Faculty Profiles - ALEKSIC Branko

Genetic analysis of early-onset schizophrenia

INVESTIGATION OF RARE SINGLE-NUCLEOTIDE DAB1 VARIANTS AND ITS CONTRIBUTION TO SCHIZOPHRENIA AND AUTISM SPECTRUM DISORDER SUSCEPTIBILITY Reviewed International journal

Nawa, Y; Kimura, H; Ishizuka, K; Kushima, I; Aleksic, B; Ozaki, N

EUROPEAN NEUROPSYCHOPHARMACOLOGY Vol. 29 page： S164 - S165 2019.10

Krgovic, D; Herodez, SS; Senica, N; Kumperscak, HG; Aleksic, B; Nemec, N; Zagorac, A; Vokac, NK

EUROPEAN JOURNAL OF HUMAN GENETICS Vol. 27 page： 1451 - 1452 2019.10

INVESTIGATION OF NOVEL RARE VARIANTS IN NRXN1 CONTRIBUTES TO THE INCREASED RISK OF AUTISM SPECTRUM DISORDERS AND SCHIZOPHRENIA Reviewed International journal

Ishizuka, K; Aleksic, B; Ozaki, N

EUROPEAN NEUROPSYCHOPHARMACOLOGY Vol. 29 page： S829 - S829 2019

TARGET SEQUENCING OF GENES INVOLVED IN NEURODEVELOPMENT FROM WHOLE GENOME COPY NUMBER VARIATION ANALYSIS OF JAPANESE SCHIZOPHRENIA Reviewed International journal

Kimura, H; Aleksic, B; Ishizuka, K; Wang, CY; Kushima, I; Ozaki, N

EUROPEAN NEUROPSYCHOPHARMACOLOGY Vol. 29 page： 1334 - 1334 2019

Assessment of a GLO1 frameshift variant, c.365delC, in Japanese cases of schizophrenia and controls Reviewed International journal

Ishizuka, K; Aleksic, B; Ozaki, N

HUMAN GENOMICS Vol. 12 2018.3

Schizophrenia polygenic risk score and prepubertal developmental impairments Reviewed International journal

Branko Aleksic, Norio Ozaki

The Lancet Psychiatry Vol. 4 ( 1 ) page： 7 - 8 2017.1

Production of four macrocyclic trichothecenes by Stachybotrys chartarum during its development on different building materials as measured by UPLC-MS/MS

Aleksic, B; Bailly, S; Draghi, M; Pestka, JJ; Oswald, IP; Robine, E; Bailly, JD; Lacroix, MZ

BUILDING AND ENVIRONMENT Vol. 106 page： 265 - 273 2016.9

Investigation of the association of rare single nucleotide variants in methyl-CpG-binding domain protein 5 (MBD5) with phenotypes of autism spectrum disorders and schizophrenia. Reviewed International journal

Ishizuka, K; Aleksic, B; Chenyao, W; Kimura, H; Kushima, I; Okada, T; Ozaki, N; Uno, Y

INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY Vol. 19 page： 172 - 173 2016.6

Deep sequencing and association analysis of schizophrenia candidate genes: Focus on glial assembly Reviewed International journal

Aleksic, B; Kimura, H; Xing, JR; Wang, CY; Takasaki, Y; Ishizuka, K; Mori, D; Kushima, I; Oya, T; Nakamura, Y; Yoshimi, A; Ozaki, N

JOURNAL OF PHARMACOLOGICAL SCIENCES Vol. 128 ( 3 ) page： S42 - S42 2015.7

THE POLYMORPHISM OF YWHAE, A GENE ENCODING 14-3-3EPSILON, AND ORBITOFRONTAL SULCOGYRAL PATTERN IN SCHIZOPHRENIA AND HEALTHY SUBJECTS

Suzuki, M; Nakamura, Y; Nakamura, Y; Aleksic, B; Takayanagi, Y; Furuichi, A; Kido, M; Noguchi, K; Kaibuchi, K; Ozaki, N; Takahashi, T

SCHIZOPHRENIA RESEARCH Vol. 153 page： S112 - S112 2014.4

Combination use of two questionnaires for depression screening in the workplace (vol 2, e000596, 2012) Reviewed International journal

Adachi, Y; Branko, A; Nobata, R

BMJ OPEN Vol. 2 ( 3 ) 2012

Genetic analysis of the gene coding for DARPP-32 (PPP1R1B) in Japanese patients with schizophrenia or bipolar disorder

Yoshimi, A; Noda, Y; Yamada, K; Ozaki, N

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN Vol. 128 page： 88 - 88 2008

Analysis of human neuronal cells carrying ASTN2 deletion associated with psychiatric disorders. International journal

Yu Hayashi, Hiroki Okumura, Yuko Arioka, Itaru Kushima, Daisuke Mori, Tzuyao Lo, Gantsooj Otgonbayar, Hidekazu Kato, Yoshihiro Nawa, Hiroki Kimura, Branko Aleksic, Norio Ozaki

Translational psychiatry Vol. 14 ( 1 ) page： 236 - 236 2024.6

Language：English Publishing type：Research paper (scientific journal)

Recent genetic studies have found common genomic risk variants among psychiatric disorders, strongly suggesting the overlaps in their molecular and cellular mechanism. Our research group identified the variant in ASTN2 as one of the candidate risk factors across these psychiatric disorders by whole-genome copy number variation analysis. However, the alterations in the human neuronal cells resulting from ASTN2 variants identified in patients remain unknown. To address this, we used patient-derived and genome-edited iPS cells with ASTN2 deletion; cells were further differentiated into neuronal cells. A comprehensive gene expression analysis using genome-edited iPS cells with variants on both alleles revealed that the expression level of ZNF558, a gene specifically expressed in human forebrain neural progenitor cells, was greatly reduced in ASTN2-deleted neuronal cells. Furthermore, the expression of the mitophagy-related gene SPATA18, which is repressed by ZNF558, and mitophagy activity were increased in ASTN2-deleted neuronal cells. These phenotypes were also detected in neuronal cells differentiated from patient-derived iPS cells with heterozygous ASTN2 deletion. Our results suggest that ASTN2 deletion is related to the common pathogenic mechanism of psychiatric disorders by regulating mitophagy via ZNF558.

DOI： 10.1038/s41398-024-02962-4

Study of the genetic association between selected 3q29 region genes and schizophrenia and autism spectrum disorder in the Japanese population.

Gantsooj Otgonbayar, Tzuyao Lo, Yu Hayashi, Sho Furuta, Branko Aleksic, Yoshihiro Nawa, Itaru Kushima, Hidekazu Kato, Hiroki Kimura, Norio Ozaki

Nagoya journal of medical science Vol. 86 ( 2 ) page： 216 - 222 2024.5

Language：English Publishing type：Research paper (scientific journal)

Psychiatric disorders are highly inheritable, and most psychiatric disorders exhibit genetic overlap. Recent studies associated the 3q29 recurrent deletion with schizophrenia (SCZ) and autism spectrum disorder (ASD). In this study, we investigated the association of genes in the 3q29 region with SCZ and ASD. TM4SF19 and PAK2 were chosen as candidate genes for this study based on evidence from previous research. We sequenced TM4SF19 and PAK2 in 437 SCZ cases, 187 ASD cases and 524 controls in the Japanese population. Through targeted sequencing, we identified 6 missense variants among the cases (ASD & SCZ), 3 missense variants among controls, and 1 variant common to both cases and controls; however, no loss-of-function variants were identified. Fisher's exact test showed a significant association of variants in TM4SF19 among cases (p=0.0160). These results suggest TM4SF19 variants affect the etiology of SCZ and ASD in the Japanese population. Further research examining 3q29 region genes and their association with SCZ and ASD is thus needed.

DOI： 10.18999/nagjms.86.2.216

Psychiatric Lecture 成因・危険因子ゲノムコピー数バリアントに着目した重症摂食症の病因解析

久島周, 今枝美穂, 田中聡, 加藤秀一, 大矢友子, 中杤昌弘, アレクシッチ・ブランコ, 尾崎紀夫

精神科臨床Legato Vol. 10 ( 1 ) page： 18 - 21 2024.4

Language：Japanese Publisher：(株)メディカルレビュー社

摂食症の発症には遺伝的要因が関与することが知られている。筆者らは,重症の摂食症患者を対象にゲノムコピー数バリアント(CNV)解析を行った結果,神経発達症に関連するCNVが発症リスクに関与すること,摂食症病態にシナプス機能異常が寄与することが示唆された。この知見に基づき,今後,分子メカニズムの解明が進むことが期待される。(著者抄録)

Phenotypes for general behavior, activity, and body temperature in 3q29 deletion model mice. International journal

Daisuke Mori, Ryosuke Ikeda, Masahito Sawahata, Sho Yamaguchi, Akiko Kodama, Takashi Hirao, Yuko Arioka, Hiroki Okumura, Chihiro Inami, Toshiaki Suzuki, Yu Hayashi, Hidekazu Kato, Yoshihiro Nawa, Seiko Miyata, Hiroki Kimura, Itaru Kushima, Branko Aleksic, Hiroyuki Mizoguchi, Taku Nagai, Takanobu Nakazawa, Ryota Hashimoto, Kozo Kaibuchi, Kazuhiko Kume, Kiyofumi Yamada, Norio Ozaki

Translational psychiatry Vol. 14 ( 1 ) page： 138 - 138 2024.3

Language：English Publishing type：Research paper (scientific journal)

Whole genome analysis has identified rare copy number variations (CNV) that are strongly involved in the pathogenesis of psychiatric disorders, and 3q29 deletion has been found to have the largest effect size. The 3q29 deletion mice model (3q29-del mice) has been established as a good pathological model for schizophrenia based on phenotypic analysis; however, circadian rhythm and sleep, which are also closely related to neuropsychiatric disorders, have not been investigated. In this study, our aims were to reevaluate the pathogenesis of 3q29-del by recreating model mice and analyzing their behavior and to identify novel new insights into the temporal activity and temperature fluctuations of the mouse model using a recently developed small implantable accelerometer chip, Nano-tag. We generated 3q29-del mice using genome editing technology and reevaluated common behavioral phenotypes. We next implanted Nano-tag in the abdominal cavity of mice for continuous measurements of long-time activity and body temperature. Our model mice exhibited weight loss similar to that of other mice reported previously. A general behavioral battery test in the model mice revealed phenotypes similar to those observed in mouse models of schizophrenia, including increased rearing frequency. Intraperitoneal implantation of Nano-tag, a miniature acceleration sensor, resulted in hypersensitive and rapid increases in the activity and body temperature of 3q29-del mice upon switching to lights-off condition. Similar to the 3q29-del mice reported previously, these mice are a promising model animals for schizophrenia. Successive quantitative analysis may provide results that could help in treating sleep disorders closely associated with neuropsychiatric disorders.

DOI： 10.1038/s41398-023-02679-w