研究活動情報

• Impact of prenatal manganese and selenium exposure on childhood thyroid hormone parameters up to 4 years of age: Japan environment and children’s study
  Takeshi Yamaguchi; Hiroyoshi Iwata; Sachiko Itoh; Yu Ait Bamai; Atsuko Ikeda; Keitaro Makino; Mariko Itoh; Rahel Mesfin Ketema; Naomi Tamura; Rieko Yamamoto; Maki Tojo; Kensuke Oba; Shuntaro Morikawa; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  Environment International, 110353, 110353, Elsevier BV, 2026年06月
  研究論文（学術雑誌）
• Latent class analysis of mobile phone usage patterns and association with sleep problems in children: Findings from the Hokkaido Birth Cohort Study
  Ammara Ajmal; Naomi Tamura; Yu Ait Bamai; Keiko Yamazaki; Toshio Yoshikawa; Rieko Yamamoto; Mariko Itoh; Keitaro Makino; Takashi Hikage; Tatsuya Kashiwa; Toshihiko Nishimura; Atsuko Ikeda; Reiko Kishi
  Computers in Human Behavior Reports, 22, 101077, 101077, Elsevier BV, 2026年05月
  研究論文（学術雑誌）
• The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: the Japan environment and children’s study
  Akira Oku; Yoshihiro Saito; Hiroyoshi Iwata; Sachiko Itoh; Ami Hosokawa; Takeshi Yamaguchi; Mariko Itoh; Keitaro Makino; Maki Tojo; Hidemichi Watari; Yoshiya Ito; Yasuaki Saijo; Reiko Kishi; Michihiro Kamijima; Shin Yamazaki; Maki Fukami; Reiko Kishi; Chiharu Ota; Koichi Hashimoto; Kenichi Sakurai; Shuichi Ito; Ryoji Shinohara; Hidekuni Inadera; Takeo Nakayama; Ryo Kawasaki; Yasuhiro Takeshima; Hideki Nagashima; Narufumi Suganuma; Mayumi Tsuji; Kimitoshi Nakamura
  BMC Pregnancy and Childbirth, Springer Science and Business Media LLC, 2026年03月06日
  研究論文（学術雑誌）
• The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: the Japan environment and children’s study
  Akira Oku; Yoshihiro Saito; Hiroyoshi Iwata; Sachiko Itoh; Ami Hosokawa; Takeshi Yamaguchi; Mariko Itoh; Keitaro Makino; Maki Tojo; Hidemichi Watari; Yoshiya Ito; Yasuaki Saijo; Reiko Kishi; Michihiro Kamijima; Shin Yamazaki; Maki Fukami; Reiko Kishi; Chiharu Ota; Koichi Hashimoto; Kenichi Sakurai; Shuichi Ito; Ryoji Shinohara; Hidekuni Inadera; Takeo Nakayama; Ryo Kawasaki; Yasuhiro Takeshima; Hideki Nagashima; Narufumi Suganuma; Mayumi Tsuji; Kimitoshi Nakamura
  BMC Pregnancy and Childbirth, Springer Science and Business Media LLC, 2026年03月06日
  研究論文（学術雑誌）
• Associations of prenatal exposure to organophosphate pesticides with eczema and allergic rhinoconjunctivitis in 4-year-old children: The Japan Environment and Children's Study
  Megasari Marsela; Hiroyoshi Iwata; Yu Ait Bamai; Mariko Itoh; Rahel Mesfin Ketema; Takeshi Yamaguchi; Yasuaki Saijo; Yoshiya Ito; Sachiko Itoh; Keiko Yamazaki; Naomi Tamura; Keitaro Makino; Maki Tojo; Reiko Kishi; Atsuko Ikeda
  Environmental Research, 123839, 123839, Elsevier BV, 2026年02月
  研究論文（学術雑誌）
• Effects of maternal occupation on low birth weight and preterm birth: A prospective birth cohort study in the first trimester, the Japan environment and Children's study.
  Sumitaka Kobayashi; Hiroyoshi Iwata; Takeshi Yamaguchi; Naomi Tamura; Mariko Itoh; Maki Tojo; Keiko Yamazaki; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 172, 2, 991, 1008, 2026年02月, ［国際誌］
  英語, 研究論文（学術雑誌）, OBJECTIVE: Although there are some reports that maternal occupation during pregnancy decreases birth size, the results are inconsistent. Hence, we examined the association of maternal occupation during pregnancy with infant low birth weight (LBW) and preterm birth (PB). METHODS: We used data from 53 932 participants of the prospective birth cohort of the Japan Environment and Children's Study. During the first trimester, information on maternal occupational major and minor groups, type of employment, and average weekly working hours was obtained using a self-administered questionnaire. Information on LBW and PB was obtained from medical records transcribed by physicians, midwives/nurses, and/or research coordinators at birth. Associations between maternal occupation and birth outcomes were examined using logistic regression models adjusted for confounding factors. RESULTS: In the major occupational group, the odds ratio (95% confidence interval) of LBW in administrative and managerial workers (0.52; 0.32-0.84) was lower than that in professional and engineering workers. Among administrative and managerial workers, the percentages of LBW among management government officials (4.6%), officers of companies and organizations (4.0%), and management staff of companies and organizations (7.1%) were lower than the overall average of 8.2%. Similar results were found for LBW at full-term (Term-LBW; ≥37 weeks of gestational age). However, there were no associations between the maternal major occupational groups on PB. We observed the association of maternal occupation in the first trimester on infant LBW and Term-LBW. CONCLUSION: The results suggest that medical professionals need to advise considering maternal occupation when performing pregnancy checkups.
• Childhood obesity and DNA methylation in an epigenome-wide association study: findings from the Hokkaido Birth Cohort
  Hiroyoshi Iwata; Chihiro Miyashita; Takeshi Yamaguchi; Atsuko Ikeda; Ryu Miura; Machiko Minatoya; Naomi Tamura; Yu Ait Bamai; Sachiko Itoh; Keiko Yamazaki; Rahel Mesfin Ketema; Mariko Itoh; Maki Tojo; Rieko Yamamoto; Keitaro Makino; Reiko Kishi
  Clinical Epigenetics, Springer Science and Business Media LLC, 2025年12月01日
  研究論文（学術雑誌）
• Toxic metals and trace elements in maternal blood and urinary tract infection during the first 2 years of life: The Japan Environment and Children's Study
  Keitaro Makino; Hiroyoshi Iwata; Takeshi Yamaguchi; Atsuko Ikeda; Yu Ait Bamai; Sachiko Itoh; Mariko Itoh; Maki Tojo; Naomi Tamura; Rieko Yamamoto; Rahel Mesfin Ketema; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  Science of The Total Environment, 1006, 180895, 180895, Elsevier BV, 2025年12月
  研究論文（学術雑誌）
• Decreased non-emotional working memory capacity in women with PTSD: association with symptomatology.
  Natsuki Ueda; Mingming Lin; Mariko Itoh; Hiroaki Hori; Zui Narita; Madoka Niwa; Keiko Ino; Megumi Narita; Wakako Nakano; Risa Imai; Mie Matsui; Toshiko Kamo; Yoshiharu Kim
  European journal of psychotraumatology, 16, 1, 2543079, 2543079, 2025年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, Background/objective: Posttraumatic stress disorder (PTSD) is known to be associated with deficits in working memory (WM). However, findings regarding the relationship of PTSD with non-emotional WM have not necessarily been uniform. This study aimed to clarify the relationship between PTSD and non-emotional WM using the N-back task, a well-established WM task.Method: A total of 111 women with PTSD and 120 healthy control women without trauma were enrolled. Most of the patients developed PTSD after experiencing interpersonal violence. Participants completed 0-back and 2-back tasks using non-emotional stimuli (number), as well as a standardised neuropsychological test battery and self-report questionnaires for PTSD and depression symptoms.Results: The PTSD group showed significantly less accuracy in the 2-back task than the control group, while no significant difference was observed in the accuracy of the 0-back task. The PTSD group showed significantly prolonged reaction time compared to controls in both the 0-back and 2-back tasks. The prolonged reaction time in the 2-back task was significantly correlated with more severe overall symptoms and avoidance symptoms in the PTSD group after controlling for age.Conclusion: Individuals with PTSD exhibited reduced WM capacity. Drawing on a relatively large civilian sample, this study contributes to the accumulating evidence of such deficits. Notably, the observed association between WM dysfunction and avoidance symptoms suggests a symptom-specific cognitive profile in PTSD.
• The impact of pediatric constipation on appendicitis: a prospective birth cohort in the Japan Environment and Children's Study.
  Hiroyoshi Iwata; Takeshi Yamaguchi; Sachiko Itoh; Yu Ait Bamai; Atsuko Ikeda; Keitaro Makino; Mariko Itoh; Maki Tojo; Rieko Yamamoto; Naomi Tamura; Rahel Mesfin Ketema; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  BMC pediatrics, 25, 1, 962, 962, 2025年11月26日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: This study aimed to examine the association between constipation and appendicitis in children using data from a nationwide birth cohort, the Japan Environment and Children's Study (JECS). METHODS: Data were obtained from 64,772 children and their mothers participating in JECS, which included over 100,000 pregnancies across 15 regional centres in Japan. Pediatric constipation was assessed at age three using the Rome III criteria, while appendicitis cases were identified between ages three to four. Logistic regression analyses, including univariable and multivariable models, were conducted to evaluate associations. Additional analyses were stratified by sex. RESULTS: Among the 64,772 children analyzed, 156 cases of appendicitis were identified between the ages of 3 and 4 years. Logistic regression suggested a possible association between constipation and an increased risk of appendicitis (univariable odds ratio [OR]: 1.38, 95% confidence interval [CI]: 0.87–2.10; multivariable OR: 1.36, 95% CI: 0.86–2.06). Although the associations did not reach statistical significance, the point estimates consistently indicated a trend toward increased risk. CONCLUSION: Although our analyses of children aged 3–4 years did not yield statistically significant associations, the observed trends may suggest a potential link between constipation and appendicitis. These findings should be interpreted only as exploratory, and further studies in different age groups, including older children and adults, are warranted to confirm or refute this possible association. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12887-025-06263-7.
• Prediction of Kawasaki disease coronary artery lesions in the Japan Environment and Children’s Study
  Hiroyoshi Iwata; Takeshi Yamaguchi; Naomi Tamura; Yu Ait Bamai; Atsuko Ikeda; Mariko Itoh; Rieko Yamamoto; Maki Tojo; Rahel Mesfin Ketema; Keiko Yamazaki; Sachiko Itoh; Keitaro Makino; Satoru Shida; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  Annals of Pediatric Cardiology, 18, 5, 437, 446, Ovid Technologies (Wolters Kluwer Health), 2025年09月
  研究論文（学術雑誌）, Objective:
  
  This study aimed to validate a composite of previously identified risk factors for predicting coronary artery lesions in Japanese children with Kawasaki Disease (KD).
  
  Materials and Methods:
  
  Children diagnosed with KD from the Japan Environment and Children’s Study (JECS) cohort were included. We assessed the discriminative ability of the model using the area under the curve (AUC) and evaluated its calibration using calibration plots. Based on clinical insights, we derived our original model, which consisted of variables established in previous score models or studies. Using the bootstrap method, internal validation was assessed with the AUC and calibration slope.
  
  Results:
  
  Our analysis included 959 children with KD, derived from 104,062 pediatric records contained in the JECS. Our model comprised the following variables: sex, hematocrit, platelet count, C-reactive protein, and serum sodium levels. The mean and 95% confidence intervals of the AUCs for the Harada, Egami, and Kobayashi models were 0.66 (0.59–0.72), 0.59 (0.52–0.66), and 0.64 (0.56–0.72), respectively. Our score model with bootstrap analyses produced an AUC of 0.80 (0.68–0.91) and a calibration slope of 1.01.
  
  Conclusions:
  
  We built and evaluated our score model using indicators that were easily accessible with a moderate-to-high AUC and stable calibration results, indicating the high reliability of the model for clinical application. Further studies are required to validate our model in other cohorts.
• PTSD患者および健常対照者における血清脂質および血漿脂肪酸プロファイル 症状・認知機能・炎症マーカーとの関連
  小川 眞太朗; 堀 弘明; 丹羽 まどか; 伊藤 真利子; 林 明明; 吉田 冬子; 井野 敬子; 河西 ひとみ; 成田 恵; 中野 稚子; 今井 理紗; 松井 三枝; 加茂 登志子; 功刀 浩; 服部 功太郎; 金 吉晴
  国立精神・神経医療研究センター精神保健研究所年報, 38, 200, 200, (国研)国立精神・神経医療研究センター精神保健研究所, 2025年09月
  日本語
• Impact of prenatal exposure to per- and polyfluoroalkyl substances on developmental delays in 4-year-old children: The Japan Environment and Children’s study
  Mariko Itoh; Sumitaka Kobayashi; Hiroyoshi Iwata; Yu Ait Bamai; Rahel Mesfin Ketema; Takeshi Yamaguchi; Keiko Yamazaki; Naomi Tamura; Maki Tojo; Satoshi Suyama; Sachiko Itoh; Chihiro Miyashita; Yasuaki Saijo; Yoshiya Ito; Shoji F. Nakayama; Michihiro Kamijima; Reiko Kishi
  Environment International, 198, 109434, 109434, Elsevier BV, 2025年04月
  研究論文（学術雑誌）
• Mediation of prenatal cotinine and 8-hydroxy-2’-deoxyguanosine levels on infant birth size in the Japan Environment and Children’s Study (JECS)
  Sumitaka Kobayashi; Hiroyoshi Iwata; Takeshi Yamaguchi; Naomi Tamura; Mariko Itoh; Maki Tojo; Keiko Yamazaki; Sachiko Itoh; Chihiro Miyashita; Yu Ait Bamai; Yukihiro Sato; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  Reproductive Toxicology, 108905, 108905, Elsevier BV, 2025年04月
  研究論文（学術雑誌）
• Association between prenatal exposure to maternal metal and trace elements and Streptococcus infection: A prospective birth cohort in the Japan Environment and Children’s Study
  Hiroyoshi Iwata; Atsuko Ikeda; Mariko Itoh; Rahel Mesfin Ketema; Naomi Tamura; Takeshi Yamaguchi; Keiko Yamazaki; Rieko Yamamoto; Maki Tojo; Yu Ait Bamai; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  PLOS ONE, 20, 2, e0319356, e0319356, Public Library of Science (PLoS), 2025年02月27日
  研究論文（学術雑誌）, Background
  
  Streptococcus infection is a common and potentially severe bacterial infection which remains a global public health challenge, underscoring the necessity of investigating potential risk factors.
  
  Aims
  
  The present study aims to assess the association between metal and trace element exposure and Streptococcus infection using a prospective nationwide birth cohort, the Japan Environment and Children’s Study (JECS).
  
  Methods
  
  The JECS obtained data from over 100,000 pregnancies through 15 Regional Centres across Japan. We assessed toxic metal and trace element levels among pregnant mothers and Streptococcus infection among their children, born between 2011 and 2014, at age three to four. Analysis was performed using univariable and multivariable logistic regressions, as well as Quantile g-computation. We also conducted quartile regressions to assess the effects of higher serum selenium levels and potential interactions between selenium and mercury.
  
  Results
  
  Among 74,434 infants and their mothers, univariable and multivariable regression analyses found that selenium and mercury each had an inverse association with Streptococcus infection incidence. Quantile g-computation analysis yielded results consistent with the primary regression analyses. Quartile regression suggested that serum selenium levels above the third quartile were inversely associated with later Streptococcus infection incidence, but no interaction between selenium and mercury was found.
  
  Conclusions
  
  These findings imply that maternal selenium exposure may have protective effects on Streptococcus infection among children. Further studies should explore the role of pediatric selenium in immune responses to infectious diseases, especially Streptococcus infection.
• Serum lipid and plasma fatty acid profiles in PTSD patients and healthy individuals: Associations with symptoms, cognitive function, and inflammatory markers.
  Shintaro Ogawa; Hiroaki Hori; Madoka Niwa; Mariko Itoh; Mingming Lin; Fuyuko Yoshida; Keiko Ino; Hitomi Kawanishi; Megumi Narita; Wakako Nakano; Risa Imai; Mie Matsui; Toshiko Kamo; Hiroshi Kunugi; Kotaro Hattori; Yoshiharu Kim
  Progress in neuro-psychopharmacology & biological psychiatry, 111298, 111298, 2025年02月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, Increasing evidence suggests that posttraumatic stress disorder (PTSD), a serious mental health condition, is associated with physical health problems. Lipid-related molecules are crucial for central nervous system functions associated with PTSD symptoms; however, case-control studies exploring the relationship between PTSD and lipid-related molecules are scarce. We examined 68 civilian PTSD patients and 97 healthy controls, evaluating PTSD symptoms, childhood maltreatment history, suicidality, and cognitive functions. Cholesterol, triglycerides, and inflammation-related marker levels were analyzed in serum, while fatty acid levels were measured in plasma. Compared to controls, patients exhibited significantly lower high-density lipoprotein cholesterol and n-6 linoleic acid levels, alongside higher saturated palmitic acid levels and the triene-to-tetraene (T/T) ratio. PTSD symptoms, particularly hyperarousal, were significantly positively correlated with n-6 γ-linolenic, n-6 dihomo-γ-linolenic, and n-9 mead acid levels, and the T/T ratio. Cognitive functions were significantly positively correlated with n-3 docosahexaenoic acid and total n-3 fatty acid levels, and negatively correlated with dihomo-γ-linolenic, palmitic, and total saturated fatty acid levels. Suicidality was significantly positively correlated with dihomo-γ-linolenic acid, mead acid levels, and the T/T ratio, and negatively correlated with polyunsaturated fatty acid (PUFA) levels. Inflammation-related marker levels were significantly correlated with higher palmitic, n-9 oleic, and total n-9 fatty acid levels, and lower linoleic acid and PUFA levels. Latent profile analysis (LPA) revealed distinct subgroups associated with unique fatty acid profiles. These lipid-related alterations may improve the understanding of PTSD pathophysiology. Distinct fatty acid profiles identified by LPA may help subtype PTSD patients and guide nutrition-based personalized treatment strategies.
• Association between small for gestational age and neurodevelopmental disability at 5 years in the Hokkaido study.
  Satoshi Suyama; Mariko Itoh; Naomi Tamura; Hiroyoshi Iwata; Takeshi Yamaguchi; Sumitaka Kobayashi; Chihiro Miyashita; Takuya Saito; Reiko Kishi
  Pediatrics international : official journal of the Japan Pediatric Society, 67, 1, e70137, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Low birth weight is a known risk factor for delayed growth and disability in children. It is assessed using a measure called small for gestational age (SGA). SGA children have an increased risk of neurodevelopmental disabilities, regardless of gestational age. We conducted this study to evaluate the effects of SGA on neurodevelopmental disability, particularly in SGA full-term newborns (term-SGA). METHODS: This study was conducted using a prospective birth cohort from the Hokkaido Study on Environment and Children's Health. The mothers of 4851 children who reached the age of 5 years between April 2008 and November 2011 received questionnaires, including the strengths and difficulties questionnaire (SDQ). Neurodevelopmental disability was assessed using the SDQ. SGA infants, including term-SGA, were assessed by referring to the birth weight database of the Japan Pediatric Society. RESULTS: We received 3484 responses from the parents. Univariate analysis revealed a significant difference in hyperactivity/inattention and the total difficulties score (TDS) between groups defined as normal and borderline/clinical based on the TDS, for both SGA and term-SGA infants. In the multivariate analysis, sex, household income, and SGA and term-SGA status were significantly associated with TDS (term-SGA: odds ratio [OR] = 1.72; 95% confidence interval [CI], 1.07-2.76; SGA, OR = 1.75; 95% CI: 1.10-2.78). However, SGA and term-SGA status were not associated with hyperactivity/inattention. CONCLUSIONS: SGA, even at term, may predispose children to neurodevelopmental disability.
• Japanese growth charts stratified by birth weight in 500-gram increments: findings from the Japan environment and children’s study
  Takeshi Yamaguchi; Naomi Tamura; Hiroyoshi Iwata; Sachiko Itoh; Mariko Itoh; Maki Tojo; Keitaro Makino; Yasuaki Saijo; Akie Nakamura; Yoshiya Ito; Kazutoshi Cho; Akinori Moriichi; Yumi Kono; Taro Yamauchi; Reiko Kishi
  Clinical Pediatric Endocrinology, Japanese Society for Pediatric Endocrinology, 2025年
  研究論文（学術雑誌）
• Association between prenatal tobacco exposure and attention-deficit/hyperactivity disorder related characteristics at 6 and 8 years: a birth cohort in Japan
  Mariko Itoh; Sumitaka Kobayashi; Shinkichi Nishihara; Chihiro Miyashita; Keiko Yamazaki; Naomi Tamura; Satoshi Suyama; Atsuko Ikeda; Sachiko Itoh; Yu Ait Bamai; Takeshi Yamaguchi; Hideyuki Masuda; Sharon Hanley; Reiko Kishi
  BMJ Open, 14, 12, e087406, e087406, BMJ, 2024年12月26日
  研究論文（学術雑誌）, Objectives
  
  To examine the association between maternal plasma cotinine concentrations during pregnancy and attention-deficit/hyperactivity disorder (ADHD) related characteristics in children.
  
  Design
  
  Prospective birth cohort study from the Hokkaido Study on Environment and Children’s Health.
  
  Setting
  
  Hokkaido, Japan.
  
  Participants
  
  A total of 7217 children were included in the analysis. Their mothers were recruited to this study between 2003 and 2012 during early pregnancy. Blood samples of mothers in their third trimester of pregnancy were obtained.
  
  Main outcome measures
  
  ADHD-related characteristics screened by the ADHD-Rating Scale (ADHD-RS) in children at 6 and 8 years of age.
  
  Results
  
  The mothers were classified into three groups according to plasma cotinine levels (median=0.22 ng/mL)—non-smokers (≤0.21 ng/mL), passive smokers (0.22–11.48 ng/mL) and active smokers (≥11.49 ng/mL). ADHD was suspected in 302 (8.6%), 334 (10.9%) and 90 (14.5%) children in the non-smoker, passive smoker and active smoker groups, respectively. Children born to mothers in the smoking group had a statistically significant increased risk of ADHD-related characteristics (adjusted RR=1.49, 95% CI=1.19–1.86 and adjusted RR=1.20, 95% CI=1.03–1.40 for the active and passive smoking groups, respectively).
  
  Conclusion
  
  This large Japanese cohort study suggests an association between smoking during pregnancy and the risk of ADHD in children 6 and 8 years of age.
• Effects of the maternal work environment on psychological distress during pregnancy: A cross-sectional research-The Japan Environment and Children’s Study
  Sumitaka Kobayashi; Yasuaki Saijo; Mariko Itoh; Naomi Tamura; Maki Tojo; Hiroyoshi Iwata; Takeshi Yamaguchi; Yoshiya Ito; Reiko Kishi
  Journal of Occupational & Environmental Medicine, Ovid Technologies (Wolters Kluwer Health), 2024年11月19日
  研究論文（学術雑誌）, Abstract
  
  Objectives
  
  As part of the “Japan Environment and Children’s Study (JECS),” a national prospective birth cohort study, we examined the association between the maternal work environment and psychological distress during pregnancy in Japan.
  
  Methods
  
  Employing a cross-sectional design, we analyzed data from 42,797 participants, originally collected between 2011 and 2014. Associations between the maternal work environment and psychological distress (Kessler 6) were examined using generalized estimation equation models adjusted for confounding factors.
  
  Results
  
  Pregnant women who worked ≥51 h/week had a 1.19-fold higher odds ratio (OR) of psychological distress than those who worked 36-40 h/week (95% confidence intervals [CI], 1.07-1.32). Pregnant women who worked ≥5 days/month of shift work had a 1.11-fold higher OR of psychological distress than those who worked 0 days/month (1.00-1.24).
  
  Conclusions
  
  We observed an association between the maternal work environment and psychological distress during pregnancy.
• Association between the occupation of pregnant women’s partners and risks of infant low birth weight and preterm birth in a prospective birth cohort: the Japan Environment and Children’s Study
  Sumitaka Kobayashi; Yasuaki Saijo; Hiroyoshi Iwata; Takeshi Yamaguchi; Naomi Tamura; Mariko Itoh; Maki Tojo; Yoshiya Ito; Reiko Kishi
  Journal of Occupational & Environmental Medicine, Ovid Technologies (Wolters Kluwer Health), 2024年11月19日
  研究論文（学術雑誌）, Abstract
  
  Objective
  
  We examined the association between the occupations of pregnant women’s partners and infant low birth weight (LBW) and preterm birth (PB).
  
  Methods
  
  Birth outcome data were collected from 46,540 participants enrolled in the Japan Environment and Children’s Study. Participants were recruited from January 2011 to March 2014. Associations between the occupations of pregnant women’s partners and birth outcomes were examined using logistic regression models adjusted for confounding factors.
  
  Results
  
  LBW and PB incidences were 7.5% and 4.1%, respectively. In the major occupational group, the odds ratios (95% confidence intervals) of LBW for clerical (1.19; 1.03-1.37) and service workers (1.21; 1.05-1.39) were higher than those for professional and engineering workers. However, no associations existed between the major occupational groups of the pregnant women’s partners and PB.
  
  Conclusion
  
  Partner’s employment in clerical and service work increases the risk for LBW.
• Association between small for gestational age and motor coordination difficulties in children aged 5-6 years: Insights from the Hokkaido Study on Environment and Children's Health.
  Maki Tojo; Hiroyoshi Iwata; Naomi Tamura; Takeshi Yamaguchi; Kenji J Tsuchiya; Satoshi Suyama; Taku Obara; Akio Nakai; Toshio Yoshikawa; Toyoki Yamagata; Mariko Itoh; Keiko Yamazaki; Sumitaka Kobayashi; Reiko Kishi
  Brain & development, 47, 1, 104296, 104296, 2024年11月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Developmental coordination disorder (DCD) presents motor skill delays in early childhood and has been associated with later maladaptation, necessitating early intervention. However, research on the potential risk factors, particularly in preschool-aged children, remains scarce. AIMS: We aimed to explore the association between small for gestational age (SGA) and other factors and motor coordination problems in 5-6-year-olds from the Hokkaido Study on Environment and Children's Health Cohort. STUDY DESIGN: Prospective. SUBJECTS: We analyzed data from >3500 participants from the Hokkaido Study, a prospective birth cohort, and assessed children aged 5-6 years. OUTCOME MEASURES: Participants underwent assessment with the Developmental Coordination Disorder Questionnaire Japanese version (DCDQ-J). We conducted linear regression analyses adjusted for variables such as the child's sex, maternal age, and maternal smoking history during pregnancy, while also examining the independent associations of each risk factor. RESULTS: Among the 3883 children analyzed for SGA, children with SGA exhibited significantly lower DCDQ-J total scores than non-SGA children (mean difference: -2.25, 95 % confidence interval [-4.19, -0.30], p = 0.02). On the subscales, children with SGA demonstrated significantly lower "Control During Movement" scores than non-SGA children (mean difference: -0.96, 95 % confidence interval [-1.78, -0.13], p = 0.02). Furthermore, the child's sex, maternal smoking, maternal age, and preterm birth were independently associated with DCD. CONCLUSIONS: SGA was shown to be one of the risk factors for the manifestation of motor coordination difficulties in 5-6-years old children. In combination with other factors, screening for motor coordination difficulties in SGA children will be an important means of initiating appropriate interventions.
• Heavy metals and trace elements in maternal blood and prevalence of congenital limb abnormalities among newborns: the Japan Environment and Children's Study.
  Atsuko Ikeda; Megasari Marsela; Chihiro Miyashita; Takeshi Yamaguchi; Yasuaki Saijo; Yoshiya Ito; Hiroyoshi Iwata; Sachiko Itoh; Mariko Itoh; Keiko Yamazaki; Naomi Tamura; Sumitaka Kobayashi; Reiko Kishi
  Environmental health and preventive medicine, 29, 36, 36, 2024年, ［国内誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Heavy metals such as lead (Pb) and cadmium (Cd) have been associated with adverse pregnancy and developmental outcomes, including congenital abnormalities. This study investigated the association between exposure to heavy metals and trace elements during fetal life and congenital limb abnormalities in infants. METHODS: This study is based on a prospective ongoing nationwide birth cohort from the Japan Environment and Children's Study (JECS). The concentrations of Cd, Pb, mercury (Hg), selenium (Se), and manganese (Mn) were measured in maternal blood collected during the mid-late trimesters. Inclusion criteria were available from questionnaires filled in during pregnancy, including information about congenital limb abnormalities at birth or at one month. To examine the associations with limb anomalies and individual chemicals, logistic regression models were applied following log-transformation or division into quartiles of Cd, Pb, Hg, Se, and Mn concentrations. To assess the associations with the heavy metals and trace elements mixture, quantile g-computation was employed. All models were adjusted for age, maternal smoking history, maternal alcohol intake, history of smoking, and infant sex. RESULTS: Data from 90,163 participants were included in the analysis, of whom 369 had congenital limb abnormalities in any of the collected information, and 89,794 had none. Among the 369 cases of congenital limb abnormalities, there were 185 and 142 cases of polydactyly and syndactyly, respectively. The median concentrations of Pb, Cd, Hg, Se, and Mn were 5.85, 0.66, 3.64, 168, and 15.3 ng/g, respectively. There were no associations between maternal blood concentrations of Pb [adjusted odd ratio = 0.83; 95% confidence interval = 0.61, 1.11], Cd [0.87; 0.68, 1.10], Hg [0.88; 0.73, 1.07], Se [1.07; 0.44, 2.59], and Mn [0.91; 0.64, 1.30] with congenital limb abnormalities. No significant association was observed between the mixture of heavy metals and trace elements [0.85; 0.72, 1.02] and any congenital limb abnormalities. Moreover, there was no association with all polydactylies and all syndactylies, or any type of abnormality as a subdivision. CONCLUSION: At the maternal exposure levels of Cd, Pb, Hg, Se, and Mn assessed in the present study, no association was identified with the risk of developing congenital limb abnormalities in children.
• The association between flooring materials and childhood asthma: A prospective birth cohort in the Japan Environment and Children's Study.
  Hiroyoshi Iwata; Atsuko Ikeda; Mariko Itoh; Sachiko Itoh; Rahel Mesfin Ketema; Naomi Tamura; Chihiro Miyashita; Takeshi Yamaguchi; Keiko Yamazaki; Rieko Yamamoto; Maki Tojo; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  PloS one, 19, 7, e0305957, 2024年, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Childhood asthma is known to be affected by a range of factors, including conditions in the indoor environment. While flooring material influences indoor air conditions, the potential association between flooring materials and childhood asthma remains poorly understood in Japan. OBJECTIVE: The present study aims to assess the association between childhood asthma incidence and the primary flooring material with the ongoing prospective nationwide birth cohort data of the Japan Environment and Children's Study (JECS). METHODS: The JECS gathered data on mothers and children through 15 Regional Centres across Japan. The present study assessed flooring materials used in the home and asthma incidence at age four among children born between 2011 and 2014. We implemented logistic regressions, setting asthma incidence among the children as the outcome and home floor type as the exposure. Additional analyses were conducted, stratifying the home's age as a proxy for tatami age, to assess whether the potential effect of tatami flooring on asthma risk is influenced by its age. RESULTS: The present study included total of 75,629 infants. For tatami flooring, the main multivariable regression and additional sub-group regression for homes over ten years old produced odds ratios of 1.09; 95% Confidence Interval (CI) [1.01-1.17] and 1.10; 95% CI [1.00-1.21] compared with flooring, respectively. CONCLUSION: These results imply that exposure to tatami flooring, particularly in older homes, may be associated with childhood asthma incidence. Moreover, our study highlights the importance of evaluating the relationship between regional and cultural differences between asthma and flooring materials.
• Hokkaido birth cohort study in Japan on the growth trajectory of children born with low birth weight until 7 years of age
  Kritika Poudel; Sumitaka Kobayashi; Hiroyoshi Iwata; Maki Tojo; Takeshi Yamaguchi; Keiko Yamazaki; Naomi Tamura; Mariko Itoh; Taku Obara; Shinichi Kuriyama; Reiko Kishi
  Early Human Development, 105925, 105925, Elsevier BV, 2023年12月
  研究論文（学術雑誌）
• The association between prenatal per-and polyfluoroalkyl substance levels and Kawasaki disease among children of up to 4 years of age: A prospective birth cohort of the Japan Environment and Children's study.
  Hiroyoshi Iwata; Sumitaka Kobayashi; Mariko Itoh; Sachiko Itoh; Rahel Mesfin Ketema; Naomi Tamura; Chihiro Miyashita; Takeshi Yamaguchi; Keiko Yamazaki; Hideyuki Masuda; Yu Ait Bamai; Yasuaki Saijo; Yoshiya Ito; Shoji F Nakayama; Michihiro Kamijima; Reiko Kishi
  Environment international, 183, 108321, 108321, 2023年11月11日, ［国際誌］
  英語, 研究論文（学術雑誌）, Kawasaki disease (KD) is common among pediatric patients and is associated with an increased risk of later cardiovascular complications, though the precise pathophysiology of KD remains unknown. Per- and polyfluoroalkyl substances (PFAS) have gathered notoriety as the causal pathogens of numerous diseases as well as for their immunosuppressive effects. The present epidemiological study aims to assess whether PFAS may affect KD risk. We evaluated research participants included in the ongoing prospective nationwide birth cohort of the Japan Environment and Children's Study (JECS). Among the over 100,000 pregnant women enrolled in the JECS study, 28 types of PFAS were measured in pregnancy in a subset of participants (N = 25,040). The JECS followed their children born between 2011 and 2014 (n total infants = 25,256; n Kawasaki disease infants = 271), up to age four. Among the 28 types of PFAS, those which were detected in >60 % of participants at levels above the method reporting limit (MRL) were eligible for analyses. Multivariable logistic regressions were implemented on the seven eligible PFAS, adjusting for multiple comparison effects. Finally, we conducted Weighted Quantile Sum (WQS) and Bayesian kernel machine regression (BKMR) to assess the effects of the PFAS mixture on KD. Therefore, we ran the BKMR model using kernel mechanical regression equations to examine PFAS exposure and the outcomes of KD. Upon analysis, the adjusted multivariable regression results did not reach statistical significance for the seven eligible substances on KD, while odds ratios were all under 1.0. WQS regression was used to estimate the mixture effect of the seven eligible PFAS, revealing a negative correlation with KD incidence; similarly, BKMR implied an inverse association between the PFAS mixture effect and KD incidence. In conclusion, PFAS exposure was not associated with increased KD incidence.
• 研究プロトコール発表 北海道の小学校6年生におけるエキノコックス症抗体保有率の調査
  岩田 啓芳; 山口 健史; 田村 菜穂美; 山本 理恵子; 東條 真希; 伊藤 真利子; 山崎 圭子; 宮下 ちひろ; 伊藤 佐智子; Ketema Rahel; 池田 敦子; 村林 宏; 伊藤 善也; 野中 成晃; 岸 玲子
  北海道公衆衛生学雑誌, 37, 1特別付録, 44, 44, 北海道公衆衛生学会, 2023年11月
  日本語
• 妊婦のカフェイン摂取量と生後12ヵ月までの子どもの発達との関連 環境省エコチル調査
  西原 進吉; 小林 澄貴; 伊藤 真利子; 西條 泰明; 伊藤 善也; 岸 玲子
  日本公衆衛生学会総会抄録集, 82回, 264, 264, 日本公衆衛生学会, 2023年10月
  日本語
• 成人期のPTSDと小児期の虐待歴における視床下部-下垂体-副腎系とレニン-アンジオテンシン-アルドステロン系(Hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system in adulthood PTSD and childhood maltreatment history)
  筧 亮子; 堀 弘明; 吉田 冬子; 伊藤 真利子; 林 明明; 丹羽 まどか; 成田 恵; 井野 敬子; 今井 理紗; 篠山 大明; 加茂 登志子; 功刀 浩; 金 吉晴
  国立精神・神経医療研究センター精神保健研究所年報, 36, 204, 204, (国研)国立精神・神経医療研究センター精神保健研究所, 2023年07月
  日本語
• Hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system in adulthood PTSD and childhood maltreatment history(タイトル和訳中)
  筧 亮子; 堀 弘明; 吉田 冬子; 伊藤 真利子; 林 明明; 丹羽 まどか; 成田 恵; 井野 敬子; 今井 理紗; 篠山 大明; 加茂 登志子; 功刀 浩; 金 吉晴
  国立精神・神経医療研究センター精神保健研究所年報, 36, 204, 204, (国研)国立精神・神経医療研究センター精神保健研究所, 2023年07月
  日本語
• Suicidality in civilian women with PTSD: Possible link to childhood maltreatment, proinflammatory molecules, and their genetic variations
  Hitomi Kawanishi; Hiroaki Hori; Fuyuko Yoshida; Mariko Itoh; Mingming Lin; Madoka Niwa; Megumi Narita; Takeshi Otsuka; Keiko Ino; Risa Imai; Shin Fukudo; Toshiko Kamo; Hiroshi Kunugi; Yoshiharu Kim
  Brain, Behavior, & Immunity - Health, 30, 100650, 100650, Elsevier BV, 2023年07月, ［査読有り］
  研究論文（学術雑誌）
• 妊婦の母体血中水銀・セレン濃度と4歳までの児の神経発達との関連 エコチル調査
  小林 澄貴; 伊藤 佐智子; 宮下 ちひろ; アイツバマイ ゆふ; 山口 健史; 増田 秀幸; 伊藤 真利子; 山崎 圭子; 田村 菜穂美; ハンリー・シャロン; 池田 敦子; 西條 泰明; 伊藤 善也; 岸 玲子
  日本衛生学雑誌, 78, Suppl., S173, S173, (一社)日本衛生学会, 2023年03月
  日本語
• Validation of childhood trauma questionnaire-short form in Japanese clinical and nonclinical adults
  Miho Nakajima; Hiroaki Hori; Mariko Itoh; Mingming Lin; Hitomi Kawanishi; Megumi Narita; Yoshiharu Kim
  Psychiatry Research Communications, 2, 3, 100065, 100065, Elsevier BV, 2022年09月, ［査読有り］
  研究論文（学術雑誌）
• Impact of prenatal exposure to mercury and selenium on neurodevelopmental delay in children in the Japan Environment and Children’s Study using the ASQ-3 questionnaire: a prospective birth cohort
  Sumitaka Kobayashi; Sachiko Itoh; Chihiro Miyashita; Yu Ait Bamai; Takeshi Yamaguchi; Hideyuki Masuda; Mariko Itoh; Keiko Yamazaki; Naomi Tamura; Sharon J.B. Hanley; Atsuko Ikeda-Araki; Yasuaki Saijo; Yoshiya Ito; Miyuki Iwai-Shimada; Shin Yamazaki; Michihiro Kamijima; Reiko Kishi
  Environment International, 107448, 107448, Elsevier BV, 2022年08月, ［査読有り］
  研究論文（学術雑誌）
• Association between maternal caffeine intake during pregnancy and child development at 6 and 12 months: The Japan Environment and Children's Study
  Shinkichi Nishihara; Sumitaka Kobayashi; Atsuko Ikeda-Araki; Chihiro Miyashita; Sachiko Itoh; Keiko Yamazaki; Yu Ait Bamai; Naomi Tamura; Hideyuki Masuda; Mariko Itoh; Yasuaki Saijo; Yoshiya Ito; Reiko Kishi
  Early Human Development, 105607, 105607, Elsevier BV, 2022年06月, ［査読有り］
  研究論文（学術雑誌）
• 恐怖記憶の分子・生理学的基盤の解明とPTSDの治療開発 PTSD治療におけるmemantineの効果と意義
  金 吉晴; 堀 弘明; 伊藤 真利子; 松井 三枝; 加茂 登志子; 斎藤 卓弥; 西松 能子; 鬼頭 諭; 喜田 聡
  精神神経学雑誌, 124, 4付録, S, 295, (公社)日本精神神経学会, 2022年04月
  日本語
• Hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system in adulthood PTSD and childhood maltreatment history.
  Ryoko Kakehi; Hiroaki Hori; Fuyuko Yoshida; Mariko Itoh; Mingming Lin; Madoka Niwa; Megumi Narita; Keiko Ino; Risa Imai; Daimei Sasayama; Toshiko Kamo; Hiroshi Kunugi; Yoshiharu Kim
  Frontiers in psychiatry, 13, 967779, 967779, 2022年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Accumulated evidence shows that psychological trauma and posttraumatic stress disorder (PTSD) are associated with dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis. Besides the HPA axis hormones, recent evidence suggests that the renin-angiotensin-aldosterone (RAA) system and genetic factors may be involved in trauma/PTSD as well as in HPA axis regulation. This study attempted to better understand the HPA axis function in relation to PTSD and childhood maltreatment by simultaneously examining RAA system and genetic polymorphisms of candidate genes. Here we studied 69 civilian women with PTSD and 107 healthy control women without DSM-IV-based traumatic experience. Childhood maltreatment history was assessed with the Childhood Trauma Questionnaire. PTSD severity was assessed with the Posttraumatic Diagnostic Scale. Functional disability was assessed with the Sheehan Disability Scale. HPA axis was examined by measuring blood levels of cortisol, adrenocorticotropic hormone, and dehydroepiandrosterone-sulphate (DHEA-S). RAA system was examined by measuring blood renin and aldosterone levels. The FKBP5 rs1360780 and CACNA1C rs1006737 polymorphisms were genotyped. No significant differences were seen between patients and controls in any of the five hormone levels. DHEA-S levels were significantly negatively correlated with overall PTSD severity (p = 0.003) and functional disability (p = 0.008). A two-way analysis of variance with diagnostic groups and genotypes as fixed factors revealed that patients with the rs1006737 A-allele had significantly lower DHEA-S levels than patients with the GG genotype (p = 0.002) and controls with the A-allele (p = 0.006). Childhood maltreatment history was not significantly correlated with any of the five hormone levels. These results were generally unchanged after controlling for the potentially confounding effect of age, depression, and anxiety. Our findings suggest that lower DHEA-S levels could indicate more severe subtype of PTSD, the association of which might be partly modified by the CACNA1C polymorphism.
• Hypertensive Disorders during Pregnancy and Anthropometric Measurement of Children up to 7 Years of Age: The Hokkaido Birth Cohort Study in Japan.
  Kritika Poudel; Sumitaka Kobayashi; Chihiro Miyashita; Takeshi Yamaguchi; Naomi Tamura; Atsuko Ikeda-Araki; Yu Ait Bamai; Sachiko Itoh; Keiko Yamazaki; Hideyuki Masuda; Mariko Itoh; Reiko Kishi
  International journal of environmental research and public health, 18, 20, 2021年10月18日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Hypertensive disorders during pregnancy (HDP) increase the risk of offspring with a low birth weight, preterm birth and small-for-gestational age; however, evidence of the anthropometric measurements during early childhood remains limited. We aimed to understand the associations between maternal HDP and anthropometric measurements of children aged up to seven years in a Japanese cohort. In total, 20,926 mother-infant pairs participated in the Hokkaido Study on Environment and Children's Health, Japan, from 2002 to 2013. Medical reports were used to confirm HDP exposure, while weight, height, height z score, and weight z score were the outcomes. The prevalence of HDP in the study population was 1.7%. The birth height of male children born to HDP mothers was smaller as compared to those born to non-HDP mothers. When adjusted with covariates, the linear regressions showed significant changes in birth weight (β: -79.3; 95% confidence interval [CI]: -154.8, -3.8), birth height (-0.67; 95% CI: -1.07, -0.26), weight at seven years (1.21; 95% CI: 0.13, 2.29), and weight gain between four and seven years (1.12; 95% CI: 0.28, 1.96) of male children exposed to HDP. Differences were more significant in male children than female. Our study showed that despite low birth weight, male children exposed to HDP caught up with their growth and gained more weight by seven years of age compared with male children not exposed to HDP, whereas no such differences were observed in female children; however, this finding requires replication.
• Association between the Concentrations of Metallic Elements in Maternal Blood during Pregnancy and Prevalence of Abdominal Congenital Malformations: The Japan Environment and Children's Study.
  Chihiro Miyashita; Yasuaki Saijo; Yoshiya Ito; Atsuko Ikeda-Araki; Sachiko Itoh; Keiko Yamazaki; Sumitaka Kobayashi; Yu Ait Bamai; Hideyuki Masuda; Naomi Tamura; Mariko Itoh; Takeshi Yamaguchi; Shin Yamazaki; Reiko Kishi; The Japan Environment And Children's Study Group
  International journal of environmental research and public health, 18, 19, 2021年09月26日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Abdominal congenital malformations are responsible for early mortality, inadequate nutrient intake, and infant biological dysfunction. Exposure to metallic elements in utero is reported to be toxic and negatively impacts ontogeny. However, no prior study has sufficiently evaluated the effects of exposure to metallic elements in utero on abdominal congenital malformations. The aim of the present study was to evaluate associations between metallic elements detected in maternal blood during pregnancy and congenital abdominal malformations. Data from participants in the Japan Environment and Children's Study was used in the present study, and contained information on singleton and live birth infants without congenital abnormalities (control: n = 89,134) and abdominal malformations (case: n = 139). Heavy metals such as mercury (Hg), lead (Pb), cadmium (Cd), and trace elements of manganese (Mn) and selenium (Se) were detected in maternal serum samples during mid- and late-gestation. Infant congenital abnormalities were identified from delivery records at birth or one month after birth by medical doctors. In a multivariate analysis adjusted to account for potential confounders, quartiles of heavy metals and trace elements present in maternal blood were not statistically correlated to the prevalence of abdominal congenital malformations at birth. This study is the first to reveal the absence of significant associations between exposure levels to maternal heavy metals and trace elements in utero and the prevalence of abdominal congenital malformations in a large cohort of the Japanese population. Further studies are necessary to investigate the impact of exposure to heavy metals and trace elements via maternal blood in offspring after birth.
• Hokkaido birth cohort study on environment and children's health: cohort profile 2021.
  Reiko Kishi; Atsuko Ikeda-Araki; Chihiro Miyashita; Sachiko Itoh; Sumitaka Kobayashi; Yu Ait Bamai; Keiko Yamazaki; Naomi Tamura; Machiko Minatoya; Rahel Mesfin Ketema; Kritika Poudel; Ryu Miura; Hideyuki Masuda; Mariko Itoh; Takeshi Yamaguchi; Hisanori Fukunaga; Kumiko Ito; Houman Goudarzi
  Environmental health and preventive medicine, 26, 1, 59, 59, 2021年05月22日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.
• Hypertensive Disorders during Pregnancy (HDP), Maternal Characteristics, and Birth Outcomes among Japanese Women: A Hokkaido Study.
  Kritika Poudel; Sumitaka Kobayashi; Chihiro Miyashita; Atsuko Ikeda-Araki; Naomi Tamura; Yu Ait Bamai; Sachiko Itoh; Keiko Yamazaki; Hideyuki Masuda; Mariko Itoh; Kumiko Ito; Reiko Kishi
  International journal of environmental research and public health, 18, 7, 2021年03月24日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Hypertension during pregnancy causes a greater risk of adverse birth outcomes worldwide; however, formal evidence of hypertensive disorders during pregnancy (HDP) in Japan is limited. We aimed to understand the association between maternal characteristics, HDP, and birth outcomes. In total, 18,833 mother-infant pairs were enrolled in the Hokkaido study on environment and children's health, Japan, from 2002 to 2013. Medical records were used to identify hypertensive disorders and birth outcomes, namely, small for gestational age (SGA), SGA at full term (term-SGA), preterm birth (PTB), and low birth weight (LBW). The prevalence of HDP was 1.9%. Similarly, the prevalence of SGA, term-SGA, PTB, and LBW were 7.1%, 6.3%, 7.4%, and 10.3%, respectively. The mothers with HDP had increased odds of giving birth to babies with SGA (2.13; 95% Confidence Interval (CI): 1.57, 2.88), PTB (3.48; 95%CI: 2.68, 4.50), LBW (3.57; 95%CI: 2.83, 4.51) than normotensive pregnancy. Elderly pregnancy, low and high body mass index, active and passive smoking exposure, and alcohol consumption were risk factors for different birth outcomes. Therefore, it is crucial for women of reproductive age and their families to be made aware of these risk factors through physician visits, health education, and various community-based health interventions.
• Childhood maltreatment history and attention bias variability in healthy adult women: role of inflammation and the BDNF Val66Met genotype.
  Hiroaki Hori; Mariko Itoh; Mingming Lin; Fuyuko Yoshida; Madoka Niwa; Yuko Hakamata; Mie Matsui; Hiroshi Kunugi; Yoshiharu Kim
  Translational psychiatry, 11, 1, 122, 122, 2021年02月11日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Childhood maltreatment has been associated with greater attention bias to emotional information, but the findings are controversial. Recently, a novel index of attention bias, i.e., attention bias variability (ABV), has been developed to better capture trauma-related attentional dysfunction. However, ABV in relation to childhood trauma has not been studied. Here, we examined the association of childhood maltreatment history with attention bias/ABV in 128 healthy adult women. Different types of childhood maltreatment were assessed with the Childhood Trauma Questionnaire. Attention bias/ABV was measured by the dot-probe task. Possible mechanisms whereby childhood maltreatment affects attention bias/ABV were also explored, focusing on blood proinflammatory markers and the BDNF Val66Met polymorphism. We observed a significant positive correlation between childhood emotional abuse and ABV (P = 0.002). Serum high-sensitivity tumor necrosis factor-α levels were significantly positively correlated with ABV (P < 0.001), but not with childhood maltreatment. Jonckheere-Terpstra trend test showed a significant tendency toward greater ABV with increasing numbers of the BDNF Met alleles (P = 0.021). A two-way analysis of variance further revealed that the genotype-by-emotional abuse interaction for ABV was significant (P = 0.022); individuals with the Val/Met and Met/Met genotypes exhibited even greater ABV when childhood emotional abuse was present. These results indicate that childhood emotional abuse can have a long-term negative impact on emotional attention control. Increased inflammation may be involved in the mechanism of ABV, possibly independently of childhood maltreatment. The BDNF Met allele may dose-dependently increase ABV by interacting with childhood emotional abuse.
• Association of CRP genetic variation with symptomatology, cognitive function, and circulating proinflammatory markers in civilian women with PTSD.
  Takeshi Otsuka; Hiroaki Hori; Fuyuko Yoshida; Mariko Itoh; Mingming Lin; Madoka Niwa; Keiko Ino; Risa Imai; Sei Ogawa; Mie Matsui; Toshiko Kamo; Hiroshi Kunugi; Yoshiharu Kim
  Journal of affective disorders, 279, 640, 649, 2021年01月15日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with increased inflammation. C-reactive protein (CRP) is a marker of systemic inflammation, and recently, single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with increased blood CRP protein levels and illness severity in PTSD patients. However, the mechanism by which the CRP SNPs are involved in PTSD remains unclear. Here we investigated the association of CRP genetic variation with blood proinflammatory protein levels, symptomatology, and cognitive function, and further explored the moderating effect of childhood maltreatment history, in adult patients with PTSD. METHODS: Fifty-seven Japanese civilian women with PTSD and 73 healthy control women were enrolled. Three SNPs in the CRP gene, namely rs2794520, rs1130864, and rs3093059, were genotyped, and analyses focused on rs2794520 (T/C). Serum levels of high-sensitivity CRP (hsCRP), high-sensitivity tumor necrosis factor-α (hsTNF-α), and interleukin-6 were measured. PTSD symptoms were evaluated by the Posttraumatic Diagnostic Scale. Cognitive function was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status. Childhood maltreatment history was assessed by the Childhood Trauma Questionnaire. RESULTS: Patients with the rs2794520 CC/CT genotype, compared to those with the TT genotype, showed significantly higher levels of hsCRP (p=0.009) and hsTNF-α (p=0.001), more severe PTSD symptoms (p=0.036), and poorer cognitive function (p=0.018). A two-way analysis of variance revealed a significant genotype-by-maltreatment interaction for more severe PTSD avoidance symptom (p=0.012). LIMITATIONS: The relatively small sample size limited our findings. CONCLUSIONS: These findings may provide an insight into the etiology of PTSD from the inflammatory perspective.
• The efficacy of memantine in the treatment of civilian posttraumatic stress disorder: an open-label trial
  Hiroaki Hori; Mariko Itoh; Mie Matsui; Toshiko Kamo; Takuya Saito; Yoshiko Nishimatsu; Satoshi Kito; Satoshi Kida; Yoshiharu Kim
  European Journal of Psychotraumatology, 12, 1, 1859821, 1859821, Informa UK Limited, 2021年01月01日, ［査読有り］
  研究論文（学術雑誌）
• The BDNF Val66Met polymorphism affects negative memory bias in civilian women with PTSD.
  Hiroaki Hori; Mariko Itoh; Fuyuko Yoshida; Mingming Lin; Madoka Niwa; Yuko Hakamata; Keiko Ino; Risa Imai; Sei Ogawa; Mie Matsui; Toshiko Kamo; Hiroshi Kunugi; Yoshiharu Kim
  Scientific reports, 10, 1, 3151, 3151, 2020年02月21日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Memory abnormalities are considered a core feature of posttraumatic stress disorder (PTSD). Studies attempting to quantify such memory dysfunction in PTSD have reported that individuals with this disorder exhibit selective memory bias toward negative material. The low expression Met allele of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with the aetiology of PTSD and with memory abnormalities. It is therefore possible that the BDNF Val66Met polymorphism can moderate the relationship between PTSD and memory bias. Here we examined this association in 50 civilian women with PTSD and 70 non-trauma-exposed healthy control women. All subjects were genotyped for the BDNF Val66Met (rs6265) polymorphism. Negative memory bias was assessed using a recognition memory task. Patients showed significantly greater negative memory bias compared to controls. In patients, negative memory bias significantly increased with increasing numbers of Met alleles; while no significant relationship was seen in controls. Further pairwise analyses revealed that patients with the Met allele had significantly greater negative memory bias than controls. These results suggest that the relationship between PTSD and negative memory bias can be moderated by the BDNF Val66Met polymorphism. More studies are needed to further clarify the relationship between this polymorphism and memory abnormalities in PTSD.
• Possible Long-Term Effects of Childhood Maltreatment on Cognitive Function in Adult Women With Posttraumatic Stress Disorder.
  Michi Nakayama; Hiroaki Hori; Mariko Itoh; Mingming Lin; Madoka Niwa; Keiko Ino; Risa Imai; Sei Ogawa; Atsushi Sekiguchi; Mie Matsui; Hiroshi Kunugi; Yoshiharu Kim
  Frontiers in psychiatry, 11, 344, 344, 2020年, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Accumulated evidence shows that individuals with posttraumatic stress disorder (PTSD) have compromised cognitive function. PTSD is associated with childhood maltreatment, which also can negatively affect cognitive function. It is therefore possible that cognitive dysfunction in adult patients with PTSD can be due at least partly to childhood maltreatment, although little is documented on this issue. Here we aimed to examine the possible effect of childhood maltreatment on cognitive function in adult patients with PTSD. A total of 50 women with DSM-IV PTSD and 94 healthy control women were enrolled. Most of the patients developed PTSD after experiencing interpersonal violence during adulthood. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Compared to controls, patients reported significantly more experiences of all types of childhood maltreatment as assessed by the CTQ and showed significantly poorer performance on immediate memory, language, attention, and the total score of RBANS. In patients, sexual abuse scores were significantly negatively correlated with RBANS language (p < 0.001) and total score (p = 0.005). Further analyses revealed that PTSD patients with childhood sexual abuse had even poorer cognitive function than those without the abuse. In controls, no significant correlation was found between CTQ and RBANS scores. These results suggest that childhood maltreatment, specifically sexual abuse, may lead to persistent cognitive impairment in individuals with PTSD. Our findings might underscore the importance of early detection and intervention of childhood maltreatment, which will be achieved by careful observation of, and listening to, maltreated children in education and welfare scenes as well as clinical settings.
• ストレス関連疾患の疾患横断的なバイオマーカー検索のための脳MRI研究
  関口 敦; 伊藤 真利子; 林 明明; 伊藤 まどか; 堀 弘明; 菅原 彩子; 金 吉晴
  心身医学, 59, 8, 766, 766, (一社)日本心身医学会, 2019年12月, ［査読有り］
  日本語
• Relationships of blood proinflammatory markers with psychological resilience and quality of life in civilian women with posttraumatic stress disorder.
  Risa Imai; Hiroaki Hori; Mariko Itoh; Mingming Lin; Madoka Niwa; Keiko Ino; Sei Ogawa; Atsushi Sekiguchi; Hiroshi Kunugi; Tatsuo Akechi; Toshiko Kamo; Yoshiharu Kim
  Scientific reports, 9, 1, 17905, 17905, 2019年11月29日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Individuals with posttraumatic stress disorder (PTSD) show low resilience and impaired quality of life (QOL). Accumulating evidence shows that PTSD is associated with increased inflammation. Studies suggest that inflammation can be a key mechanism underlying low resilience/QOL, but this relationship has been understudied in individuals with PTSD. Here, we investigated the association of blood proinflammatory markers with self-reported resilience and QOL in civilian women with PTSD. Fifty-six women with PTSD and 73 healthy control women participated in this study. Resilience was assessed using the Connor-Davidson Resilience Scale. QOL was assessed using the World Health Organization Quality of Life-BREF. Blood samples were collected for the measurement of three proinflammatory markers including interleukin-6 (IL-6), high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Compared to controls, patients showed significantly higher IL-6 levels and lower resilience and QOL. In patients, IL-6 levels were significantly negatively correlated with resilience, and hsCRP levels were significantly negatively correlated with psychological QOL. These results show that increased levels of proinflammatory markers including IL-6 and hsCRP are associated with lower psychological resilience and QOL in PTSD patients. Our findings suggest that interventions and treatments targeting inflammation may aid in the recovery from PTSD and lead to better prognosis.
• Proinflammatory status-stratified blood transcriptome profiling of civilian women with PTSD.
  Hori H; Yoshida F; Itoh M; Lin M; Niwa M; Ino K; Imai R; Ogawa S; Matsui M; Kamo T; Kunugi H; Kim Y
  Psychoneuroendocrinology, 111, 104491, 104491, 2019年10月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Etiology of posttraumatic stress disorder (PTSD) remains largely unknown. Studies have shown that a significant subset of patients with PTSD exhibit increased inflammation, suggesting that the understanding of this disorder could be facilitated by classifying these patients by inflammatory status. Here we performed a microarray-based blood transcriptome analysis on proinflammatory status-stratified Japanese civilian women with PTSD most of whom developed the disorder after experiencing interpersonal violence. By utilizing our previously identified cut-off serum interleukin-6 (IL-6) level that approximately corresponded to the median IL-6 level of our PTSD patients, we classified patients into those with high IL-6 levels and those with normal IL-6 levels (n = 16 for each). Transcriptome profiles of these 2 groups were compared with the profile of 16 age-matched healthy control women. Differentially expressed genes between high IL-6 patients and controls showed significant enrichment in a number of gene ontology terms and pathways primarily involved in immune/inflammatory responses, and their protein-protein interaction network was significantly enriched. In contrast, differentially expressed genes between normal IL-6 patients and controls showed significant enrichment in several gene ontology terms related to ion transport and neural function. The microarray data were confirmed by reverse transcription quantitative PCR. These findings illustrate the heterogeneous molecular mechanisms of PTSD within this relatively homogeneous sample in terms of sex, trauma type, and ethnicity, suggesting that peripheral proinflammatory status such as IL-6 levels could be a useful subtyping marker for this disorder. With further research, it is hoped that our findings will be translated into personalized medicine.
• Memory bias and its association with memory function in women with posttraumatic stress disorder.
  Itoh M; Hori H; Lin M; Niwa M; Ino K; Imai R; Ogawa S; Matsui M; Kamo T; Kim Y
  Journal of affective disorders, 245, 461, 467, 2018年11月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Memory abnormalities are among a central feature of posttraumatic stress disorder (PTSD). It is suggested that individuals with PTSD exhibit memory bias; while evidence shows poor memory function in these individuals. We aimed to examine memory bias in PTSD patients relative to controls and to explore an association between memory bias and memory function. METHODS: Forty-six women with DSM-IV PTSD, most of whom developed the disorder after interpersonal violence, and 68 non-trauma-exposed healthy control women were studied. Memory bias was assessed by a recognition memory task using negative, neutral, and positive words. Memory function was assessed by a standardized neuropsychological test battery. Depression and anxiety symptoms were assessed by self-report measures. RESULTS: Compared to controls, patients showed significantly greater negative bias scores (i.e., correctly recognized rates for negative words minus those for neutral words) and poorer memory function. Negative bias scores were significantly correlated with worse memory function in patients. When patients were divided into those with lower vs. normal memory function, the former patients had significantly greater negative bias than the latter patients and controls. Memory bias scores in patients were not significantly correlated with depression or anxiety symptoms, nor were they significantly different between patients with comorbid major depressive disorder and those without. LIMITATIONS: The cross-sectional design and absence of the trauma-exposed non-PTSD group limited our findings. CONCLUSIONS: PTSD patients have greater negative memory bias, which can be associated with poorer memory function. Our findings may provide an insight into the nature of memory abnormalities in PTSD.
• Cognitive function in Japanese women with posttraumatic stress disorder: Association with exercise habits.
  Ryoko Narita-Ohtaki; Hiroaki Hori; Mariko Itoh; Mingming Lin; Madoka Niwa; Keiko Ino; Risa Imai; Sei Ogawa; Atsushi Sekiguchi; Mie Matsui; Hiroshi Kunugi; Toshiko Kamo; Yoshiharu Kim
  Journal of affective disorders, 236, 306, 312, 2018年08月15日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with cognitive impairments, yet little is documented on the cognitive function of PTSD patients in Asian countries. It is shown that regular exercise can reduce PTSD symptoms, while no study has investigated the association between exercise and cognition in PTSD patients. This study aimed to examine cognitive functions of Japanese women with PTSD, and to explore the association between regular exercise and cognitive functions. METHODS: Forty-two women with DSM-IV PTSD and 66 demographically matched healthy control women participated in this study. Most of the patients developed PTSD after experiencing interpersonal violence. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regular exercise habit was assessed by a self-reported questionnaire. RESULTS: Compared to controls, PTSD patients performed significantly more poorly in all cognitive domains examined, including immediate memory, visuospatial construction, language, attention, delayed memory, as well as the total score of RBANS (all p < 0.001). Compared to PTSD patients without the habit of exercise, those who habitually exercised showed significantly better performance on delayed memory (p = 0.006), which survived after controlling for potentially confounding variables in a multiple regression model. LIMITATIONS: The cross-sectional design and relatively small sample size limited our findings. CONCLUSIONS: PTSD in Japanese women is associated with pervasively impaired cognitive functions, including notable impairments in verbal memory. Such memory deficits might be improved by regular exercise, although further studies are needed to investigate the causal relationship between exercise and cognition in PTSD.
• Inflammatory markers and their possible effects on cognitive function in women with posttraumatic stress disorder.
  Risa Imai; Hiroaki Hori; Mariko Itoh; Mingming Lin; Madoka Niwa; Keiko Ino; Sei Ogawa; Makiko Ishida; Atsushi Sekiguchi; Mie Matsui; Hiroshi Kunugi; Tatsuo Akechi; Toshiko Kamo; Yoshiharu Kim
  Journal of psychiatric research, 102, 192, 200, 2018年07月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Posttraumatic stress disorder (PTSD) has been associated with increased inflammation, albeit with some controversy. Another key feature of PTSD is compromised function in wide-ranging cognitive domains. Increased peripheral inflammation can contribute to cognitive dysfunction, although this relationship has not been studied in patients with PTSD. Here, we examined blood inflammatory markers in adult patients with PTSD compared to healthy controls taking account of potentially confounding effects of childhood maltreatment and comorbid major depressive disorder (MDD), and explored the association between inflammation and cognition. We enrolled 40 women with PTSD, most of whom developed the disorder after interpersonal violence during adulthood, and 65 healthy control women. Diagnoses were made based on DSM-IV. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Blood samples were collected for the measurement of 5 inflammatory markers including interleukin-6 (IL-6), soluble IL-6 receptor, interleukin-1β, high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein. Compared to controls, patients with PTSD showed significantly higher IL-6 levels (p = 0.009) and lower scores on all RBANS domains (all p < 0.01). IL-6 levels in patients were not significantly associated with the presence/absence of comorbid MDD or CTQ scores. IL-6 levels in patients were significantly negatively correlated with RBANS visuospatial construction (p = 0.046), language (p = 0.008), attention (p = 0.036) and total score (p = 0.008). These results suggest that elevated IL-6 is associated with PTSD and that the lower cognitive function in PTSD may be due at least partly to increased inflammation.
• A new short version of the Posttraumatic Diagnostic Scale: validity among Japanese adults with and without PTSD
  Mariko Itoh; Yuri Ujiie; Nobukazu Nagae; Madoka Niwa; Toshiko Kamo; Mingming Lin; Sayuri Hirohata; Yoshiharu Kim
  EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY, 8, 1, 1364119, 2017年08月, ［査読有り］
  英語, 研究論文（学術雑誌）
• The Japanese version of the Posttraumatic Diagnostic Scale: Validity in participants with and without traumatic experiences.
  Mariko Itoh; Yuri Ujiie; Nobukazu Nagae; Madoka Niwa; Toshiko Kamo; Mingming Lin; Sayuri Hirohata; Yoshiharu Kim
  Asian journal of psychiatry, 25, 1, 5, 2017年02月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The Posttraumatic Diagnostic Scale (PDS) is a brief, self-report questionnaire developed for the diagnostic screening and assessment of the severity of posttraumatic stress disorder (PTSD); the PDS is based on the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (4th edition; DSM-IV). We investigated the validity and reliability of the Japanese version of the PDS in a clinical (n=109) and a non-clinical (n=116) sample, recruited from an outpatient psychiatric facility and a university student population, respectively. The Japanese versions of the PDS and the Clinician-Administered PTSD Scale (CAPS/DSM-IV) were administered to the participants. The Japanese PDS's diagnostic sensitivity and specificity exceeded 90%. The correlation between the severity scores assessed by the Japanese PDS and the CAPS was also high (r=0.92). The findings suggest that the Japanese version of the PDS is useful for diagnostically screening PTSD and assessing symptom severity.
• Reliability and validity of a self-report emotional expressivity measure: The Japanese version of the Berkeley Expressivity Questionnaire
  Mingming Lin; Sayaka Soi-Kawase; Ryoko Narita-Ohtaki; Mariko Itoh; Yoshiharu Kim
  JAPAN JOURNAL OF NURSING SCIENCE, 13, 1, 196, 201, 2016年01月, ［査読有り］
  英語, 研究論文（学術雑誌）
• 比較と処理の水準が再生に及ぼす影響
  伊藤 真利子; 綾部 早穂
  認知心理学研究, 10, 2, 175, 182, 日本認知心理学会, 2013年, ［査読有り］, ［国内誌］
  日本語, 記銘項目が実験者によって割り当てられる場合よりも，実験参加者自身により選択される場合のほうが記憶保持は優れる．この自己選択効果の生起には，選択肢項目間の相対比較が必要である可能性が示唆されているが（伊藤・綾部・菊地，2012），相対比較の際に意味水準での特徴にアクセスすることが記憶を促した可能性は否定できない（処理水準効果）．本研究の偶発学習段階において実験参加者は，意味水準か非意味水準の特徴に基づいて二つの選択肢項目間の相対比較を行うか，単独の項目に対して意味水準か非意味水準で判断を行った．その結果，二つの項目間で相対比較が行われた場合にも，単独の項目に対して判断が行われた場合にも，再生成績における処理水準効果が認められた．さらに重要なことに，処理水準にはかかわらず項目間の相対比較による記憶の促進が認められた．よって，記憶における自己選択効果の生起には選択の際の相対比較が必要であり，処理水準効果のみが貢献しているとは言えない可能性が示唆された．
• 自己選択時の比較過程による記憶促進効果
  伊藤 真利子; 綾部 早穂; 菊地 正
  認知心理学研究, 10, 1, 37, 47, 日本認知心理学会, 2012年, ［査読有り］
  日本語, 記銘項目が実験者によって割り当てられる場合よりも，実験参加者自身により選択される場合のほうが記憶保持は優れる（自己選択効果）．本研究は，選択時における選択項目と非選択項目の両方を短期記憶に保持する過程が後の再生を促進するために必要十分であるのか，それとも短期記憶保持された選択肢間を比較する過程が必要であるかを検討した．実験1では，選択段階で選択項目のみを短期記憶に保持する強制選択条件，選択項目と非選択項目を保持する遅延選択条件，保持された選択肢間での比較を行う比較選択条件と自己選択条件を設けた．選択項目の再生率は前の2条件間では差がなかったが，後の2条件は前の2条件よりも有意に高かった．よって，選択時に短期記憶に保持された選択肢を互いに比較する過程が再生の促進に重要である可能性が示唆された．実験2では，意味的な基準での比較と非意味的な基準での比較による再生成績の違いが認められなかったことから，実験1の比較選択条件での再生の促進が意味処理のみで説明される可能性は低いと考えられた．
• 脅威刺激の検出優位性における形態特徴の重要性
  伊藤 真利子; 井上 和哉; 佐藤 和代; 菊地 正
  感情心理学研究, 18, 2, 96, 105, 日本感情心理学会, 2011年, ［査読有り］
  日本語, This study investigated whether the threat-superiority effect in a visual search task was based on the processing of shapes (lower level), or the processing of semantic characteristics (higher level). Participants were asked to determine whether all pictures in a visual search display were members of the same category (all distractors), or whether there was a discrepant member (the target). The threat-superiority effect was determined by a shorter reaction time for detecting threatening, than non-threatening targets. If the threat-superiority effect was based on semantic processing, it was expected that the effect would be observed even when a target and distractors shared a basic shape, such as a knife among combs, or a comb among knives. Experiment 1 showed a threat &ldquo;shape&rdquo;-superiority effect, but not a threat &ldquo;semantic&rdquo;-superiority effect. In Experiment 2, when the threatening target was a gun (Japanese participants have no direct experiences with guns, but know that guns are threatening), the threat-superiority effect was not found. These findings suggest that the threat-superiority effect is not based on semantic processing, but on processing of shape characteristics.

• PLASMA LIPID AND FATTY ACID CONCENTRATIONS IN PATIENTS WITH POSTTRAUMATIC STRESS DISORDER (PTSD) AND HEALTHY INDIVIDUALS: ASSOCIATIONS WITH DIAGNOSIS, SYMPTOMS, AND INFLAMMATORY MARKERS
  *Shintaro Ogawa; Hiroaki Hori; Madoka Niwa; Mariko Itoh; Mingming Lin; Fuyuko Yoshida; Keiko Ino; Hitomi Kawanishi; Megumi Narita; Wakako Nakano; Risa Imai; Mie Matsui; Toshiko Kamo; Hiroshi Kunugi; Yoshiharu Kim, International Journal of Neuropsychopharmacology, 2025年02月12日
  Abstract
  
  Background
  Posttraumatic stress disorder (PTSD) is a severe psychiatric condition resulting from a traumatic event, affecting both mental and physical health and impairing cognitive function. Lipid- related molecules, such as cholesterol and fatty acids, are crucial in the central nervous system (CNS), and their alterations can influence CNS functions related to PTSD symptoms. However, there is a scarcity of case-control studies examining the connection between plasma lipid-related molecules and PTSD.
  
  
  Aims & Objectives
  We aimed to delve into the link between lipid-related molecules and PTSD, exploring pathophysiology, inter-group variations, and their associations with background factors, psychological functions, PTSD symptoms, and plasma inflammation markers. Additionally, we aimed to assess the potential of lipid-related molecules for subject subtyping and investigate lipid profiles, psychological features, and symptomatic patterns using latent profile analysis (LPA).
  
  
  Method
  We examined 165 participants, comprising 67 PTSD patients and 98 healthy controls without trauma exposure. We assessed PTSD symptoms in patients using the DSM-IV version of the Posttraumatic Diagnostic Scale (PDS-IV). Childhood trauma was gauged through the Childhood Trauma Questionnaire (CTQ), and cognitive function was appraised using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) for all subjects. Venous blood was collected around noon, and plasma samples were analyzed for lipid-related molecules and inflammatory cytokine levels at SRL Inc (Tokyo, Japan). We considered a two-tailed P-value of &lt;0.01 as statistically significant in all analyses, except for LPA, where a significance level of P &lt;0.05 was employed due to its highly exploratory nature.
  
  
  Results
  PTSD patients exhibited significantly lower plasma HDL cholesterol and n-6 linoleic acid levels, as well as higher plasma saturated palmitic acid and Triene/Tetraene (T/T) ratio compared to healthy controls. Hyperarousal symptoms (PDS category D scores) in PTSD patients were significantly positively associated with plasma levels of γ-linolenic (P = 2.5E-5), dihomo-γ-linolenic, mead acids, and the T/T ratio. Plasma γ-linolenic acid levels also showed significant positive correlations with PDS total scores. CTQ scores were significantly negatively correlated with plasma LDL cholesterol levels. Cognitive function, as assessed by RBANS scores, had positive associations with docosahexaenoic acid, n-3 fatty acids, and linoleic acid, but negative associations with dihomo-γ-linolenic, palmitic, and saturated fatty acids. Inflammation-related plasma markers were significantly correlated with plasma oleic (P = 1.9E-5), palmitic, and n-9 fatty acids, while linoleic and polyunsaturated fatty acids displayed opposite correlations. LPA analysis identified variations in plasma lipid and fatty acid profiles, including high linolenic n-6 fatty acids, suitable for subtyping PTSD patients.
  
  
  Discussion & Conclusion
  This study underscores the importance of plasma lipid and fatty acid alterations in PTSD patients, potentially connected to pathophysiology and symptoms, providing a foundation for further research. Additionally, we have identified unique plasma lipid and fatty acid profiles for subtyping patients with PTSD.
  , 英語
• PTSD女性患者における自殺リスク 幼少期被虐待体験、炎症マーカー、炎症系遺伝子多型との関連
  河西 ひとみ; 堀 弘明; 吉田 冬子; 伊藤 真利子; 林 明明; 丹羽 まどか; 井野 敬子; 今井 理紗; 関口 敦; 加茂 登志子; 功刀 浩; 金 吉晴, 国立精神・神経医療研究センター精神保健研究所年報, 35, 195, 195, 2022年06月
  (国研)国立精神・神経医療研究センター精神保健研究所, 日本語
• PTSD治療におけるmemantineの効果と意義
  金吉晴; 堀弘明; 伊藤真利子; 松井三枝; 加茂登志子; 斎藤卓弥; 西松能子; 西松能子; 鬼頭諭; 喜田聡, 日本精神神経学会総会プログラム・抄録集, 118th, 2022年
• 妊娠中の喫煙曝露と児の注意欠如多動症との関連 北海道スタディ
  伊藤 真利子; 西原 進吉; 小林 澄貴; 須山 聡; 川手 菜未; 宮下 ちひろ; 岸 玲子, 日本公衆衛生学会総会抄録集, 80回, 379, 379, 2021年11月
  日本公衆衛生学会, 日本語
• 心的外傷後ストレス障害の評価指標としての認知バイアスの検討
  伊藤 真利子; 丹羽 まどか; 林 明明; 金 吉晴, メンタルヘルス岡本記念財団研究助成報告集, 32, 7, 11, 2021年03月
  PTSD(心的外傷後ストレス障害)患者における記憶のネガティブ・バイアス(ネガティブな情報は中立的な情報に比べて思い出されやすい)をトラウマのない健常統制群との比較から明らかにすることを目的に、18〜59歳の女性182名(PTSD患者群68名、トラウマ<主として性被害やドメスティックバイオレンス被害などの対人暴力被害>体験のない健常統制群114名)を対象に、ネガティブ語(「恐怖」など)、中立語(「台本」など)、ポジティブ語(「幸運」など)を用いた再認記憶課題(約25分)を行った。課題は、符号化段階、遅延段階、再認テスト段階により構成され、符号化段階で提示された語のうち、再認テスト段階で「あった」と正答できた語の割合(Hit率)における、ネガティブ語と中立語の差分をネガティブ・バイアスの指標とした。その結果、両群において、ネガティブ語のHit率は中立語のそれよりも高く、また、PTSD患者群のネガティブ・バイアスは健常統制群よりも有意に大きかった。, (公財)メンタルヘルス岡本記念財団, 日本語
• 炎症と記憶に着目したPTSDの遺伝学的検討
  堀弘明; 吉田冬子; 伊藤真利子; 林明明; 丹羽まどか; 井野敬子; 井野敬子; 今井理紗; 今井理紗; 小川成; 関口敦; 加茂登志子; 功刀浩; 金吉晴, 国立精神・神経医療研究センター精神保健研究所研究報告会プログラム・抄録集(Web), 32nd, 2021年
• 心的外傷後ストレス障害の評価指標としての認知バイアスの検討
  伊藤 真利子; 丹羽 まどか; 林 明明; 金 吉晴, メンタルヘルス岡本記念財団研究助成報告集, 31, 7, 12, 2020年03月
  記憶のネガティブ・バイアスについて検討し、PTSD症状、トラウマ的出来事に関する認知、対処行動、生活の質に関する質問紙調査を実施した。心的外傷ストレス障害(PTSD)患者群60名(平均年齢38.4歳)、健常統制群92名(平均年齢34.4歳)の152名の女性を対象とした。記憶のネガティブ・バイアスを評価するために、再認記憶課題を使用した。健常統制群は、PTSD患者群よりも有意に若く、教育水準には有意差はなかった。PTSD群では健常群と比較して生活の質が低く、不安や抑うつが有意に高く評価されていた。ネガティブ・バイアスについては、健常統制群よりもPTSD患者群において有意にバイアスの程度が大きいことが示された。PTSD重症度を表すPDSとの相関において、記憶のネガティブ・バイアスが大きいほど、PTSD全体重症度、とりわけ回避症状が有意に大きかった。記憶のネガティブ・バイアスはPTSD重症度、対処方略、生活の質の下位尺度の一部と関連していた。, (公財)メンタルヘルス岡本記念財団, 日本語
• 心的外傷後ストレス障害の女性患者における炎症マーカー
  今井理紗; 今井理紗; 堀弘明; 伊藤真利子; 林明明; 丹羽まどか; 井野敬子; 井野敬子; 小川成; 関口敦; 功刀浩; 明智龍男; 加茂登志子; 金吉晴, 国立精神・神経医療研究センター精神保健研究所研究報告会プログラム・抄録集(Web), 31st, 2020年
• 健常成人女性における幼少期トラウマと認知バイアスの関連
  伊藤真利子; 堀 弘明; 金 吉晴, 精神科臨床Legato, 5, 1, 29, 32, 2019年03月
  (株)メディカルレビュー社, 日本語
• PTSD女性患者における認知機能
  堀 弘明; 伊藤 真利子; 林 明明; 丹羽 まどか; 井野 敬子; 今井 理紗; 小川 成; 加茂 登志子; 金 吉晴, メンタルヘルス岡本記念財団研究助成報告集, 29, 101, 106, 2018年03月
  心的外傷後ストレス障害(PTSD)女性患者における認知機能について検討した。対象者はPTSD患者37名および健常対照者74名の計111名であり、年齢範囲は20〜64歳であった。JART(Japanese Adult Reading Test)得点を共変量とした共分散分析により、すべての指標においてPTSD群の成績が有意に低値であることが見出された。なかでも即時記憶、遅延記憶、総指標得点については1標準偏差(=15ポイント)以上の得点差がみられ、記憶の問題がとりわけ顕著であることが明らかになった。また、合併しているうつ病はPTSDの認知機能に有意な影響を及ぼさないこと、トラウマ曝露自体が認知機能に及ぼす影響は有意ではないことが示された。PTSD患者群において、PTSD重症度とRBANS(日本語版Repeatable Battery for the Assessment of Neuropsychological Status)各指標得点の相関を調べたところ、即時記憶、注意力、遅延記憶および総指標得点とPosttraumatic Stress Diagnostic Scale(PDS)合計得点の間に有意な負の相関が認められた。, (公財)メンタルヘルス岡本記念財団, 日本語
• 心的外傷後ストレス障害を有する日本人女性における認知機能:運動習慣との関連
  大滝涼子; 堀弘明; 伊藤真利子; 林明明; 丹羽まどか; 井野敬子; 今井理紗; 小川成; 関口敦; 松井三枝; 功刀浩; 加茂登志子; 金吉晴; 金吉晴, 国立精神・神経医療研究センター精神保健研究所研究報告会プログラム・抄録集(Web), 29th, 2018年
• PTSD診断・評価のためのPosttraumatic Diagnostic Scale日本語版および短縮版尺度の開発
  伊藤真利子; 氏家由里; 長江信和; 丹羽まどか; 加茂登志子; 林明明; 廣幡小百合; 金吉晴, 国立精神・神経医療研究センター精神保健研究所研究報告会プログラム・抄録集(Web), 29th, 2018年
• PTSD女性患者における認知機能
  堀 弘明; 伊藤 真利子; 林 明明; 丹羽 まどか; 井野 敬子; 今井 理紗; 小川 成; 関口 敦; 功刀 浩; 加茂 登志子; 金 吉晴, 国立精神・神経医療研究センター精神保健研究所年報, 30, 229, 229, 2017年10月
  (国研)国立精神・神経医療研究センター精神保健研究所, 日本語
• PTSD女性患者における炎症マーカー(Inflammatory markers in adult women with posttraumatic stress disorder)
  堀 弘明; 伊藤 真利子; 林 明明; 丹羽 まどか; 井野 敬子; 今井 理紗; 小川 成; 関口 敦; 功刀 浩; 加茂 登志子; 金 吉晴, 日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, 39回・47回, 175, 175, 2017年09月
  日本生物学的精神医学会・日本神経精神薬理学会, 英語
• PTSD女性患者における炎症マーカー(Inflammatory markers in adult women with posttraumatic stress disorder)
  堀 弘明; 伊藤 真利子; 林 明明; 丹羽 まどか; 井野 敬子; 今井 理紗; 小川 成; 関口 敦; 功刀 浩; 加茂 登志子; 金 吉晴, 日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集, 39回・47回, 175, 175, 2017年09月
  日本生物学的精神医学会・日本神経精神薬理学会, 英語
• 健常成人女性における幼少期トラウマと認知バイアスの関連
  伊藤 真利子; 林 明明; 丹羽 まどか; 堀 弘明; 金 吉晴, 日本心理学会大会発表論文集, 81回, 241, 241, 2017年08月
  (公社)日本心理学会, 日本語
• 健常成人における主観的不安と認知・生物学的指標の関連 PTSDの客観的診断指標開発に向けて
  伊藤 真利子; 丹羽 まどか; 林 明明; 大滝 涼子; 堀 弘明; 関口 敦; 金 吉晴, 国立精神・神経医療研究センター精神保健研究所年報, 29, 241, 241, 2016年10月
  (国研)国立精神・神経医療研究センター精神保健研究所, 日本語
• 運動習慣によるストレス反応の緩和 : 主観評価と自律神経活動評価による実験的検討
  伊藤 真利子; 林 明明; 金 吉晴, 若手研究者のための健康科学研究助成成果報告書 = Research-aid report, 31, 11, 16, 2016年04月
  明治安田厚生事業団, 日本語
• PTSDスクリーニングのための自記式尺度の開発:日本語版Posttraumatic Diagnostic Scaleの再体験3項目版尺度
  伊藤真利子; 氏家由里; 丹羽まどか; 丹羽まどか; 長江信和; 林明明; 林明明; 加茂登志子; 金吉晴, 日本トラウマティック・ストレス学会大会プログラム・抄録集, 15th, 2016年
• 成人精神保健研究部 日本語版感情表出尺度の信頼性および妥当性の検討
  林 明明; 河瀬 さやか; 伊藤 真利子; 大滝 涼子; 金 吉晴, 国立精神・神経医療研究センター精神保健研究所年報, 28, 253, 253, 2015年08月
  (国研)国立精神・神経医療研究センター精神保健研究所, 日本語
• PTSDの記憶機能と治療的意義
  伊藤 真利子; 金 吉晴, 精神保健研究 = Journal of mental health : official journal of the National Institute of Mental Health, NCNP, Japan, 27, 35, 39, 2014年
  国立精神・神経医療研究センター精神保健研究所, 日本語
• 日本語版PTSD診断尺度(PDS)の妥当性-臨床群における検討
  氏家由里; 伊藤真利子; 丹羽まどか; 長江信和; 林明明; 加茂登志子; 金吉晴, 日本トラウマティック・ストレス学会大会プログラム・抄録集, 13th, 2014年
• 大規模災害や犯罪被害者等による精神疾患の実態把握と対応ガイドラインの作成・評価に関する研究 唾液コルチゾール測定によるPTSD症状評価の利点と注意点:DV被害母子研究に向けて
  金吉晴; 伊藤真利子; 永岑光恵; 丹羽まどか; 加茂登志子, 大規模災害や犯罪被害者等による精神疾患の実態把握と対応ガイドラインの作成・評価に関する研究 平成25年度 総括・分担研究報告書, 2014年
• 記憶の自己選択効果に対する示差性処理説の検討:意味関連選択肢の反復による影響
  伊藤 真利子; 綾部 早穂, 認知心大会論文, 2013, 0, 84, 84, 2013年
  実験参加者自身によって選択された項目は実験者から指定された項目よりも思い出されやすい（自己選択効果）。自己選択条件においては、最終的に一つの項目を選択するために、比較の過程で選択肢の項目間の類似点と相違点が見出される（示差性処理）と推測される。本研究では、自己選択効果が示差性処理から説明されるかを検討した。自己選択条件の試行ブロック内で、意味関連語を共通の基準で繰り返し比較していく場合には、項目の示差性処理が効果的に行われにくくなると想定した。実験参加者は同じ意味カテゴリ内で繰り返して単語対のうち一方を選択していくように求められ、選択段階全体に占める自己選択条件の試行数が操作された。結果として、示差性処理による説明に一致して、自己選択条件の試行数が増えた場合に手がかり再生における自己選択効果が認められなくなった。, 日本認知心理学会
• 自己選択が項目間の記憶弁別に及ぼす効果
  伊藤 真利子; 岡戸 涼; 綾部 早穂, 認知心大会論文, 2012, 0, 119, 119, 2012年
  実験参加者自身により選択された項目の記憶保持は，実験者により割り当てられた項目に比べて優れる（自己選択効果）。本研究では，符号化時の自己選択により選択肢項目間の記憶の弁別が促されるか否かを検討した。実験参加者は，自身で選択（自己選択群）した単語，または実験者が選択（強制選択群）した単語を偶発学習した。10分後，全ての実験参加者はテスト項目として提示された各単語について記憶源の弁別をするように求められた。すなわち，実験参加者は各単語について選択した単語か，非選択の単語か，新しい単語かを判断した。その結果，強制選択群よりも自己選択群において弁別成績は高く，自己選択により選択肢項目の記憶が弁別されやすくなる可能性が支持された。, 日本認知心理学会
• 選択肢の再生における比較基準の影響(日本基礎心理学会第30回大会,大会発表要旨)
  伊藤 真利子; 綾部 早穂, 基礎心研, 30, 2, 226, 226, 2012年
  日本基礎心理学会, 日本語
• 単語の選択過程における注意の配分と単語再生成績の関係
  伊藤 真利子; 綾部 早穂, 筑波大学心理学研究 = Tsukuba psychological research, 44, 1, 6, 2012年
  筑波大学心理学系, 日本語
• 非選択項目の手がかり提示が自己選択効果に及ぼす影響
  伊藤 真利子; 関 那積; 井上 和哉; 菊地 正, 認知心大会論文, 2010, 0, 75, 75, 2010年
  学習時に実験参加者自身が複数の項目から一つを自由に選択できる場合には選択項目を割り当てられる場合よりも、後に項目の記憶成績が向上することが知られている（自己選択効果）。再生成績における自己選択効果の生起には、選択肢間の連合が重要である可能性が指摘されている(Hirano & Ukita, 2003; Watanabe & Soraci, 2004)。本研究では、既存の意味連合の利用が困難な選択肢を用いて生じる自己選択効果においても、選択肢間連合が再生成績の向上をもたらすかどうかを検討した。偶発学習段階の各試行において、実験参加者は選択肢(異なるカテゴリに属する2単語)について自己選択または強制選択を行うよう求められた。その後、選択肢間連合が再生成績に与える影響を調べるために、選択項目の検索手がかりとして非選択項目の提示の有無が操作され、選択項目の再生成績が比較された。, 日本認知心理学会, 日本語
• 選択肢間の意味連合が自己選択効果に及ぼす影響
  伊藤 真利子; 井上 和哉; 菊地 正, 認知心大会論文, 2009, 0, 89, 89, 2009年
  学習時に実験参加者自身が複数の項目から一つを自由に選択できる場合には項目を割り当てられる場合よりも、後のテスト時に選択項目の記憶成績が向上することが知られている（自己選択効果）。この説明として、自己選択条件では選択肢間連合が再生成績に貢献する可能性が指摘されている。本研究では、自己選択条件で既存の選択肢間連合の利用可能性が向上するだけなのか、新たな連合形成も促進されるのかを検討した。実験では、同じもしくは異なるカテゴリーに属する単語を選択肢として用いることで、既存の選択肢間意味連合の強度を操作した。偶発学習段階の各試行では、選択肢について自己選択または強制選択を行い、その後、単語の再生課題を行った。その結果、選択肢のカテゴリーの異同にかかわらず同程度の自己選択効果が認められた。この結果から、既存の選択肢間意味連合の強さは自己選択効果の生起にとって重要ではないことが示唆された。, 日本認知心理学会, 日本語
• 記憶の自己選択効果における比較の重要性
  伊藤 真利子; 菊地 正, 日心大会論文集, 72, 0, 3PM124, 3PM124, 2008年
  公益社団法人 日本心理学会, 日本語
• アウトプットモニタリングの概念的多義性に対する検討
  伊藤 真利子; 菊地 正, 筑波大学心理学研究, 34, 1, 7, 2007年08月17日
  筑波大学心理学系, 日本語
• アウトプットモニタリングエラーを検討するための一本指タイピング課題の提案
  伊藤 真利子; 菊地 正, 日心大会論文集, 71, 0, 3AM104, 3AM104, 2007年
  公益社団法人 日本心理学会, 日本語
• 急速反復書字におけるスリップの生起条件 : 部分文字により全体文字を書くことの影響(2004年度卒業論文)
  伊藤 真利子, 東京女子大学心理学紀要, 1, 8, 12, 2005年03月
  東京女子大学, 日本語

• 大学院共通授業科目（教育プログラム）：社会と健康, 2024年, 修士課程, 大学院共通科目

• PTSDの持続エクスポージャー療法の客観的治療効果指標に関する研究
  科学研究費助成事業
  2014年04月01日 - 2016年03月31日
  林 明明; 伊藤 真利子; 金 吉晴
  本研究では、心的外傷後ストレス障害（PTSD）に対して有効な治療法とされる持続エクスポージャー療法（PE）の客観的治療効果測定に役立つ指標について検討した。まず、PTSDの特徴を確認するため、質問紙法による心理指標、パソコン課題や検査バッテリーによる認知指標（全般的知能、全般的認知機能、ワーキングメモリ、実行機能、および記憶・注意の偏り）、自律神経指標をPTSD群と健常者群とで比較した。さらに、群間に差異が認められた指標に関してはPTSD症状との関連も検討した。その結果、全般的知能と注意機能の低下、ネガティブな情報への記憶の偏りは、PEの客観的測定指標の候補として有用である可能性が示された。
  日本学術振興会, 挑戦的萌芽研究, 国立研究開発法人国立精神・神経医療研究センター, 26590172