Relationship between changes in amino acid metabolism during pregnancy and postpartum depression.

• Project/Area Number: 18K19761
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Fujita Health University
• Principal Investigator: Saito Kuniaki 藤田医科大学, 保健学研究科, 教授 (80262765)
• Co-Investigator(Kenkyū-buntansha): 山本 康子 藤田医科大学, 保健学研究科, 准教授 (00331869) ; 藤垣 英嗣 藤田医科大学, 保健学研究科, 講師 (00612631) ; 毛利 彰宏 藤田医科大学, 保健学研究科, 准教授 (20597851) ; 星 雅人 藤田医科大学, 保健学研究科, 講師 (40633996)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 周産期うつ病 / アミノ酸代謝 / トリプトファン代謝 / 産後うつ病 / 周産期うつ / 周産期栄養状態 / 出生時体重

Outline of Final Research Achievements

Postpartum depression is a common disorder that occurs in approximately 5%-10% of pregnant women and has a negative impact not only on the affected mother but also on the child. This study aimed to establish molecular markers that allow detection of postpartum depression by performing metabolome analysis on prenatal and postnatal serum samples from perinatal pregnant subjects.
According to the Edinburgh postnatal depression scale, the subjects were divided into a nondepressive (ND) group, a postpartum depressive (PD) group, and a continuous depressive (CD) group.Principal component analysis revealed that the amino acid pattern in the PD group was different from that in the ND group. However, the PD group showed a pattern similar to that of the CD group. In the PD group, a correlation was found between the postpartum depression score and glutamic acid.These results demonstrate that the onset of postpartum depression may be predicted by examining the amino acid profile before childbirth.

Academic Significance and Societal Importance of the Research Achievements

本検討により産前のトリプトファン代謝やアミノ酸プロファイルを検討する事で、産後の抑うつ病態の発症が予測できる可能性が示唆されたことから、広く臨床に貢献できる検討であると考えられる。

Research Products

• [Int'l Joint Research] Kangwon National University(韓国)
• [Int'l Joint Research] Husanuddin University(インドネシア)
• [Int'l Joint Research] Kangwon National University(韓国)
• [Journal Article] Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid (2021)
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  • Journal Title: Behavioural Brain Research Volume: 405 Pages: 113191-113191
  • DOI: 10.1016/j.bbr.2021.113191
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• [Journal Article] Progranulin depletion inhibits proliferation via the transforming growth factor beta/SMAD family member 2 signaling axis in Kasumi-1 cells (2021)
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  • Journal Title: Heliyon Volume: 7 Issue: 1 Pages: e05849-e05849
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• [Journal Article] Serum metabolic profiles of the tryptophan-kynurenine pathway in the high risk subjects of major depressive disorder (2020)
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  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 1961-1961
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• [Journal Article] Kynurenine produced by indoleamine 2,3-dioxygenase 2 exacerbates acute liver injury by carbon tetrachloride in mice. (2020)
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• [Journal Article] Kynurenine plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced colitis in mice. (2020)
  • Author(s): Tashita C, Hoshi M, Hirata A, Nakamoto K, Ando T, Hattori T, Yamamoto Y, Tezuka H, Tomita H, Hara A, Saito K.
  • Journal Title: World J Gastroenterol. Volume: 26 Issue: 9 Pages: 918-932
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• [Journal Article] Lithium attenuates d‐amphetamine‐induced hyperlocomotor activity in mice via inhibition of interaction between cyclooxygenase‐2 and indoleamine‐2,3‐dioxygenase (2020)
  • Author(s): Phan Dieu‐Hien、Shin Eun‐Joo、Jeong Ji Hoon、Tran Hai‐Quyen、Sharma Naveen、Nguyen Bao Trong、Jung Tae Woo、Nah Seung‐Yeol、Saito Kuniaki、Nabeshima Toshitaka、Kim Hyoung‐Chun
  • Journal Title: Clinical and Experimental Pharmacology and Physiology Volume: 47 Issue: 5 Pages: 790-797
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• [Journal Article] Indoleamine-2,3-dioxygenase-1 is a molecular target for the protective activity of mood stabilizers against mania-like behavior induced by d-amphetamine (2020)
  • Author(s): Tran Hai-Quyen、Shin Eun-Joo、Saito Kuniaki、Tran The-Vinh、Phan Dieu-Hien、Sharma Naveen、Kim Dae-Won、Choi Soo Young、Jeong Ji Hoon、Jang Choon-Gon、Cheong Jae Hoon、Nabeshima Toshitaka、Kim Hyoung-Chun
  • Journal Title: Food and Chemical Toxicology Volume: 136 Pages: 110986-110986
  • DOI: 10.1016/j.fct.2019.110986
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• [Journal Article] Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker. (2019)
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• [Journal Article] Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma (2019)
  • Author(s): Yamasuge Wakana、Yamamoto Yasuko、Fujigaki Hidetsugu、Hoshi Masato、Nakamoto Kentaro、Kunisawa Kazuo、Mouri Akihiro、Nabeshima Toshitaka、Saito Kuniaki
  • Journal Title: Cancer Science Volume: 110 Issue: 10 Pages: 3061-3067
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• [Journal Article] Selective and competitive inhibition of kynurenine aminotransferase 2 by glycyrrhizic acid and its analogues (2019)
  • Author(s): Yoshida Yukihiro、Fujigaki Hidetsugu、Kato Koichi、Yamazaki Kyoka、Fujigaki Suwako、Kunisawa Kazuo、Yamamoto Yasuko、Mouri Akihiro、Oda Akifumi、Nabeshima Toshitaka、Saito Kuniaki
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 10243-10243
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• [Journal Article] Chronic unpredictable mild stress-induced behavioral changes are coupled with dopaminergic hyperfunction and serotonergic hypofunction in mouse models of depression (2019)
  • Author(s): Lu Qiaohui、Mouri Akihiro、Yang Yang、Kunisawa Kazuo、Teshigawara Tomoaki、Hirakawa Mami、Mori Yuko、Yamamoto Yasuko、Libo Zou、Nabeshima Toshitaka、Saito Kuniaki
  • Journal Title: Behavioural Brain Research Volume: 372 Pages: 112053-112053
  • DOI: 10.1016/j.bbr.2019.112053
  • Peer Reviewed
• [Journal Article] Changes in tryptophan metabolism during pregnancy and postpartum periods: Potential involvement in postpartum depressive symptoms (2019)
  • Author(s): Teshigawara Tomoaki、Mouri Akihiro、Kubo Hisako、Nakamura Yukako、Shiino Tomoko、Okada Takashi、Morikawa Mako、Nabeshima Toshitaka、Ozaki Norio、Yamamoto Yasuko、Saito Kuniaki
  • Journal Title: Journal of Affective Disorders Volume: 255 Pages: 168-176
  • DOI: 10.1016/j.jad.2019.05.028
  • Peer Reviewed
• [Journal Article] Effect of antidepressant treatment on plasma levels of neuroinflammation-associated molecules in patients with somatic symptom disorder with predominant pain around the orofacial region (2019)
  • Author(s): Tomoya Miyauchia, Tatsuya Tokuraa,*, Hiroyuki Kimuraa, Mikiko Itob, Eri Umemurab, Aiji Sato (boku)c, Wataru Nagashimad, Takashi Tonoikee, Yasuko Yamamotof, Kuniaki Saitof,g, Kenichi Kuritab, Norio Ozaki
  • Journal Title: Human Psychopharmacology: Clinical & Experimental Volume: 34 Issue: 4
  • DOI: 10.1002/hup.2698
  • NAID: 120006767392
  • Peer Reviewed
• [Journal Article] Decline of Plasma Concentrations of Interleukin-18 in Severely Malnourished Patients with Anorexia Nervosa: Exploratory Analysis. (2019)
  • Author(s): Tanaka S, Oya-Ito T, Murakami Y, Saito K, Furuta S, Yu Y, Imaeda M, Kunimoto S, Ozaki N.
  • Journal Title: Nutrients. Volume: 11(3) Issue: 3 Pages: 1-6
  • DOI: 10.3390/nu11030540
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• [Journal Article] Alteration of specific cytokine expression patterns in patients with breast cancer. (2019)
  • Author(s): Kawaguchi K, Sakurai M, Yamamoto Y, Suzuki E, Tsuda M, Kataoka TR, Hirata M, Nishie M, Nojiri T, Kumazoe M, Saito K, Toi M.
  • Journal Title: Sci Rep. Volume: 9 Issue: 1 Pages: 2924-2924
  • DOI: 10.1038/s41598-019-39476-9
  • NAID: 120006578938
  • Peer Reviewed / Open Access
• [Journal Article] Linking phencyclidine intoxication to the tryptophan-kynurenine pathway: Therapeutic implications for schizophrenia (2019)
  • Author(s): Fujigaki Hidetsugu、Mouri Akihiro、Yamamoto Yasuko、Nabeshima Toshitaka、Saito Kuniaki
  • Journal Title: Neurochemistry International Volume: 125 Pages: 1-6
  • DOI: 10.1016/j.neuint.2019.02.001
  • Peer Reviewed
• [Journal Article] Generalized Pustular Psoriasis from heterozygous IL36RN mutation developed after liver surgery. (2019)
  • Author(s): Fukushima H, Iwata Y, Numata, Saito K, Watanabe S, Kobayashi T, Sugiura K.
  • Journal Title: J Deramtol Volume: - Issue: 8
  • DOI: 10.1111/1346-8138.14828
  • Peer Reviewed / Open Access
• [Journal Article] Lipopolysaccharide shock reveals the immune function of indoleamine 2,3-dioxygenase 2 through the regulation of IL-6/stat3 signalling (2018)
  • Author(s): Yamamoto Yasuko、Yamasuge Wakana、Imai Shinjiro、Kunisawa Kazuo、Hoshi Masato、Fujigaki Hidetsugu、Mouri Akihiro、Nabeshima Toshitaka、Saito Kuniaki
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 15917-15917
  • DOI: 10.1038/s41598-018-34166-4
  • Peer Reviewed / Open Access
• [Journal Article] Excess maternal fructose consumption impairs hippocampal function in offspring via epigenetic modification of BDNF promoter. (2018)
  • Author(s): Yamazaki M, Yamada H, Munetsuna E, Ishikawa H, Mizuno G, Mukuda T, Mouri A, Nabeshima T, Saito K, Suzuki K, Hashimoto S, Ohashi K.
  • Journal Title: FASEB J. Volume: 32 Issue: 5 Pages: 2549-2562
  • DOI: 10.1096/fj.201700783rr
  • Peer Reviewed / Open Access
• [Journal Article] Fatigue-induced decline in low-frequency common input to bilateral and unilateral plantar flexors during quiet standing (2018)
  • Author(s): Watanabe Tatsunori、Saito Kotaro、Ishida Kazuto、Tanabe Shigeo、Nojima Ippei
  • Journal Title: Neuroscience Letters Volume: 686 Pages: 193-197
  • DOI: 10.1016/j.neulet.2018.09.019
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent Cutaneous Rosai-Dorfman Disease: A case Report. (2018)
  • Author(s): Yoshimoto N, Iwata Y, Numata S, Saito K, Iwata T, Arima M, Shima H, Tahara S, Kuroda M, Sugiura K.
  • Journal Title: Eur J Dermatol Volume: 28 Issue: 4 Pages: 562-563
  • DOI: 10.1684/ejd.2018.3348
  • Peer Reviewed
• [Presentation] トリプトファン代謝酵素 indoleamine 2,3-dioxygenase 2欠損が脳内に及ぼす影響 (2020)
  • Author(s): 石川雅樹、山本康子、齋藤邦明
  • Organizer: 第60回日本臨床化学会年次学術集会
• [Presentation] 疾患バイオマーカーとしてのトリプトファン ― キヌレニン経路 (2020)
  • Author(s): 山本康子、藤垣英嗣、齋藤邦明
  • Organizer: 第67回日本臨床検査医学会学術集会
• [Presentation] トリプトファン-キヌレニン代謝を基軸とした創薬・診断薬開発～皮膚科免疫関連疾患を視野に入れて～ (2020)
  • Author(s): 齋藤邦明
  • Organizer: 第71回日本皮膚科学会中部支部学術大会
  • Invited
• [Presentation] IDO1 regulates vulnerability to social defeat stress (2019)
  • Author(s): 國澤和生、毛利彰宏、小菅愛加、飯田翼、Wulaer Bolati、山本康子、齋藤邦明、鍋島俊隆
  • Organizer: NEURO2019（2019/7/25-28新潟）
  • Int'l Joint Research
• [Presentation] Involvement of Noradrenergic Function in the Behavioral Changes in MAGE-D1 KO Mice (2019)
  • Author(s): 毛利彰宏、平川茉実、渡辺研、國澤和生、森優子、窪田悠力、新島萌、山本康子、野田幸裕、鍋島俊隆、齋藤邦明
  • Organizer: NEURO2019（2019/7/25-28新潟）
  • Int'l Joint Research
• [Presentation] トリプトファン代謝経路が抑うつに与える影響-基礎研究と臨床研究のクロストーク- (2019)
  • Author(s): 毛利彰宏、國澤和生、窪田悠力、新島萌 、森優子、勅使河原知明、藤垣英嗣、山本康子、尾崎紀夫、齋藤邦明、鍋島俊隆
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム2019（2019/8/31東京）
• [Presentation] 感染症におけるオミックス解析の応用 (2019)
  • Author(s): 齋藤邦明
  • Organizer: 第60回日本臨床ウイルス学会（2019/5/25名古屋）
  • Invited
• [Presentation] IDO1は社会的敗北ストレス下におけるストレス脆弱性を制御する (2019)
  • Author(s): 國澤 和生 毛利 彰宏 小菅 愛加 飯田 翼 Wulaer Bolati 山本 康子 齋藤 邦明 鍋島 俊隆
  • Organizer: 第42回日本神経科学大会第62回日本神経化学会大会合同大会（2019/7/24-27新潟）
  • Int'l Joint Research
• [Presentation] Lipopolysaccharide injection triggers Indoleamine-2,3-dioxygenase1 and miR-874-3p interaction which leads to depression-like behavior in mouse (2019)
  • Author(s): Willy Jaya Suento, Kazuo Kunisawa, Bolati Wulaer, Tsubasa Iida, Aika Kosuge, Akihiro Mouri, Kuniaki Saito, Toshitaka Nabeshima
  • Organizer: AsCNP（2019/10/11-13福岡）
  • Int'l Joint Research
• [Presentation] The Role of Tryptophan Metabolism and Inflammation in Depression: The Target for Novel Diagnosis and Therapy藤 (2019)
  • Author(s): 齋藤邦明
  • Organizer: 藤田医科大学ブランディング事業国際シンポジウム（201910/14 名古屋）
  • Int'l Joint Research / Invited
• [Presentation] トリプトファン-キヌレニン代謝をターゲットとした創薬・診断薬開発 (2019)
  • Author(s): 齋藤邦明
  • Organizer: 第39回日本トリプトファン研究会学術集会（2019/12/14-15千葉）
  • Invited
• [Presentation] NGSを用いた小脳変性マウスのExome解析および原因遺伝子候補の神経栄養因子との関連 脳機能改善素材開発試験の応用を目指して (2018)
  • Author(s): 別府 秀彦, 稲垣 秀人, 西井 一宏, 新里 昌功, 千原 猛, 毛利 彰宏, 齋藤 邦明, 高橋 久英, 倉橋 浩樹
  • Organizer: 第１６回日本機能性食品医用学会
• [Presentation] 糖尿病モデルマウスにおけるキヌレニン経路代謝物の腎組織イメージング質量分析 (2018)
  • Author(s): 松下 祥子, 高橋 和男, 伊藤 辰将, 山本 康子, 藤垣 英嗣, 毛利 彰宏, 中嶋 和紀, 尾之内 高慶, 辰川 英樹, 釘田 雅則, 長尾 静子, 人見 清隆, 齋藤 邦明, 瀬藤 光利, 湯澤 由紀夫
  • Organizer: 第61回日本腎臓学会学術総会
• [Presentation] 薬学研究が支える臨床化学 精神疾患モデル動物研究からのバイオマーカー研究 薬学・医学から臨床化学へのトランスレーショナル研究 (2018)
  • Author(s): 毛利 彰宏, 國澤 和生, 山本 康子, 齋藤 邦明, 鍋島 俊隆
  • Organizer: 第５８回日本臨床化学会年次学術集会
• [Presentation] 10年後の臨床化学を考える 診断薬開発の未来 求められる先制診断システム (2018)
  • Author(s): 齋藤邦明
  • Organizer: 第５８回日本臨床化学会年次学術集会
  • Invited
• [Presentation] 酵素反応を用いたキノリン酸測定法の開発 (2018)
  • Author(s): 山崎 杏佳, 藤垣 英嗣, 吉田 幸弘, 木村 文香, 山本 康子, 齋藤 邦明
  • Organizer: 第５８回日本臨床化学会年次学術集会
• [Presentation] 神経精神疾患の病態メカニズムに基づく新たな治療分子標的 トリプトファン代謝に注目したうつ病病態解明と診断・治療薬戦略 (2018)
  • Author(s): 毛利 彰宏, 國澤 和生, 山本 康子, 藤垣 英嗣, 齋藤 邦明, 鍋島 俊隆
  • Organizer: 第２８回日本臨床精神神経薬理学会・第４８回日本神経精神薬理学会合同年会
• [Presentation] ストレス(モデル)と分子 うつ病発症におけるトリプトファン代謝の関与 (2018)
  • Author(s): 國澤 和生, 毛利 彰宏, 山本 康子, 齋藤 邦明, 鍋島 俊隆
  • Organizer: 第34回日本ストレス学会学術総会
• [Presentation] Prostaglandin E receptor subtype EP1 deficiency elicits AD/HD-like behavior correlated with a dysfunction of dopamine D1 receptor-ERK signaling in the prefrontal cortex (2018)
  • Author(s): Akihiro Mouri, Tomoyuki Furuyashiki, Kazuo Kunisawa, Yasuko Yamamoto, Kiyofumi Yamada, Yukihiro Noda, Kuniaki Saito, Shu Narumiya, TOshitaka Nabeshima
  • Organizer: WCP2018 Kyoto
  • Int'l Joint Research
• [Presentation] Involvement of kynurenine 3-monooxygenase in the vulnerability to the PCP-induced behavioral abnormalities (2018)
  • Author(s): Hisayoshi Kubota, Akihiro Mouri, Kazuo Kunisawa, Moe Niijima, Tomoaki Teshigawara, Mami Hirakawa, Yuko Mori, Yasuko Yamamoto, Toshitaka Nabeshima ,Kuniaki Saito
  • Organizer: WCP2018 Kyoto
  • Int'l Joint Research
• [Presentation] Exposure to valproic acid during pregnancy induces autism endophenotypes in the male offspring (2018)
  • Author(s): Mami HIrakawa, Akihiro Mouri, Kazuo Kunisawa, Yuko Mori, Moe Niijima ,Hisayoki Kubota, Tomoaki Teshigawara, Hidetsugu Fujigaki, Toshitaka Nabeshima, Kuniaki Saito
  • Organizer: WCP2018 Kyoto
  • Int'l Joint Research
• [Presentation] Development of animal models and biomarker for depression focused on serotonergic systems (2018)
  • Author(s): Akihiro Mouri, Kazuo Kunisawa, Hidetsugu Fujigaki, Yasuko Yamamoto , Kuniaki Saito, Toshitaka Nabeshima
  • Organizer: 15th International Society for Tryptophan Research (ISTRY) Conference
  • Int'l Joint Research
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