Details of a Researcher - Uchida, Hiroyuki

Papers - Uchida, Hiroyuki

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Dopamine D<inf>2</inf> receptor occupancy and cognition in schizophrenia: Analysis of the CATIE data

Sakurai H., Bies R., Stroup S., Keefe R., Rajji T., Suzuki T., Mamo D., Pollock B., Watanabe K., Mimura M., Uchida H.

Schizophrenia Bulletin (Schizophrenia Bulletin) 39 ( 3 ) 564 - 574 2013.05

ISSN 05867614

Introduction: Antipsychotic drugs exert antipsychotic effects by blocking dopamine D2 receptors in the treatment of schizophrenia. However, effects of D2 receptor blockade on neurocognitive function still remain to be elucidated. The objective of this analysis was to evaluate impacts of estimated dopamine D2 receptor occupancy with antipsychotic drugs on several domains of neurocognitive function in patients with schizophrenia in the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial. Methods: The dataset from the CATIE trial was used in the present analysis. Data were extracted from 410 subjects who were treated with risperidone, olanzapine, or ziprasidone, received assessments for neurocognitive functions (verbal memory, vigilance, processing speed, reasoning, and working memory) and psychopathology, and provided plasma samples for the measurement of plasma antipsychotic concentrations. D2 receptor occupancy levels on the day of neurocognitive assessment were estimated from plasma antipsychotic concentrations, using population pharmacokinetic analysis and our recently developed model. A multivariate general linear model was used to examine effects of clinical and demographic characteristics, including estimated D2 occupancy levels, on neurocognitive functions. Results: D2 occupancy levels showed significant associations with the vigilance and the summary scores. Neurocognitive functions, including vigilance, were especially impaired in subjects who showed D2 receptor occupancy level of >77%. Discussion: These findings suggest a nonlinear relationship between prescribed antipsychotic doses and overall neurocognitive function and vigilance. This study shows that D2 occupancy above approximately 80% not only increases the risk for extrapyramidal side effects as consistently reported in the literature but also increases the risk for cognitive impairment. © 2012 The Author.

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Factor structure of the Targeted Inventory on Problems in Schizophrenia

Tanaka Shoji, Nagase Takanori, Suzuki Takefumi, Nomura Kensuke, Takeuchi Hiroyoshi, Nakajima Shinichiro, Uchida Hiroyuki, Yagi Gohei, Watanabe Koichiro, Mimura Masaru

Clinical Psychopharmacology and Neuroscience (Clinical Psychopharmacology and Neuroscience) 11 ( 1 ) 18 - 23 2013.04

ISSN 1738-1088

The aim of this study was to explore the factor structure of a novel, 10-item rating scale, the Targeted Inventory on Problems in Schizophrenia (TIP-Sz). Determining the factor structure will be useful in the brief evaluation of medication and non-medication treatment of the disease. Methods: An exploratory factor analysis was performed on TIP-Sz scores obtained from 100 patients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for schizophrenia. Results: The factor analysis extracted four factors that were deemed clinically pertinent, which we labeled: disorganization, social cooperativeness, functional capacity, and emotional state. The items exhibited cross-loadings on the first three factors (i.e., some items loaded on more than one factor). In particular, the 'behavioral dyscontrol and disorganization,' 'insight and reality testing,' and 'overall prognostic impression' items had comparable cross-loadings on all of the first three factors. The emotional state factor was distinct from the other factors in that the items loading on it did not cross-load on other factors. Conclusion: The TIP-Sz scale comprises factors that are associated with the psychosocial functioning and emotional state of patients, which are important outcome parameters for successful treatment of the disease.

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Direct STM elucidation of the effects of atomic-level structure on Pt(111) electrodes for dissolved CO oxidation.

Inukai J, Tryk DA, Abe T, Wakisaka M, Uchida H, Watanabe M

Journal of the American Chemical Society 135 ( 4 ) 1476 - 90 2013.01

ISSN 0002-7863

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Antipsychotic polypharmacy in schizophrenia. How to counteract this common practice?

Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Mimura Masaru

Polypharmacy in Psychiatry Practice Volume II: Use of Polypharmacy in the "real world" (Polypharmacy in Psychiatry Practice Volume II: Use of Polypharmacy in the "real world") 81 - 107 2013.01

Antipsychotic polypharmacy (using multiple antipsychotics simultaneously) in schizophrenia appears to be a common practice in the real world. However, it has been a practice with substantial debate for its possible pros and cons. In this section, we systematically review clinical evidence on antipsychotic polypharmacy in schizophrenia. We first focus on the prevalence of antipsychotic polypharmacy in schizophrenia in the real-world clinical settings, to highlight the fact that it is becoming a frequent reality. Next, we discuss potential mechanisms that lead to such a controversial practice. Then, meta-analyses and systematic reviews that addressed the usefulness of antipsychotic polypharmacy in schizophrenia are qualitatively assessed.The results of this critical appraisal on the currently available evidence indicate that usefulness of antipsychotic polypharmacy in schizophrenia has been a focus of extensive research. However, there are practically too many possible combinations to be evaluated with each antipsychotic dosage also in mind. Evidence on antipsychotic polypharmacy currently remains equivocal at best even for polypharmacy involving clozapine; it is all the more questionable for other mode of antipsychotic combination therapy. Moreover, there has been no study that evaluated antipsychotic polypharmacy in reference with other various augmentation strategies that may potentially be effective.While a possibility cannot be denied for clinical usefulness of some mode of antipsychotic combination therapy in schizophrenia in general (e.g., combining prolactin-raising or metabolically problematic antipsychotics with more benign agents) or on an individual basis (i.e., for treatment-resistant schizophrenia), the currently available evidence supports the notion that prescribers should remain very conservative in resorting to antipsychotic polypharmacy. In other words, physicians should keep in mind the very basic of pharmacotherapy in every field of medicine; medications should be simple at least at early stages of treatment unless evidence unequivocally points to the contrary.An effort will be made to synthesize the currently available evidence to be translated into future directions on this critically relevant topic. Further, potential strategies to counteract antipsychotic polypharmacy in schizophrenia are discussed in detail. More work is clearly indicated for this important issue that will remain a matter of hot debate for the years to come.

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Interventions to reduce antipsychotic polypharmacy

Tani Hideaki, Uchida Hiroyuki, Suzuki Takefumi, Fujii Yasuo, Mimura Masaru

Schizophrenia Research 143 ( 1 ) 215 - 220 2013.01

ISSN 0920-9964

Background: It still remains unclear as to how to counteract antipsychotic polypharmacy that remains controversial but common. The objective of this study was to synthesize the clinical evidence to reduce antipsychotic polypharmacy (i.e. use of multiple antipsychotics) in schizophrenia. Methods: A literature search was performed to identify clinical trials that attempted to reduce antipsychotic polypharmacy in patients with schizophrenia by any form of systematic intervention using PubMed as well as MEDLINE, EMBASE, and PsycINFO (last search: June 2012). The search terms included "antipsychotics" and "polypharmacy". Cross-referencing was also performed. Results: The literature search identified 17 studies. Only 3 studies (1 randomized controlled trial and 2 open-label trials) were found that systematically switched antipsychotic polypharmacy to monotherapy. In two of them, more than two thirds of the subjects successfully completed the switch (40/58, 69.0%; 34/44, and 77.3%, respectively) while less than half the subjects tolerated it in the other study (6/14 and 42.9%) although the sample size was very small. On the other hand, 14 studies that examined impacts of interventions have physicians refrain from antipsychotic polypharmacy. While a modest intervention with educational approach alone was effective in three of the five articles, a more assertive intervention that directly cautioned physicians on the use of polypharmacy was effective in 10 of 12 articles. Conclusion: The literature search revealed the paucity of the data. Careful switching from polypharmacy to monotherapy seems feasible in a majority of patients with schizophrenia. Assertive interventions, rather than passive educational approaches alone, appear more effective in reducing antipsychotic polypharmacy.

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Interventions to reduce antipsychotic polypharmacy: A systematic review

Tani H., Uchida H., Suzuki T., Fujii Y., Mimura M.

Schizophrenia Research (Schizophrenia Research) 143 ( 1 ) 215 - 220 2013.01

ISSN 09209964

Background: It still remains unclear as to how to counteract antipsychotic polypharmacy that remains controversial but common. The objective of this study was to synthesize the clinical evidence to reduce antipsychotic polypharmacy (i.e. use of multiple antipsychotics) in schizophrenia. Methods: A literature search was performed to identify clinical trials that attempted to reduce antipsychotic polypharmacy in patients with schizophrenia by any form of systematic intervention using PubMed as well as MEDLINE, EMBASE, and PsycINFO (last search: June 2012). The search terms included "antipsychotics" and "polypharmacy". Cross-referencing was also performed. Results: The literature search identified 17 studies. Only 3 studies (1 randomized controlled trial and 2 open-label trials) were found that systematically switched antipsychotic polypharmacy to monotherapy. In two of them, more than two thirds of the subjects successfully completed the switch (40/58, 69.0%; 34/44, and 77.3%, respectively) while less than half the subjects tolerated it in the other study (6/14 and 42.9%) although the sample size was very small. On the other hand, 14 studies that examined impacts of interventions have physicians refrain from antipsychotic polypharmacy. While a modest intervention with educational approach alone was effective in three of the five articles, a more assertive intervention that directly cautioned physicians on the use of polypharmacy was effective in 10 of 12 articles. Conclusion: The literature search revealed the paucity of the data. Careful switching from polypharmacy to monotherapy seems feasible in a majority of patients with schizophrenia. Assertive interventions, rather than passive educational approaches alone, appear more effective in reducing antipsychotic polypharmacy. © 2012 Elsevier B.V.

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Effect of poly-L-arginine on intestinal absorption of hydrophilic macromolecules in rats.

Yamaki T, Uchida M, Kuwahara Y, Shimazaki Y, Ohtake K, Kimura M, Uchida H, Kobayashi J, Ogihara M, Morimoto Y, Natsume H

Biological & pharmaceutical bulletin 36 ( 3 ) 496 - 500 2013

ISSN 0918-6158

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Poly-L-arginine-Induced internalization of tight junction proteins increases the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules.

Yamaki T, Ohtake K, Ichikawa K, Uchida M, Uchida H, Oshima S, Juni K, Kobayashi J, Morimoto Y, Natsume H

Biological & pharmaceutical bulletin 36 ( 3 ) 432 - 41 2013

ISSN 0918-6158

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Effect of platinum loading on fuel cell cathode performance using hydrocarbon ionomers as binders.

Omata T, Uchida M, Uchida H, Watanabe M, Miyatake K

Physical chemistry chemical physics : PCCP 14 ( 48 ) 16713 - 8 2012.12

ISSN 1463-9076

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Deficit status in bipolar disorder

Nio Shintaro, Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Mimura Masaru

Journal of Affective Disorders 143 ( 1-3 ) 248 - 252 2012.12

ISSN 0165-0327

Objective: While the Kraepelinian dichotomy explicitly distinguishes between schizophrenia and bipolar disorder, it remains unclear as to whether a deficit form of bipolar disorder exists. Method: We conducted a study to investigate the prevalence rate of the deficit form of bipolar disorder; the criteria of which were basically adopted by the original proposal for schizophrenia that described the predominance of negative symptoms for over a year. Moreover, we presented a series of cases with deficit bipolar disorder to characterize its clinical pictures in detail. Results: Consecutive outpatients who visited one psychiatric hospital in Tokyo, Japan in March 2007 were evaluated cross-sectionally. Additionally, medical charts of inpatients who were hospitalized in the same hospital between April 2006 and March 2007 were also thoroughly reviewed. Of 494 patients, 7 patients (1.4%; 10.9% of 64 bipolar cases) fulfilled the criteria for bipolar disorder with deficit syndrome. Seven deficit cases had a mean±SD age of 61±5 year-old with the age at onset being 25±8 year-old. In addition to pervasive negative symptoms, they exhibited evidence of cognitive impairments close to the magnitude of what is usually noted in schizophrenia (i.e. a mean±SD total IQ score of 80±9 in the Wechsler Adult Intelligence Scale and 0.4±0.5 in the Wisconsin Card Sorting Test, categories achieved). Conclusion: Although preliminary, the evidence on deficit status in patients with bipolar disorder that we found in this study appears more consistent with recent evidence and challenges the Kraepelinian dichotomy that reserves deficit status solely to schizophrenia patients.

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Coping strategies for antidepressant side effects

Kikuchi Toshiaki, Suzuki Takefumi, Uchida Hiroyuki, Watanabe Koichiro, Mimura Masaru

Journal of Affective Disorders 143 ( 1-3 ) 89 - 94 2012.12

ISSN 0165-0327

Background: Patients coping methods to palliate side effects of antidepressants have not been reported in the literature. Methods: Through an Internet survey, 856 participants who were diagnosed with depression and receiving antidepressants were recruited to report on the methods of coping with side effects. They were asked which side effect(s) they experienced and to write freely about the way they tried to counteract these effects. We classified active coping methods into the following sub-types: adjustment of prescriptions, additional medication, complementary therapy, consultation with physicians, and daily relief. Results: The prevalence of active coping differed across side effects (from 26.7%, sexual dysfunction, to 89.5%, dry mouth). Events with a lower percentage of active coping were more likely to be managed with adjustment of prescriptions: (sexual dysfunction, 41.9%; fatigue, 36.8%; sweating, 20.0%; tremor, 42.5%; and somnolence, 31.8%). Further, a strong negative correlation was found between the percentage of participants reporting an adjustment of prescription and that reporting an active coping (r=-0.907, p<0.001). The daily relief sub-type contained a variety of strategies, including negative methods such as vomiting for nausea and weight gain and drinking alcohol for insomnia. Limitations: Sampling of subjects were biased due to an Internet survey and diagnosis of depression and experience of side effects were self-reported. Conclusion: Patients with depression use various ways in alleviating antidepressants side effects. Some effects such as sexual dysfunction and fatigue may not be amenable to subjective coping efforts and others are sometimes managed inappropriately, which warrants a prudent attention.

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Coping strategies for antidepressant side effects: An Internet survey

Kikuchi T., Suzuki T., Uchida H., Watanabe K., Mimura M.

Journal of Affective Disorders (Journal of Affective Disorders) 143 ( 1-3 ) 89 - 94 2012.12

ISSN 01650327

Background: Patients coping methods to palliate side effects of antidepressants have not been reported in the literature. Methods: Through an Internet survey, 856 participants who were diagnosed with depression and receiving antidepressants were recruited to report on the methods of coping with side effects. They were asked which side effect(s) they experienced and to write freely about the way they tried to counteract these effects. We classified active coping methods into the following sub-types: adjustment of prescriptions, additional medication, complementary therapy, consultation with physicians, and daily relief. Results: The prevalence of active coping differed across side effects (from 26.7%, sexual dysfunction, to 89.5%, dry mouth). Events with a lower percentage of active coping were more likely to be managed with adjustment of prescriptions: (sexual dysfunction, 41.9%; fatigue, 36.8%; sweating, 20.0%; tremor, 42.5%; and somnolence, 31.8%). Further, a strong negative correlation was found between the percentage of participants reporting an adjustment of prescription and that reporting an active coping (r=-0.907, p<0.001). The daily relief sub-type contained a variety of strategies, including negative methods such as vomiting for nausea and weight gain and drinking alcohol for insomnia. Limitations: Sampling of subjects were biased due to an Internet survey and diagnosis of depression and experience of side effects were self-reported. Conclusion: Patients with depression use various ways in alleviating antidepressants side effects. Some effects such as sexual dysfunction and fatigue may not be amenable to subjective coping efforts and others are sometimes managed inappropriately, which warrants a prudent attention. © 2012 Elsevier B.V.

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Deficit status in bipolar disorder: Investigation on prevalence rate and description of seven cases

Nio S., Suzuki T., Uchida H., Watanabe K., Mimura M.

Journal of Affective Disorders (Journal of Affective Disorders) 143 ( 1-3 ) 248 - 252 2012.12

ISSN 01650327

Objective: While the Kraepelinian dichotomy explicitly distinguishes between schizophrenia and bipolar disorder, it remains unclear as to whether a deficit form of bipolar disorder exists. Method: We conducted a study to investigate the prevalence rate of the deficit form of bipolar disorder; the criteria of which were basically adopted by the original proposal for schizophrenia that described the predominance of negative symptoms for over a year. Moreover, we presented a series of cases with deficit bipolar disorder to characterize its clinical pictures in detail. Results: Consecutive outpatients who visited one psychiatric hospital in Tokyo, Japan in March 2007 were evaluated cross-sectionally. Additionally, medical charts of inpatients who were hospitalized in the same hospital between April 2006 and March 2007 were also thoroughly reviewed. Of 494 patients, 7 patients (1.4%; 10.9% of 64 bipolar cases) fulfilled the criteria for bipolar disorder with deficit syndrome. Seven deficit cases had a mean±SD age of 61±5 year-old with the age at onset being 25±8 year-old. In addition to pervasive negative symptoms, they exhibited evidence of cognitive impairments close to the magnitude of what is usually noted in schizophrenia (i.e. a mean±SD total IQ score of 80±9 in the Wechsler Adult Intelligence Scale and 0.4±0.5 in the Wisconsin Card Sorting Test, categories achieved). Conclusion: Although preliminary, the evidence on deficit status in patients with bipolar disorder that we found in this study appears more consistent with recent evidence and challenges the Kraepelinian dichotomy that reserves deficit status solely to schizophrenia patients. © 2012 Elsevier B.V.

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Temperature dependence of oxygen reduction reaction activity at stabilized Pt skin-PtCo alloy/graphitized carbon black catalysts prepared by a modified nanocapsule method.

Okaya K, Yano H, Kakinuma K, Watanabe M, Uchida H

ACS applied materials & interfaces 4 ( 12 ) 6982 - 91 2012.12

ISSN 1944-8244

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Perceptual simulations can be as expressive as first-order logic.

Uchida H, Cassimatis NL, Scally JR

Cognitive processing 13 ( 4 ) 361 - 9 2012.11

ISSN 1612-4782

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自閉症スペクトラム障害のコミュニケーションの問題について　ロールシャッハ・テスト質疑段階でのやりとりを通して

内田裕之, 明翫光宜, 辻井正次

ロールシャッハ法研究 (日本ロールシャッハ学会) 16 3 - 12 2012.11

ISSN 1345-0743

本研究では、自閉症スペクトラム障害のコミュニケーションの問題について、ロールシャッハ・テストの質疑段階の特徴から分析した。ロールシャッハ・テストの質疑段階で観察されたコミュニケーション上の問題として、「説明を拒否すること」、「反応の確信・実感を主張すること」、「反応の知覚理由でなく反応概念を説明すること」、「説明しているうちに反応概念がズレてしまうこと」、「不釣り合いな認知」の5つの特徴が抽出された。これらの5つの特徴の頻度を、統合失調症群と比較した結果、これらは自閉症スペクトラム障害独自のコミュニケーションであることが示唆された。(著者抄録)

Therapeutic window for striatal dopamine D2/3 receptor occupancy in older patients with schizophrenia

Uchida Hiroyuki, Suzuki Takefumi, Graff-Guerrero Ariel, Mulsant Benoit H., Pollock Bruce G., Arenovich Tamara, Rajji Tarek K., Mamo David C.

American Journal of Geriatric Psychiatry 2012.10

ISSN 1064-7481

OBJECTIVE: In younger patients with schizophrenia, positron emission tomography (PET) studies have identified a therapeutic window of striatal dopamine D2/3 receptor occupancy of 65%-80%. This type of empirical information is not available in late life. Our primary aim was to assess the effect of changes in D2/3 relative receptor occupancy (RRO) on clinical outcomes in this population. DESIGN: Open-label intervention. SETTING: Centre for Addiction and Mental Health, Toronto. PARTICIPANTS: Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for more than 6 months. INTERVENTION: A dose reduction of risperidone of up to 40%, followed by a 3-month follow-up. MEASUREMENTS: Dopamine D2/3 RRO in dorsal putamen was assessed, using the region of interest analysis of [C]raclopride PET scans, before and after the dose reduction. Clinical assessments included the Positive and Negative Syndrome Scale and the Simpson-Angus Scale. RESULTS: Nine subjects (mean ± SD age: 58 ± 7 years; mean ± SD baseline risperidone dose: 3.4 ± 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were present in six subjects and were associated with 70% or more D2/3 RRO in the putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five subjects. Two subjects experienced a clinical worsening at 52% and at less than 50% D2/3 RRO. CONCLUSION: EPS diminished less than 70% D2/3 RRO, which suggests a lower therapeutic window for older patients with schizophrenia than that for younger patients. Although these findings have to be replicated in a larger sample, they have important implications for future drug development and clinical guidelines in late-life schizophrenia.

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Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients With Schizophrenia: A Pilot PET Study.

Uchida H, Suzuki T, Graff-Guerrero A, Mulsant BH, Pollock BG, Arenovich T, Rajji TK, Mamo DC

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 2012.10

ISSN 1064-7481

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The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy

Abbs Brandon, Achalia Rashmin M., Adelufosi Adegoke O., Aktener Ahmet Yiǧit, Beveridge Natalie J., Bhakta Savita G., Blackman Rachael K., Bora Emre, Byun M. S., Cabanis Maurice, Carrion Ricardo, Castellani Christina A., Chow Tze Jen, Dmitrzak-Weglarz M., Gayer-Anderson Charlotte, Gomes Felipe V., Haut Kristen, Hori Hiroaki, Kantrowitz Joshua T., Kishimoto Taishiro, Lee Frankie H F, Lin Ashleigh, Palaniyappan Lena, Quan Meina, Rubio Maria D., de Azúa Sonia Ruiz, Sahoo Saddichha, Strauss Gregory P., Szczepankiewicz Aleksandra, Thompson Andrew D., Trotta Antonella, Tully Laura M., Uchida Hiroyuki, Velthorst Eva, Young Jared W., O'Shea Anne, DeLisi Lynn E.

Schizophrenia Research 141 ( 1 ) 2012.10

ISSN 0920-9964

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

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The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: Summaries of oral sessions

Abbs B., Achalia R.M., Adelufosi A.O., Aktener A.Y., Beveridge N.J., Bhakta S.G., Blackman R.K., Bora E., Byun M.S., Cabanis M., Carrion R., Castellani C.A., Chow T.J., Dmitrzak-Weglarz M., Gayer-Anderson C., Gomes F.V., Haut K., Hori H., Kantrowitz J.T., Kishimoto T., Lee F.H.F., Lin A., Palaniyappan L., Quan M., Rubio M.D., de Azúa S.R., Sahoo S., Strauss G.P., Szczepankiewicz A., Thompson A.D., Trotta A., Tully L.M., Uchida H., Velthorst E., Young J.W., O'Shea A., DeLisi L.E.

Schizophrenia Research (Schizophrenia Research) 141 ( 1 ) e1 - e24 2012.10

ISSN 09209964

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. © 2012 Elsevier B.V.

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