研究等業績 - 原著論文 - 三島 和夫
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Melatonin Treatment and Adequate Sleep Hygiene Interventions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial.
Masaharu Hayashi, Kazuo Mishima, Michio Fukumizu, Hiroyuki Takahashi, Yuko Ishikawa, Izumi Hamada, Hideyuki Sugioka, Osamu Yotsuya, Yushiro Yamashita
Journal of autism and developmental disorders 52 ( 6 ) 2784 - 2793 2021年06月 [査読有り]
研究論文（学術雑誌） 国内共著
Robust clinical evidence has not been available for melatonin, a drug commonly administered for treating sleep problems of children with autism spectrum disorder (ASD). In a phase 3 randomized, placebo-controlled clinical trial, we administered 1-mg melatonin (n = 65), 4-mg melatonin (n = 65), or placebo (n = 66) to196 children with ASD once daily before bedtime under adequate sleep hygiene interventions. The primary outcome was sleep onset latency (SOL) assessed with the electronic sleep diary. SOL shortened significantly in the 1- and 4-mg melatonin groups compared to the placebo group (- 22.0, - 28.0, and - 5.0 min, respectively; p < 0.0001 each). This therapeutic regimen of melatonin is a reasonable clinical approach to cope with ASD-emergent difficulties in children with ASD.
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Parthenogenetic mosaicism: generation via second polar body retention and unmasking of a likely causative PER2 variant for hypersomnia.
Yohei Masunaga, Masayo Kagami, Fumiko Kato, Takeshi Usui, Takako Yonemoto, Kazuo Mishima, Maki Fukami, Kazushi Aoto, Hirotomo Saitsu, Tsutomu Ogata
Clinical epigenetics 13 ( 1 ) 73 - 73 2021年04月 [査読有り]
研究論文（学術雑誌） 国内共著
BACKGROUND: Parthenogenetic mosaicism is an extremely rare condition identified only in five subjects to date. The previous studies indicate that this condition is mediated by parthenogenetic activation and is free from a specific phenotype ascribed to unmaking of a maternally inherited recessive variant in the parthenogenetic cell lineage. RESULTS: We examined a 28-year-old Japanese 46,XX female with Silver-Russell syndrome and idiopathic hypersomnia. The results revealed (1) predominance of maternally derived alleles for all the differentially methylated regions examined; (2) no disease-related copy-number variant; (3) two types of regions for all chromosomes, i.e., four BAF (B-allele frequency) band regions with single major microsatellite peaks of maternal origin and single minor microsatellite peaks of non-maternal (paternal) origin, and six BAF band regions with single major microsatellite peaks of maternal origin and two minor microsatellite peaks of maternal and non-maternal (paternal) origin; (4) an unmasked extremely rare PER2 variant (c.1403G>A:p.(Arg468Gln)) with high predicted pathogenicity; (5) mildly affected local structure with altered hydrogen bonds of the p.Arg468Gln-PER2 protein; and (6) nucleus-dominant subcellular distribution of the p.Arg468Gln-PER2 protein. CONCLUSIONS: The above findings imply that the second polar body retention occurred around fertilization, resulting in the generation of the parthenogenetic cell lineage by endoreplication of a female pronucleus and the normal cell lineage by fusion of male and female pronuclei, and that the homozygous PER2 variant in the parthenogenetic cells is the likely causative factor for idiopathic hypersomnia.
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Yamamoto M.
Neuropsychopharmacology Reports ( Neuropsychopharmacology Reports ) 41 ( 1 ) 14 - 25 2021年03月 [査読有り]
研究論文（学術雑誌） 国内共著
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Ken Inada, Minori Enomoto, Kentaro Yamato, Kazuo Mishima
Drugs - Real World Outcomes ( Springer Science and Business Media LLC ) 8 ( 3 ) 277 - 288 2021年03月 [査読有り]
研究論文（学術雑誌） 国内共著
BACKGROUND: Prolonged treatment of insomnia using benzodiazepine (BZD) receptor agonists, including BZD and non-BZD hypnotic drugs, can cause drug dependence, tolerance, abuse and other adverse events. These side effects are more common and/or severe in older adults taking different hypnotic drugs concomitantly. Therefore, a single prescription is limited to 30 daily doses for most BZD receptor agonists and restrictions apply to the prescription of more than three types of hypnotic drugs in Japan. Little is known, however, about the real-world prescribing pattern of hypnotic drugs in Japan. OBJECTIVE: We analysed prescribing patterns for hypnotic drugs in Japan to evaluate whether real-world use differs from guideline recommendations. METHODS: In this nationwide, retrospective, longitudinal, observational study, we analysed the types of hypnotic drugs prescribed, duration of medication and treatment setting in a subset of hospitals in Japan using a hospital-based administrative claims database (Medical Data Vision). Patients initiating treatment with hypnotic drugs between January 2012 and December 2016 were included in the analyses to assess the duration of medication and occurrence of co-prescription of a second and third hypnotic drug, within a year from prescription of the first hypnotic drugs. RESULTS: In 261,167 patients analysed, the first hypnotic drugs prescribed were BZDs (59.7%), non-BZDs (36.8%), a melatonin receptor agonist [MRA] (3.1%) and an orexin receptor antagonist [ORA] (0.4%). Benzodiazepine and non-BZD hypnotic drugs were mostly prescribed in inpatient settings (57.7% and 63.0%, respectively) and the MRA and ORA mostly in outpatient settings (62.6% and 65.4%, respectively). The departments that prescribed the most patients their first hypnotic drugs were internal medicine (23.6%), general surgery (11.8%), orthopaedic surgery (11.4%) and urology (5.3%). Of the total prescriptions of MRA and ORA as the first hypnotic drugs, 22.0% and 31.8% were in internal medicine, 4.4% each in general surgery, 6.0% and 4.5% in orthopaedic surgery, 9.7% and 4.4% in neurology, and 10.1% and 12.2% in psychiatry departments, respectively. Mean duration of medication was 1.13 months for non-BZDs, 1.15 months for BZDs, 1.29 months for the ORA and 1.83 months for the MRA. Overall, 5.3% (95% confidence interval 5.2-5.4) of patients were prescribed a second hypnotic drug; of these, 8.4% (95% confidence interval 8.0-8.9) were prescribed at least three hypnotic drugs within a year. Patients who were prescribed three or more hypnotic drugs received higher doses of the first drug than patients who received fewer hypnotic drugs. CONCLUSIONS: Benzodiazepine receptor agonists were the most common hypnotic drugs prescribed as the first drug to patients in Japan. Further education and awareness may be needed on the risk of complications and adverse events associated with these therapies. The duration of BZD receptor agonist use was shorter than for the MRA and ORA, in accordance with prescribing guidelines. Long-term use and co-prescribing of hypnotic drugs were also uncommon.
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Recurrence Rates in Stable Bipolar Disorder Patients after Drug Discontinuation versus Drug Maintenance: A Systematic Review and Meta-analysis - Corrigendum.
Taro Kishi, Yuki Matsuda, Kenji Sakuma, Makoto Okuya, Kazuo Mishima, Nakao Iwata
Psychological medicine 51 ( 15 ) 1 - 1 2021年03月 [査読有り]
研究論文（学術雑誌） 国内共著
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Decreased activity in the reward network of chronic insomnia patients
Motomura Y.
Scientific Reports ( Scientific Reports ) 11 ( 1 ) 2021年02月 [査読有り]
研究論文（学術雑誌） 国内共著
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Inada K.
Journal of Affective Disorders ( Journal of Affective Disorders ) 281 539 - 546 2021年02月 [査読有り]
研究論文（学術雑誌） 国内共著
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Kato M.
Molecular Psychiatry ( Molecular Psychiatry ) 26 ( 1 ) 118 - 133 2021年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Yamato K.
BMC Psychiatry ( BMC Psychiatry ) 21 ( 1 ) 2021年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Takeshima M.
Psychiatry and Clinical Neurosciences ( Psychiatry and Clinical Neurosciences ) 2021年 [査読有り]
研究論文（学術雑誌） 国内共著
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Kishi T.
Bipolar Disorders ( Bipolar Disorders ) 2021年 [査読有り]
研究論文（学術雑誌） 国内共著
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Tracking intermediate performance of vigilant attention using multiple eye metrics
Abe T.
Sleep ( Sleep ) 43 ( 3 ) 2021年 [査読有り]
研究論文（学術雑誌） 国内共著
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Factors Associated with Insomnia Among Truck Drivers in Japan.
Takashi Miyachi, Kyoko Nomura, Sachiko Minamizono, Kazuki Sakai, Toyoto Iwata, Yuta Sugano, Shun Sawaguchi, Kouhei Takahashi, Kazuo Mishima
Nature and science of sleep 13 613 - 623 2021年 [査読有り]
研究論文（学術雑誌） 国内共著
Purpose: Truck drivers with insomnia are at a high risk of traffic accidents. We aimed to investigate the prevalence of insomnia and identify its associated factors among truck drivers in Japan. Methods: Participants were 2927 male truck drivers younger than 65 years old. Self-administered questionnaires were used to assess insomnia symptoms, State-Trait Anxiety Inventory, drinking, smoking habits, body mass index, caffeine intake, as well as daily driving hours, consecutive days away from home, and driving distance. Insomnia symptoms included difficulty initiating sleep, maintaining sleep and early morning awakening. Insomnia was defined when any of these symptoms were observed with daily tiredness. Results: The prevalence of insomnia among the subjects was 13.3% (n=356), of which 13.5% had difficulty initiating sleep, 78% had difficulty maintaining sleep, and 26.4% had early morning awakening. After adjusting for covariates, drinking habits, daily driving hours, and STAI score were significantly and linearly associated with insomnia; the adjusted odds ratio (OR) of drinking habits for insomnia was 1.74 [95% confidence interval (CI), 1.23-2.47] for heavy drinkers compared to non-drinkers (trend p<0.001); the adjusted OR of daily driving hours was 1.87 (95% CI, 1.00-3.49) for 12 hours or longer in a day compared to <8 hours in a day (trend p<0.001); the adjusted OR of STAI quartiles was 5.30 (95% CI, 3.66-7.67) for the highest quartile compared to the lowest quartile (trend p<0.001). Conclusion: The present study demonstrated that insomnia is prevalent among truck drivers in Japan, and its risk factors include drinking habits, daily driving hours, and anxiety.
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Severity of Depressive Symptoms is Associated with Venous Thromboembolism in Hospitalized Patients with a Major Depressive Episode.
Kazuhisa Yoshizawa, Masahiro Takeshima, Sayaka Ishino, Masaya Ogasawara, Dai Fujiwara, Yu Itoh, Aya Imanishi, Hidenobu Ohta, Kazuo Mishima
Neuropsychiatric disease and treatment ( DOVE MEDICAL PRESS LTD ) 17 2955 - 2963 2021年 [査読有り]
研究論文（学術雑誌） 国内共著
Purpose: A major depressive episode is a risk factor for venous thromboembolism (VTE) in psychiatric inpatients. However, it is unclear whether the severity of depressive symptoms or duration of the current depressive episode is associated with VTE. Further, the VTE prevalence among hospitalized patients with a major depressive episode receiving electroconvulsive therapy is unknown. This retrospective study examined factors associated with VTE among hospitalized patients with a major depressive episode and estimated the prevalence of VTE in such patients who underwent electroconvulsive therapy. Patients and Methods: Patients with a major depressive episode hospitalized in the Department of Neuropsychiatry at Akita University Hospital between January 2018 and December 2020 were included. Data from the first week of hospitalization were extracted from medical records. VTE was diagnosed based on the findings of computed tomography. To evaluate whether the severity of depressive symptoms or duration of the current depressive episode was associated with VTE, logistic regression analysis was conducted after adjusting for covariates with known VTE risk factors (antidepressants, antipsychotics, and physical comorbidities). Results: We analyzed 133 patients; of these, 14 were diagnosed with asymptomatic VTE. The severity of depressive symptoms (odds ratio: 1.220, 95% confidence interval: 1.081-1.377, p = 0.001) was significantly associated with VTE. The prevalence of VTE among those receiving electroconvulsive therapy was 35% (7/20). Conclusion: The prevalence of VTE was 35% among patients receiving in-hospital electroconvulsive therapy for a major depressive episode. VTE should be considered for hospitalized patients with severe depressive symptoms and patients receiving in-hospital electroconvulsive therapy for a major depressive episode.
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The Usefulness of the Combination of D-Dimer and Soluble Fibrin Monomer Complex for Diagnosis of Venous Thromboembolism in Psychiatric Practice: A Prospective Study.
Masahiro Takeshima, Hiroyasu Ishikawa, Masaya Ogasawara, Munehiro Komatsu, Dai Fujiwara, Yu Itoh, Yuki Wada, Yuki Omori, Hidenobu Ohta, Kazuo Mishima
Vascular health and risk management ( DOVE MEDICAL PRESS LTD ) 17 239 - 246 2021年 [査読有り]
研究論文（学術雑誌） 国内共著
Purpose: D-dimer has the advantage of excluding venous thromboembolism (VTE) due to its high sensitivity but is disadvantageous for diagnosing VTE due to its low specificity. A method to increase the usefulness of D-dimer in the diagnosis of VTE is warranted. This study aimed to investigate the usefulness of the combination of D-dimer and soluble fibrin monomer complex (SFMC), which has been suggested as a new candidate marker for VTE, in VTE diagnosis. Patients and Methods: This prospective study in 109 subjects was performed at a psychiatric department between August 1, 2017 and December 31, 2019. Subjects' levels of D-dimer and SFMC were measured simultaneously. Plasma levels of D-dimer and SFMC were measured using NANOPIA® D-dimer and NANOPIA® SF. Subjects with positive D-dimer (≥1.0 µg/mL) results underwent contrast computed tomography for confirmation of VTE within 12 hours of D-dimer measurement. A receiver operating characteristic curve analysis was performed to examine the usefulness of SFMC for the diagnosis of VTE. Results: Only 109 of the 783 subjects without symptoms suggestive of VTE participated in the study. Out of 41 subjects with positive D-dimer results, 17 subjects were diagnosed with VTE. A receiver operating characteristic curve analysis was performed to determine cutoff values. The area under the curves was 0.848 for SFMC (p<0.001, 95% CI 0.722 to 0.974), and the optimal cutoff value was 10.0 µg/mL (sensitivity 58.8%, specificity 100%, positive predictive value 100%, negative predictive value 77.4%). Conclusion: SFMC was useful for diagnosing VTE in the psychiatric patients with positive D-dimer results.
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Ishizuya A.
Scientific Reports ( Scientific Reports ) 11 ( 1 ) 2020年12月 [査読有り]
研究論文（学術雑誌） 国内共著
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Imanishi A.
Orphanet Journal of Rare Diseases ( Orphanet Journal of Rare Diseases ) 15 ( 1 ) 2020年09月 [査読有り]
研究論文（学術雑誌） 国内共著
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Yuge K.
BMC Psychiatry ( BMC Psychiatry ) 20 ( 1 ) 2020年09月 [査読有り]
研究論文（学術雑誌） 国内共著
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Kishi T.
Journal of clinical psychopharmacology ( Journal of clinical psychopharmacology ) 40 ( 5 ) 468 - 474 2020年09月 [査読有り]
研究論文（学術雑誌） 国内共著
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Yuya Takahashi, Sho Shindo, Takashi Kanbayashi, Masahiro Takeshima, Aya Imanishi, Kazuo Mishima
Neuropsychopharmacology reports ( Wiley ) 40 ( 1 ) 10 - 15 2020年03月 [査読有り]
研究論文（学術雑誌） 国内共著
We examined whether symptoms of dementia are improved by olfactory nerve stimulation in Alzheimer type dementia patients. First, a stick-type olfactory identification ability test was performed in patients with Alzheimer type dementia, to select patients without olfactory dysfunctions. Then, these patients were randomly assigned into the intervention (n = 19) and the control groups (n = 17). To evaluate the effects of olfactory nerve stimulation, we exposed the intervention group to a disinfecting ethanol with added aroma extracts from ceder and the control group to the ethanol without the added aroma extracts. Each group underwent the intervention for 8 weeks, cognitive and behavioral functions were evaluated before and after treatments using the Neuropsychiatric Inventory (NPI), the Japanese version of Zarit Caregiver Burden interview (J-ZBI), and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). A significant improvement was observed in the NPI score and J-ZBI in the intervention group compared to the control group at 4 and 8 weeks. On the other hand, there was no significant difference in the score of ADAS-cog. Exposure to cedar fragrance improved behavioral and psychological symptoms of dementia (BPSD) in Alzheimer type dementia and may reduce the burden of nursing care. In addition to its effectiveness, the procedure is simple and minimally invasive and would be a valuable non-pharmaceutical treatment.