研究者詳細 - 内田　裕之

論文 - 内田　裕之

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NO-Rich Diet for Lifestyle-Related Diseases.

Kobayashi J, Ohtake K, Uchida H

Nutrients 7 （ 6 ） 4911 - 37 2015年06月

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A questionnaire survey of Japanese non-psychiatrists' attitudes on management of depression in a general hospital

Ikai Saeko, Suzuki Takefumi, Uchida Hiroyuki, Saito Hisaaki, Mimura Masaru, Takeuchi Hiroyoshi

Asian Journal of Psychiatry 15 73 - 74 2015年06月

ISSN 1876-2018

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研究と報告　日本版短縮感覚プロフィールの標準化　標準値および信頼性・妥当性の検討

谷伊織, 伊藤大幸, 平島太郎, 岩永竜一郎, 萩原拓, 行廣隆次, 内山登紀夫, 小笠原恵, 黒田美保, 稲田尚子, 原幸一, 井上雅彦, 村上隆, 染木史緒, 中村和彦, 杉山登志郎, 内田裕之, 市川宏伸, 辻井正次

精神医学（(株)医学書院） 57 （ 6 ） 419 - 429 2015年06月

ISSN 0488-1281

本研究では,感覚刺激への反応異常のアセスメントツールとして国際的に広く用いられている短縮感覚プロフィールの日本版の標準化に関する研究の一環として,1,441名の標準化サンプルと317名の臨床サンプルのデータに基づき,日本版短縮感覚プロフィール(SSP-J)の信頼性および妥当性,標準値の検討を行った。分析の結果,SSP-Jを構成する質問項目は全般的に高い修正済み項目全体間相関を示し,α係数を検討した結果,十分な内的整合性を有していた。また,臨床サンプルにおけるSSP-Jの各セクションの得点と知能,ASD症状,適応行動との相関より,基準関連妥当性が示された。(著者抄録)

Fear conditioning induced by interpersonal conflicts in healthy individuals

Tada M., Uchida H., Maeda T., Konishi M., Umeda S., Terasawa Y., Nakajima S., Mimura M., Miyazaki T., Takahashi T.

PLoS ONE （PLoS ONE） 10 （ 5 ） e0125729 2015年05月

© 2015 Tada et al. Psychophysiological markers have been focused to investigate the psychopathology of psychiatric disorders and personality subtypes. In order to understand neurobiological mechanisms underlying these conditions, fear-conditioning model has been widely used. However, simple aversive stimuli are too simplistic to understand mechanisms because most patients with psychiatric disorders are affected by social stressors. The objective of this study was to test the feasibility of a newly-designed conditioning experiment using a stimulus to cause interpersonal conflicts and examine associations between personality traits and response to that stimulus. Twenty-nine healthy individuals underwent the fear conditioning and extinction experiments in response to three types of stimuli: a simple aversive sound, disgusting pictures, and pictures of an actors' face with unpleasant verbal messages that were designed to cause interpersonal conflicts. Conditioned response was quantified by the skin conductance response (SCR). Correlations between the SCR changes, and personality traits measured by the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) and Revised NEO Personality Inventory were explored. The interpersonal conflict stimulus resulted in successful conditioning, which was subsequently extinguished, in a similar manner as the other two stimuli. Moreover, a greater degree of conditioned response to the interpersonal conflict stimulus correlated with a higher ZANBPD total score. Fear conditioning and extinction can be successfully achieved, using interpersonal conflicts as a stimulus. Given that conditioned fear caused by the interpersonal conflicts is likely associated with borderline personality traits, this paradigm could contribute to further understanding of underlying mechanisms of interpersonal fear implicated in borderline personality disorder.

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Dopamine D<inf>2/3</inf> receptor availability in the striatum of antipsychotic-free older patients with schizophrenia-A [11C]-raclopride PET study

Nakajima Shinichiro, Caravaggio Fernando, Mamo David C., Mulsant Benoit H., Chung Jun Ku, Plitman Eric, Iwata Yusuke, Gerretsen Philip, Uchida Hiroyuki, Suzuki Takefumi, Mar Wanna, Wilson Alan A., Houle Sylvain, Graff-Guerrero Ariel

Schizophrenia Research 164 （ 1-3 ） 263 - 267 2015年05月

ISSN 0920-9964

Background: No study has examined dopamine D<inf>2/3</inf> receptor (D<inf>2/3</inf>R) availability in antipsychotic-free older patients with schizophrenia. Methods: We included patients with schizophrenia 50years or older who were antipsychotic-free for at least 3months. We compared non-displaceable binding potential (BP<inf>ND</inf>) of [11C]-raclopride in the caudate, putamen, ventral striatum, and globus pallidus between patients and age- and sex-matched healthy controls. Results: Ten patients participated (antipsychotic-naive=4). No differences in BP<inf>ND</inf> were found between patients and controls in any ROIs (F(1, 72)=42, p=52). Conclusion: The preliminary results suggest no differences in D<inf>2/3</inf>R availability between antipsychotic-free older patients with schizophrenia and controls.

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Antipsychotic Polypharmacy and Corrected QT Interval

Takeuchi Hiroyoshi, Suzuki Takefumi, Remington Gary, Uchida Hiroyuki

Canadian Journal of Psychiatry 60 （ 5 ） 215 - 222 2015年05月

ISSN 0706-7437

RESULTS: A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.CONCLUSIONS: Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.OBJECTIVE: It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.METHOD: A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.

Cardiac Sudden Death in Psychiatric Patients

Uchida Hiroyuki, Suzuki Takefumi

Canadian Journal of Psychiatry 60 （ 5 ） 203 - 205 2015年05月

ISSN 0706-7437

Challenging the need for sustained blockade of dopamine D<inf>2</inf> receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia

Tsuboi Takashi, Suzuki Takefumi, Bies Robert R., Remington Gary, Pollock Bruce G., Mimura Masaru, Uchida Hiroyuki

Schizophrenia Research 164 （ 1-3 ） 149 - 154 2015年05月

ISSN 0920-9964

Objective: Blockade of dopamine D<inf>2</inf> receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment. Method: In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D<inf>2</inf> blockade (i.e. an estimated trough D<inf>2</inf> blockade of >65%) or non-continuous blockade group (i.e. an estimated peak level of >65% with an estimated trough level of <65%). Oral doses corresponding to the assigned blockade levels were estimated from random plasma drug concentrations, using the models we developed; antipsychotic doses were then adjusted accordingly. Psychopathology and side effects were assessed at baseline and one year with the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). Results: Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups. Conclusion: These results offer support that the threshold for D<inf>2</inf> receptor blockade in the maintenance treatment can be lower than 65%. However, these preliminary findings have to be confirmed through double-blind, larger scale trials with longer follow-up periods.

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Antipsychotic polypharmacy and corrected QT interval: A systematic review

Takeuchi H., Suzuki T., Remington G., Uchida H.

Canadian Journal of Psychiatry （Canadian Journal of Psychiatry） 60 （ 5 ） 215 - 222 2015年05月

ISSN 07067437

Objective: It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue. Method: A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups. Results: A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy. Conclusions: Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.

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Dopamine D<inf>2/3</inf> receptor availability in the striatum of antipsychotic-free older patients with schizophrenia-A [11C]-raclopride PET study

Nakajima S., Caravaggio F., Mamo D., Mulsant B., Chung J., Plitman E., Iwata Y., Gerretsen P., Uchida H., Suzuki T., Mar W., Wilson A., Houle S., Graff-Guerrero A.

Schizophrenia Research （Schizophrenia Research） 164 （ 1-3 ） 263 - 267 2015年05月

ISSN 09209964

© 2015 Elsevier B.V. Background: No study has examined dopamine D2/3 receptor (D2/3R) availability in antipsychotic-free older patients with schizophrenia. Methods: We included patients with schizophrenia 50years or older who were antipsychotic-free for at least 3months. We compared non-displaceable binding potential (BPND) of [11C]-raclopride in the caudate, putamen, ventral striatum, and globus pallidus between patients and age- and sex-matched healthy controls. Results: Ten patients participated (antipsychotic-naive=4). No differences in BPND were found between patients and controls in any ROIs (F(1, 72)=42, p=52). Conclusion: The preliminary results suggest no differences in D2/3R availability between antipsychotic-free older patients with schizophrenia and controls.

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Challenging the need for sustained blockade of dopamine D<inf>2</inf> receptor estimated from antipsychotic plasma levels in the maintenance treatment of schizophrenia: A single-blind, randomized, controlled study

Tsuboi T., Suzuki T., Bies R., Remington G., Pollock B., Mimura M., Uchida H.

Schizophrenia Research （Schizophrenia Research） 164 （ 1-3 ） 149 - 154 2015年05月

ISSN 09209964

© 2015 Elsevier B.V. Objective: Blockade of dopamine D2 receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment. Method: In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D2 blockade (i.e. an estimated trough D2 blockade of >65%) or non-continuous blockade group (i.e. an estimated peak level of >65% with an estimated trough level of <65%). Oral doses corresponding to the assigned blockade levels were estimated from random plasma drug concentrations, using the models we developed; antipsychotic doses were then adjusted accordingly. Psychopathology and side effects were assessed at baseline and one year with the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Scale (SAS), and Abnormal Involuntary Movement Scale (AIMS). Results: Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups. Conclusion: These results offer support that the threshold for D2 receptor blockade in the maintenance treatment can be lower than 65%. However, these preliminary findings have to be confirmed through double-blind, larger scale trials with longer follow-up periods.

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Whether to increase or maintain dosage of mirtazapine in early nonimprovers with depression

Ueno F., Nakajima S., Suzuki T., Abe T., Sato Y., Mimura M., Uchida H.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry） 76 （ 4 ） 434 - 439 2015年04月

ISSN 0160-6689

© Copyright 2015 Physicians Postgraduate Press, Inc. Objective: To compare outcomes between increasing versus maintaining the dose of mirtazapine in patients with depression without initial improvement. Method: Data from a 6-week double-blind randomized placebo-controlled trial of mirtazapine in major depressive disorder (DSM-IV) conducted from November 2004 to December 2005 were used. Percentages of remitters (ie, a score of ≤ 7 in the 17-item Hamilton Depression Rating Scale [HDRS-17]) and HDRS-17 score changes from baseline to week 6 were compared in the following 2 pairs, using Fisher exact test or mixed-effects model for repeated measures: (1) subjects who failed to show a ≥ 20% decrease in the HDRS-17 total scores at week 1 but were assigned to continue 15 mg/d (stay<inf>15</inf> group) versus those who were assigned to increase the dose to 30 mg/d (increase<inf>30</inf> group) and (2) subjects who failed to show a ≥ 20% decrease in the HDRS-17 total scores with 30 mg/d at week 2 but were assigned to continue 30 mg/d (stay<inf>30</inf> group) versus those who were assigned to increase the dose to 45 mg/d (increase45 group). Results: The increase<inf>30</inf> group showed a numerically but not significantly higher remission rate and a significantly greater decrease in the HDRS-17 total score at week 6 than the stay<inf>15</inf> group (34.7% [8 of 23 patients] vs 14.3% [3 of 21 patients], P = .2; least squares mean, -15.8 vs -10.9, P = .003). No significant differences were found between the increase<inf>45</inf> and stay<inf>30</inf> groups. Conclusions: Dose increase of mirtazapine from 15 mg/d to 30 mg/d may be effective for patients with depression without initial improvement. However, effectiveness may not be the case beyond 30 mg/d.

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Improvement in treatment results of glioblastoma over the last three decades and beneficial factors.

Kawano H, Hirano H, Yonezawa H, Yunoue S, Yatsushiro K, Ogita M, Hiraki Y, Uchida H, Habu M, Fujio S, Oyoshi T, Bakhtiar Y, Sugata S, Yamahata H, Hanaya R, Tokimura H, Arita K

British journal of neurosurgery 29 （ 2 ） 206 - 12 2015年04月

ISSN 0268-8697

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Steroid psychosis caused by perioperative steroid replacement for pituitary adenoma

Mizutani Katsuhiro, Toda Masahiro, Kikuchi Ryogo, Uchida Hiroyuki, Yoshida Kazunari

Keio Journal of Medicine 64 （ 1 ） 11 - 15 2015年03月

ISSN 0022-9717

Steroid psychosis is a frequent complication of steroid treatment. Although perioperative steroid replacement therapy is generally administered in patients undergoing pituitary surgery, there are no previous reports concerning the development of steroid psychosis after perioperative steroid replacement therapy following pituitary surgery. We herein report a case of steroid psychosis induced by perioperative steroid replacement therapy for pituitary surgery. A 35-year-old man presented with a visual disturbance that had persisted for 1 year. A magnetic resonance imaging scan showed a large pituitary tumor, and a laboratory study revealed slight dysfunction of the hypothalamo-pituitary-adrenal axis. The patient was diagnosed with a non-functioning pituitary tumor and underwent tumor resection via the endoscopic endonasal approach. The initial dose of perioperative steroid replacement therapy was 200 mg of hydrocortisone administered immediately before the operation. The replacement dose was gradually tapered and discontinued over a 7-day period. On postoperative day 4, the patient exhibited an elated mood, grandiose delusions, anxiety, and agitation. We diagnosed these psychiatric symptoms as steroid psychosis induced by steroid replacement and we prescribed risperidone as a treatment. The symptoms gradually improved and did not recur. This case highlights the risk of steroid psychosis following treatment with perioperative steroid replacement therapy for pituitary adenoma and raises questions regarding the appropriateness of perioperative steroid replacement for pituitary adenoma.

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Steroid psychosis caused by perioperative steroid replacement for pituitary adenoma: A case report

Mizutani K., Toda M., Kikuchi R., Uchida H., Yoshida K.

Keio Journal of Medicine （Keio Journal of Medicine） 64 （ 1 ） 11 - 15 2015年03月

ISSN 00229717

© 2015 by The Keio Journal of Medicine. Steroid psychosis is a frequent complication of steroid treatment. Although perioperative steroid replacement therapy is generally administered in patients undergoing pituitary surgery, there are no previous reports concerning the development of steroid psychosis after perioperative steroid replacement therapy following pituitary surgery. We herein report a case of steroid psychosis induced by perioperative steroid replacement therapy for pituitary surgery. A 35-year-old man presented with a visual disturbance that had persisted for 1 year. A magnetic resonance imaging scan showed a large pituitary tumor, and a laboratory study revealed slight dysfunction of the hypothalamo-pituitary-adrenal axis. The patient was diagnosed with a non-functioning pituitary tumor and underwent tumor resection via the endoscopic endonasal approach. The initial dose of perioperative steroid replacement therapy was 200 mg of hydrocortisone administered immediately before the operation. The replacement dose was gradually tapered and discontinued over a 7-day period. On postoperative day 4, the patient exhibited an elated mood, grandiose delusions, anxiety, and agitation. We diagnosed these psychiatric symptoms as steroid psychosis induced by steroid replacement and we prescribed risperidone as a treatment. The symptoms gradually improved and did not recur. This case highlights the risk of steroid psychosis following treatment with perioperative steroid replacement therapy for pituitary adenoma and raises questions regarding the appropriateness of perioperative steroid replacement for pituitary adenoma.

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Corrigendum to Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia

Takeuchi Hiroyoshi, Suzuki Takefumi, Bies Robert R., Remington Gary, Mamo David C., Pollock Bruce G., Uchida Hiroyuki

Schizophrenia Research 162 （ 1-3 ） 296 2015年03月

ISSN 0920-9964

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Dependence on benzodiazepines in patients with panic disorder

Fujii Kazuhito, Uchida Hiroyuki, Suzuki Takefumi, Mimura Masaru

Psychiatry and Clinical Neurosciences 69 （ 2 ） 93 - 99 2015年02月

ISSN 1323-1316

Aims The aim of this cross-sectional study was to examine the prevalence of psychological dependence on benzodiazepines in outpatients with panic disorder and elucidate demographic and clinical characteristics associated with this condition. Methods Subjects were eligible if they were outpatients in four clinics in Tokyo, Japan, aged 18 years or older and met the diagnostic criteria for panic disorder according to the ICD-10. The subjects received the following assessments: the Severity of Dependence Scale, Japanese Version (SDS), the Self-Report Version of Panic Disorder Severity Scale, Japanese Version (PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report, Japanese Version. The following information was also collected: age, sex, ethnicity, duration of illness, physical and psychiatric comorbidities, and details of prescribed psychotropic medications. Results The data from 51 outpatients showed that 31 patients (60.8%) showed psychological dependence (i.e. a total score of ≥5 in the SDS). The proportion of patients with dependence was significantly lower in remitted patients (i.e. a total score of ≤4 in the PDSS) (44.1%, n-=-15/34) than those who were not (94.1%, n-=-16/17) (Pearson χ²-=-11.9, P-<-0.001). A multiple regression analysis showed that the PDSS scores showed a positive correlation with the SDS total scores (β-=-0.60, 95% confidence interval-=-0.30-0.90, P-=-0.0001). Conclusion These findings emphasize the need for enhanced awareness about benzodiazepine dependence in patients and psychiatrists, as well as especially close attention to patients with panic disorder who present severe symptomatology.

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Dependence on benzodiazepines in patients with panic disorder: A cross-sectional study

Fujii K., Uchida H., Suzuki T., Mimura M.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 69 （ 2 ） 93 - 99 2015年02月

ISSN 13231316

© 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology. Aims The aim of this cross-sectional study was to examine the prevalence of psychological dependence on benzodiazepines in outpatients with panic disorder and elucidate demographic and clinical characteristics associated with this condition. Methods Subjects were eligible if they were outpatients in four clinics in Tokyo, Japan, aged 18 years or older and met the diagnostic criteria for panic disorder according to the ICD-10. The subjects received the following assessments: the Severity of Dependence Scale, Japanese Version (SDS), the Self-Report Version of Panic Disorder Severity Scale, Japanese Version (PDSS-SR), and the Quick Inventory of Depressive Symptomatology-Self Report, Japanese Version. The following information was also collected: age, sex, ethnicity, duration of illness, physical and psychiatric comorbidities, and details of prescribed psychotropic medications. Results The data from 51 outpatients showed that 31 patients (60.8%) showed psychological dependence (i.e. a total score of ≥5 in the SDS). The proportion of patients with dependence was significantly lower in remitted patients (i.e. a total score of ≤4 in the PDSS) (44.1%, n-=-15/34) than those who were not (94.1%, n-=-16/17) (Pearson χ2-=-11.9, P-<-0.001). A multiple regression analysis showed that the PDSS scores showed a positive correlation with the SDS total scores (β-=-0.60, 95% confidence interval-=-0.30-0.90, P-=-0.0001). Conclusion These findings emphasize the need for enhanced awareness about benzodiazepine dependence in patients and psychiatrists, as well as especially close attention to patients with panic disorder who present severe symptomatology.

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Dietary nitrite supplementation improves insulin resistance in type 2 diabetic KKA(y) mice.

Ohtake K, Nakano G, Ehara N, Sonoda K, Ito J, Uchida H, Kobayashi J

Nitric oxide : biology and chemistry 44 31 - 8 2015年01月

ISSN 1089-8603

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A Proposal for Natural Resilience Theory in Psychopharmacotherapy

Yagi Gohei, Suzuki Takefumi, Uchida Hiroyuki

Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 117 （ 1 ） 10 - 17 2015年01月

ISSN 0033-2658

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内田 裕之

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