fallerini, C; Fernández-Prieto, M; Ferrero, GB; Freitag, CM; Fromer, M; Gargus, JJ; Geschwind, D; Giorgio, E; González-Peñas, J; Guter, S; Halpern, D; Hansen-Kiss, E; He, X; Herman, GE; Hertz-Picciotto, I; Hougaard, DM; Hultman, CM; Ionita-Laza, I; Jacob, S; Jamison, J; Jugessur, A; Kaartinen, M; Knudsen, GP; Kolevzon, A; Kushima, I; Lee, SL; Lehtimäki, T; Lim, ET; Lintas, C; Lipkin, WI; Lopergolo, D; Lopes, F; Ludena, Y; Maciel, P; Magnus, P; Mahjani, B; Maltman, N; Manoach, DS; Meiri, G; Menashe, I; Miller, J; Minshew, N; Montenegro, EMS; Moreira, D; Morrow, EM; Mors, O; Mortensen, PB; Mosconi, M; Muglia, P; Neale, BM; Nordentoft, M; Ozaki, N; Palotie, A; Parellada, M; Passos-Bueno, MR; Pericak-Vance, M; Persico, AM; Pessah, I; Puura, K; Reichenberg, A; Renieri, A; Riberi, E; Robinson, EB; Samocha, KE; Sandin, S; Santangelo, SL; Schellenberg, G; Scherer, SW; Schlitt, S; Schmidt, R; Schmitt, L; Silva, IMW; Singh, T; Siper, PM; Smith, M; Soares, G; Stoltenberg, C; Suren, P; Susser, E; Sweeney, J; Szatmari, P; Tang, L; Tassone, F; Teufel, K; Trabetti, E; Trelles, MD; Walsh, CA; Weiss, LA; Werge, T; Werling, DM; Wigdor, EM; Wilkinson, E; Willsey, AJ; Yu, TW; Yu, MH; Yuen, R; Zachi, E; Agerbo, E; Als, TD; Appadurai, V; Baekvad-Hansen, M; Belliveau, R; Buil, A; Carey, CE; Cerrato, F; Chambert, K; Churchhouse, C; Dalsgaard, S; Demontis, D; Dumont, A; Goldstein, J; Hansen, CS; Hauberg, ME; Hollegaard, MV; Howrigan, DP; Huang, HL; Maller, J; Martin, AR; Martin, J; Mattheisen, M; Moran, J; Pallesen, J; Palmer, DS; Pedersen, CB; Pedersen, MG; Poterba, T; Poulsen, JB; Ripke, S; Schork, AJ; Thompson, WK; Turley, P; Walters, RK

CELL 180 巻 ( 3 ) 頁： 568 - + 2020年2月

Characterization of a schizophrenia patient with a rare RELN deletion by combining genomic and patient-derived cell analyses 査読有り国際誌

Arioka, Y; Hirata, A; Kushima, I; Aleksic, B; Mori, D; Ozaki, N

SCHIZOPHRENIA RESEARCH 216 巻頁： 511 - 515 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Schizophrenia Research

Genetic studies have identified rare RELN variants as risk factors for psychiatric disorders. However, additional genetic factors appear to be necessary for disease onset. Detailed genetic information and the use of patient-derived neuronal cells may thus enable to discover these disease-related additional factors. Here, we performed whole-genome sequencing of a schizophrenia patient with a rare RELN deletion and his healthy mother, and examined the phenotypes of 3D-cultured neuronal cells derived from induced pluripotent stem cells of this patient. Our results revealed that, along with the RELN deletion, neuronal death was promoted in this patient; thus, neuronal death may be a vulnerable factor for schizophrenia.

DOI： 10.1016/j.schres.2019.10.038

Drug-Induced Extrapyramidal Symptoms Scale of the Norwegian version: inter-rater and test-retest reliability 国際誌

Weidle, B; Chaulagain, A; Stensen, K; Aleksic, B; Skokauskas, N; Inada, T

NORDIC JOURNAL OF PSYCHIATRY 73 巻 ( 8 ) 頁： 546 - 550 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Informa UK Limited

Background: The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) is a multidimensional rating scale designed for the fast, easy and reliable assessment of extrapyramidal symptoms (EPSs) induced by antipsychotics. Aim: The aim of this study was to validate the level of inter-rater and test–retest reliability of the Norwegian translation of this scale. Methods: A total of 125 video clips showing a variety of or no signs of EPSs were used in the present study. The participants recorded were Japanese psychiatric patients receiving first- and/or second-generation antipsychotics. A total of 103 patients (47 males and 56 females), diagnosed with schizophrenia (n = 68) or mood disorders (n = 35) appeared in the video clips. Their mean age was 48.7 ± 16.3 years (range 18–80) at the time of video recording. Inter-rater agreement was assessed with five raters and test–retest reliability with three. Results: Inter-rater reliability analyses showed interclass correlation coefficients (ICCs) ranging from 0.74 to 0.93 for each individual item. Test–retest reliability analysed independently for each rater ranged from 0.71 to 0.96. Conclusions: Inter-rater and test–retest agreement exhibited satisfactory ICC levels above 0.70. The Norwegian version of the DIEPSS is a reliable instrument for the assessment of drug-induced EPSs.

DOI： 10.1080/08039488.2019.1665708

Relation Between Perinatal Depressive Symptoms, Harm Avoidance, and a History of Major Depressive Disorder: A Cohort Study of Pregnant Women in Japan 査読有り国際誌

Kubota, C; Inada, T; Shiino, T; Ando, M; Aleksic, B; Yamauchi, A; Sato, M; Ohara, M; Murase, S; Morikawa, M; Nakamura, Y; Okada, T; Goto, S; Kanai, A; Ozaki, N

FRONTIERS IN PSYCHIATRY 10 巻頁： 515 - 515 2019年7月

Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect 国際誌

Ikeda, M; Takahashi, A; Kamatanim, Y; Momozawa, Y; Saito, T; Kondo, K; Shimasaki, A; Kawase, K; Sakusabe, T; Iwayama, Y; Toyota, T; Wakudas, T; Kikuchi, M; Kanahara, N; Yamamori, H; Yasuda, Y; Watanabe, Y; Hoya, S; Aleksic, B; Kushima, I; Arai, H; Takaki, M; Hattori, K; Kurrugi, H; Okahisa, Y; Ohnuma, T; Ozaki, N; Someya, T; Hashimotovs, R; Yoshikawa, T; Kubo, M; Iwata, N

SCHIZOPHRENIA BULLETIN 45 巻 ( 4 ) 頁： 824 - 834 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Oxford University Press (OUP)

Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS] and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54 479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (Pbest = 4.1 × 10−10), SLC38A3 (Pbest = 5.7 × 10−10), and CABP1-ACADS (Pbest = 9.8 × 10−9). Subsequent meta-analysis between our samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and another study detected 12 additional susceptibility loci. Polygenic risk score (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest = 4.0 × 10−11) and between SCZ and BD in the JPN population (P ~ 10−40); however, a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD within/across populations. Genetic correlation analysis supported the PRS results; the genetic correlation between JPN-SCZ and PGC-SCZ was ρ = 0.58, whereas a similar/ lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, ρ = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible susceptibility genes for SCZ and (b) SCZ “risk” effect is shared with other psychiatric disorders even across populations.

DOI： 10.1093/schbul/sby140

Methylation analysis for postpartum depression: a case control study 査読有り国際誌

Nakamura, Y; Nakatochi, M; Kunimoto, S; Okada, T; Aleksic, B; Toyama, M; Shiino, T; Morikawa, M; Yamauchi, A; Yoshimi, A; Furukawa-Hibi, Y; Nagai, T; Ohara, M; Kubota, C; Yamada, K; Ando, M; Ozaki, N

BMC PSYCHIATRY 19 巻 ( 1 ) 頁： 190 - 190 2019年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BMC Psychiatry

Background: Postpartum depression (PPD) is a major depressive disorder that occurs after childbirth. Objective diagnostic and predictive methods for PPD are important for early detection and appropriate intervention. DNA methylation has been recognized as a potential biomarker for major depressive disorder. In this study, we used methylation analysis and peripheral blood to search for biomarkers that could to lead to the development a predictive method for PPD. Methods: Study participants included 36 pregnant women (18 cases and 18 controls determined after childbirth). Genome-wide DNA methylation profiles were obtained by analysis with an Infinium Human Methylation 450BeadChip. The association of DNA methylation status at each DNA methylation site with PPD was assessed using linear regression analysis. We also conducted functional enrichment analysis of PPD using The Database for Annotation, Visualization and Integrated Discovery 6.8 to explore enriched functional-related gene groups for PPD. Results: In the analysis with postpartum depressed state as an independent variable, the difference in methylation frequency between the postpartum non-depressed group and the postpartum depressed group was small, and sites with genome-wide significant differences were not confirmed. After analysis by The Database for Annotation, Visualization and Integrated Discovery 6.8, we revealed four gene ontology terms, including axon guidance, related to postpartum depression. Conclusions: These findings may help with the development of an objective predictive method for PPD.

DOI： 10.1186/s12888-019-2172-x

Effects of Snoezelen-Multisensory environment on CARS scale in adolescents and adults with autism spectrum disorder 査読有り国際誌

Novakovic, N; Milovancevic, MP; Dejanovic, SD; Aleksic, B

RESEARCH IN DEVELOPMENTAL DISABILITIES 89 巻頁： 51 - 58 2019年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Research in Developmental Disabilities

Background: New classification system Diagnostic and statistical manual of mental disorders. 5th ed.(DSM – 5) includes sensory problems as one of the symptoms in diagnostic profile of Autism Spectrum Disorder (ASD). Researching the effects of sensory integration treatment may improve new approaches to the individuals with ASD. The objective of this study is to determine the effects of Snoezelen, multisensory environment on the severity of ASD and stereotyped/repetitive behaviours in adolescents and adults using CARS scale. Method: The study involved 40 subjects with ASD associated with intellectual difficulties of both sexes, aged 15–35. The subjects were randomly divided into two groups: a control one (without treatment) and an experimental one (with treatment). The assessments were rated by CARS (Childhood Autism Rating Scale) before and after the three-month treatment. Results: In the experimental group, there was a statistically significant difference of the total CARS score before and after the treatment (p < 0.0005). Comparing the results of both experimental and control groups, a statistically significant difference was found on total CARS score (p < 0.0005). Conslusion: The results in the present study indicate that the continual sessions in Snoezelen room had effects on reducing severity of ASD and repetitive and stereotyped behaviours on CARS scale.

DOI： 10.1016/j.ridd.2019.03.007

統合失調症と自閉スペクトラム症におけるDAB1遺伝子内の稀な一塩基変異の探索

名和佳弘, 木村大樹, 石塚佳奈子, 久島周, アレクシッチ・ブランコ, 尾崎紀夫

精神神経学雑誌 ( 2019特別号 ) 頁： S759 - S759 2019年6月

KDM4C遺伝子における稀なバリアントと統合失調症および自閉スペクトラム症との関連

加藤秀一, 石塚佳奈子, 木村大樹, 久島周, アレクシッチ・ブランコ, 尾崎紀夫

精神神経学雑誌 ( 2019特別号 ) 頁： S614 - S614 2019年6月

Proteomic analysis of lymphoblastoid cell lines from schizophrenic patients (vol 9, 126, 2019) 査読有り国際誌

Yoshimi, A; Yamada, S; Kunimoto, S; Aleksic, B; Hirakawa, A; Ohashi, M; Matsumoto, Y; Hada, K; Itoh, N; Arioka, Y; Kimura, H; Kushima, I; Nakamura, Y; Shiino, T; Mori, D; Tanaka, S; Hamada, S; Noda, Y; Nagai, T; Yamada, K; Ozaki, N

TRANSLATIONAL PSYCHIATRY 9 巻 ( 1 ) 頁： 146 - 146 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Translational Psychiatry

The original Article required a few updates; one co-author name, which was given as Hiroki Kiumura, has been updated to Hiroki Kimura. Furthermore, supplementary information has been updated, and grant numbers have been added. These updates have been made to both the PDF and HTML versions of this Article.

DOI： 10.1038/s41398-019-0479-5

Joint Degree Program for Graduate Students at the Nagoya University Graduate School of Medicine 査読有り

Kasuya, H; Aleksic, B; Sumigama, S; Bustos, I; Hasegawa, H; Kasai, MP; Kobayashi, M; Samizo, Y

NAGOYA JOURNAL OF MEDICAL SCIENCE 81 巻 ( 2 ) 頁： 183 - 192 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nagoya journal of medical science

In a world of increasing academic mobility, most universities seek to give their students opportunities to experience education in different countries, which is especially true for senior research students. The Nagoya University Graduate School of Medicine started a joint degree program (JDP) for PhD students with the University of Adelaide, Faculty of Health Science (Australia) in 2015 and with Lund University Faculty of Medicine (Sweden) in 2017. Furthermore, we have started a new JDP with the University of Freiburg, Faculty of Medicine (Germany) in 2018. This article reports the issues specific to counterpart medical schools, including student's recruitment, the curriculum, and the general differences between each schools. JDPs are not only important for educational collaboration, but also as a strategy to encourage international research collaboration, which is a core criterion to a university's world-ranking reputation. Acquiring knowledge about educational strategies that are implemented in different foreign medical schools represents a unique opportunity to improve our own curriculum.

DOI： 10.18999/nagjms.81.2.183

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論文 - アレクシッチ ブランコ

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論文 - アレクシッチ　ブランコ