Masaru Mimura

Publications (94)235.19 Total impact

• Article: Neuroanatomical abnormalities before onset of delusions in patients with Alzheimer's disease: a voxel-based morphometry study.

  Shutaro Nakaaki, Junko Sato, Katsuyoshi Torii, Mizuki Oka, Atsushi Negi, Takashi Nakamae, Jin Narumoto, Jun Miyata, Toshi A Furukawa, Masaru Mimura
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  ABSTRACT: Structural brain abnormalities associated with delusions in Alzheimer's disease are poorly understood. In addition, whether the neural substrate underlying the delusions develops before the onset of the delusions is unclear. In this study, we used a voxel-based morphometry approach to examine the existence of regional structural abnormalities at baseline in patients with Alzheimer's disease who did and who did not develop delusions. Using the Neuropsychiatric Inventory, we identified patients with Alzheimer's disease who exhibited delusions during a 2-year period. All the patients had undergone a magnetic resonance imaging examination at the start of the study period (baseline). We conducted a voxel-based morphometry analysis using statistical parametric mapping (SPM5) software and compared the results of patients with Alzheimer's disease who did and did not develop delusions. Compared with the patients who did not develop delusions (n = 35), the patients who did develop delusions (n = 18) had significantly smaller gray matter volumes on both sides of the parahippocampal gyrus, the right posterior cingulate gyrus, the right orbitofrontal cortex, both sides of the inferior frontal cortex, the right anterior cingulate, and the left insula. Structural brain abnormalities involving both the frontal and medial temporal lobes may be crucial to the expression of delusions in patients with Alzheimer's disease.
  Neuropsychiatric Disease and Treatment 01/2013; 9:1-8. · 1.81 Impact Factor
• Article: Decreased white matter integrity before the onset of delusions in patients with Alzheimer's disease: diffusion tensor imaging.

  Shutaro Nakaaki, Junko Sato, Katsuyoshi Torii, Mizuki Oka, Atsushi Negi, Takashi Nakamae, Jin Narumoto, Jun Miyata, Toshi A Furukawa, Masaru Mimura
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  ABSTRACT: The pathology of delusions in patients with Alzheimer's disease (AD) associated with white matter (WM) abnormalities is poorly understood. In addition, whether the abnormalities in WM integrity that underlie the delusions develop before the onset of the delusions remains unclear. In this study, we used a diffusion tensor imaging approach to examine the existence of baseline abnormalities in WM integrity in AD patients who developed delusions and AD patients who did not develop delusions. Using the Neuropsychiatric Inventory, we identified patients with AD who exhibit delusions during a 1-year period. All the patients underwent a magnetic resonance imaging (MRI) examination at baseline. We conducted fractional anisotropy using tract-based spatial statistics software and compared the results of AD patients who developed delusions with those who did not develop delusions. Compared with the AD patients who did not develop delusions (n = 15), the AD patients who developed delusions (n = 10) exhibited two relatively large clusters and one minimal cluster of significantly lower fractional anisotropy results. The first cluster was located in the left parieto-occipital region and included several fibers: the left inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus, the posterior corona radiate, and the forceps major of the corpus callosum. The second cluster was located on the body of the corpus callosum. A third minimal cluster was located on the superior temporal gyrus white matter. Abnormalities in WM integrity involving several fibers may be crucial to the development of delusions in AD patients.
  Neuropsychiatric Disease and Treatment 01/2013; 9:25-9. · 1.81 Impact Factor
• Article: Behavior management approach for agitated behavior in Japanese patients with dementia: a pilot study.

  Junko Sato, Shutaro Nakaaki, Katsuyoshi Torii, Mizuki Oka, Atsushi Negi, Hiroshi Tatsumi, Jin Narumoto, Toshi A Furukawa, Masaru Mimura
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  ABSTRACT: Agitated behaviors are frequently observed in patients with dementia and can cause severe distress to caregivers. However, little evidence of the efficacy of nonpharmacological interventions for agitated behaviors exists for patients with dementia. The present pilot study aimed to evaluate a behavioral management program developed by the Seattle Protocols for patients with agitated behaviors in Japan. Eighteen patients with dementia (Alzheimer's disease, n = 14; dementia with Lewy bodies, n = 4) participated in an open study testing the effectiveness of a behavioral management program. The intervention consisted of 20 sessions over the course of 3 months. The primary outcomes were severity of agitation in dementia, as measured using the Agitated Behavior in Dementia scale (ABID) and the Cohen-Mansfield Agitation Inventory (CMAI). The behavioral management program resulted in significant reductions in total scores on both the ABID and CMAI. Although both physically agitated and verbally agitated behavior scores on the ABID improved significantly, symptoms of psychosis did not improve after the intervention. The behavioral management technique may be beneficial to distressed caregivers of patients with dementia. In the future, a well designed study to develop the behavioral management program more fully is needed.
  Neuropsychiatric Disease and Treatment 01/2013; 9:9-14. · 1.81 Impact Factor
• Article: [Depression and dementia: perspectives from clinical studies].

  Shoko Nozaki, Kimio Yoshimura, Masaru Mimura
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  ABSTRACT: Abstract In this review, we present an overview of clinical studies that addressed the relationship between depression and dementia or cognitive decline. Cross-sectional studies and meta-analyses have repeatedly shown an association between late-life depression (LLD) and dementia, particularly Alzheimer's disease (AD) and vascular dementia; however, the findings of cohort studies have been inconsistent. Furthermore, studies on the association between depression with a younger age of onset and dementia have yielded inconsistent results. Regarding cognitive decline associated with LLD, several studies have reported an association between LLD and mild cognitive impairment, suggesting that depression itself can cause persistent cognitive impairment. Other studies have compared the cognitive profile between LLD and depression with a younger age of onset, but their results have been inconclusive, especially regarding the association between memory impairment and the age of onset of depression. LLD is associated with vascular change and white matter degeneration of the brain, as shown by magnetic resonance imaging (MRI). Recently, several studies reported an association between gray matter change and LLD. Studies currently in progress employ functional brain imaging methods such as single-photon emission computed tomography, functional MRI, and positron emission tomography. Clinically, it is important to understand how subtypes of depression can be defined in terms of risk of developing dementia, and to devise effective treatments. One paper explored the possibility of detecting depression associated with AD by measuring the blood Aβ40/Aβ42 levels, and other studies have suggested that symptoms of apathy and loss of interest are associated with conversion of depression to AD. Unfortunately, current antidepressants may have limited efficacy on depression with dementia; therefore, further investigation for devising methods of predicting conversion of depression to dementia and subsequent treatment is required.
  Brain and nerve = Shinkei kenkyū no shinpo 12/2012; 64(12):1387-97.
• Article: Interventions to reduce antipsychotic polypharmacy: A systematic review.

  Hideaki Tani, Hiroyuki Uchida, Takefumi Suzuki, Yasuo Fujii, Masaru Mimura
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  ABSTRACT: 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.
  Biological Psychiatry 11/2012; · 8.28 Impact Factor
• Article: [Orbitofrontal cortex and morality].

  Michitaka Funayama, Masaru Mimura
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  ABSTRACT: Abstract Research on the neural substrates of morality is a recently emerging field in neuroscience. The anatomical structures implicated to play a role in morality include the frontal lobe, temporal lobe, cingulate gyrus, amygdala, hippocampus, and basal ganglia. In particular, the orbitofrontal or ventromedial prefrontal areas are thought to be involved in decision-making, and damage to these areas is likely to cause decision-making deficits and/or problems in impulsive control, which may lead to antisocial and less moral behaviors. In this article, we focus on case presentation and theory development with regard to moral judgment. First, we discuss notable cases and syndromes developing after orbitofrontal/ventromedial prefrontal damage, such as the famous cases of Gage and EVR, cases of childhood orbitofrontal damage, forced collectionism, squalor syndrome, and hypermoral syndrome. We then review the proposed theories and neuropsychological mechanisms underlying decision-making deficits following orbitofrontal/ventromedial prefrontal damage, including the somatic-marker hypothesis, reversal learning, preference judgment, theory of mind, and moral dilemma.
  Brain and nerve = Shinkei kenkyū no shinpo 10/2012; 64(10):1121-9.
• Article: Dental conditions in inpatients with schizophrenia: A large-scale multi-site survey.

  Hideaki Tani, Hiroyuki Uchida, Takefumi Suzuki, Yumi Shibuya, Hiroshi Shimanuki, Koichiro Watanabe, Ryosuke Den, Masahiko Nishimoto, Jinichi Hirano, Hiroyoshi Takeuchi, Shintaro Nio, Shinichiro Nakajima, Ryosuke Kitahata, Takashi Tsuboi, Kenichi Tsunoda, Toshiaki Kikuchi, Masaru Mimura
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  ABSTRACT: Clinical relevance of dental caries is often underestimated in patients with schizophrenia. The objective of this study was to examine dental caries and to identify clinical and demographic variables associated with poor dental condition in patients with schizophrenia. Inpatients with schizophrenia received a visual oral examination of their dental caries, using the decayed-missing-filled teeth (DMFT) index. This study was conducted in multiple sites in Japan, between October and December, 2010. A univariate general linear model was used to examine the effects of the following variables on the DMFT score: age, sex, smoking status, daily intake of sweets, dry mouth, frequency of daily tooth brushing, tremor, the Clinical Global Impression-Schizophrenia Overall severity score, and the Cumulative Illness Rating Scale for Geriatrics score. 523 patients were included in this study (mean ± SD age = 55.6 ± 13.4 years; 297 men). A univariate general linear model showed significant effects of age group, smoking, frequency of daily tooth brushing, and tremor (all p's < 0.001) on the DMFT score (Corrected Model: F(23, 483) = 3.55, p < 0.001, R2 = 0.42) . In other words, older age, smoking, tremor burden, and less frequent tooth brushing were associated with a greater DMFT score. Given that poor dental condition has been related with an increased risk of physical co-morbidities, physicians should be aware of patients' dental status, especially for aged smoking patients with schizophrenia. Furthermore, for schizophrenia patients who do not regularly brush their teeth or who exhibit tremor, it may be advisable for caregivers to encourage and help them to perform tooth brushing more frequently.
  BMC Oral Health 08/2012; 12:32.
• Article: A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine d2 receptor occupancy during maintenance treatment in schizophrenia.

  Saeko Ikai, Gary Remington, Takefumi Suzuki, Hiroyoshi Takeuchi, Takashi Tsuboi, Ryosuke Den, Jinichi Hirano, Kenichi Tsunoda, Masahiko Nishimoto, Koichiro Watanabe, Masaru Mimura, David Mamo, Hiroyuki Uchida
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  ABSTRACT: While 65%-80% occupancy of dopamine D2 receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D2 receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D2 receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D2 receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D2 occupancy as high as over 80% at the estimated trough. More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D2 receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D2 receptor occupancy levels of ≥ 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.
  The Journal of Clinical Psychiatry 08/2012; 73(8):1147-52. · 5.80 Impact Factor
• Article: Coping strategies for antidepressant side effects: An Internet survey.

  Toshiaki Kikuchi, Takefumi Suzuki, Hiroyuki Uchida, Koichiro Watanabe, Masaru Mimura
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  ABSTRACT: 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.
  Journal of affective disorders 07/2012; · 3.76 Impact Factor
• Article: Deficit status in bipolar disorder: Investigation on prevalence rate and description of seven cases.

  Shintaro Nio, Takefumi Suzuki, Hiroyuki Uchida, Koichiro Watanabe, Masaru Mimura
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  ABSTRACT: 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.
  Journal of affective disorders 07/2012; · 3.76 Impact Factor
• Article: Residual memory dysfunction in recurrent major depressive disorder-A longitudinal study from Juntendo University Mood Disorder Project.

  Hitoshi Maeshima, Hajime Baba, Yoshiyuki Nakano, Emi Satomura, Yuki Namekawa, Naoko Takebayashi, Toshihito Suzuki, Masaru Mimura, Heii Arai
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  ABSTRACT: BACKGROUND: Depression may increase the risk of developing Alzheimer's disease. Large cohort studies have shown that recurrent depression is associated with a risk of developing dementia. Other studies have documented smaller hippocampal volume in patients with recurrent depression. It is speculative that a greater risk of developing dementia may result from a higher number of previous depressive episodes. This study compared patients with recurrent and single-episode depression in the remitted stage, and healthy controls to elucidate the impact of the number of depressive episodes on memory. METHODS: Logical memory and visual reproduction subtests of the Wechsler Memory Scale-Revised were given to 68 patients with major depressive disorder (MDD) (30 patients with a single episode and residual 38 patients with recurrent multiple episodes) and 57 healthy controls. The patients with MDD received memory assessment at the time of initial remission and at the follow-up period 3 years after remission. RESULTS: At the time of initial remission, scores of both logical memory and visual reproduction subtests were significantly lower in both patient groups compared with healthy controls. At follow-up, memory dysfunction of the single-episode group disappeared, whereas scores in the recurrent group remained significantly lower than those of the single-episode group and controls. LIMITATIONS: All patients in the present study were on antidepressant medications. CONCLUSIONS: Patients with recurrent MDD with multiple depressive episodes showed residual memory dysfunction even after 3 years of remission. Persistence of memory deficits in the recurrent depression may be a risk factor for developing dementia.
  Journal of affective disorders 07/2012; · 3.76 Impact Factor
• Article: Object relations in adolescence: a comparison of normal and inpatient adolescents.

  Hideko Sekiya, Atsushi Sato, Yoshie Sakai, Yasushi Naka, Keiko Suzuki, Haruo Kashima, Masaru Mimura
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  ABSTRACT: We aimed to study the development of object relations in adolescents and their correlation with their mothers' defense styles in inpatient and normal adolescents. We administered the Thematic Apperception Test to adolescents in the adolescent unit (junior high, n = 16; senior high, n = 22) and normal controls (junior high, n = 16; senior high, n = 16). Results were analyzed using the Complexity of Representations Scale (CRS). We administered the Defense Style Questionnaire (DSQ(40)) to the subjects' mothers (patients, n = 38; controls, n = 32) to determine whether adolescents' CRS scores correlated with mothers' DSQ scores. There was a nearly significant interaction for group-by-school-year for the children's CRS scores. In the control group, senior high school students' scores (mean [SD] = 3.52 [0.49]) were significantly higher (F [1,66] = 12.3, P = 0.001) than those of junior high school students' (mean [SD] = 3.03 [0.31]). In the patient group, no significant difference was observed between senior high and junior high. For mothers' DSQ(40), mature defense scores were significantly higher in the control group than in the patient group (mean [SD] = 10.8 [1.89] vs 9.35 [1.40] in junior high, and 11.8 [1.67] vs 9.36 [1.81] in senior high, F [1,66] = 22.1, P < 0.001, two-way ANOVA). A significant, positive correlation (r = 0.37, P = 0.04) was observed between the mothers' mature defense and the children's CRS scores in the control group only. Whatever diagnoses are provided, the problems of adolescents with non-psychotic pathologies are related to the arrest of object relations development. A patient's mother cannot employ mature mechanisms to alleviate signals of anxiety sent by her child.
  Psychiatry and Clinical Neurosciences 06/2012; 66(4):270-5. · 2.13 Impact Factor
• Article: Dopamine D2 receptor occupancy with risperidone or olanzapine during maintenance treatment of schizophrenia: A cross-sectional study.

  Yuya Mizuno, Robert R Bies, Gary Remington, David C Mamo, Takefumi Suzuki, Bruce G Pollock, Takashi Tsuboi, Koichiro Watanabe, Masaru Mimura, Hiroyuki Uchida
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  ABSTRACT: In treating schizophrenia, it has been established that 65-80% occupancy of dopamine D2 receptors optimizes therapeutic efficacy while minimizing risks of extrapyramidal symptoms. However, it is unclear as to whether it is necessary to keep D2 receptor occupancy within this therapeutic window to maintain response. In this study, daily peak and trough D2 receptor occupancy levels were estimated in clinically stable patients with schizophrenia (DSM-IV) who were receiving risperidone or olanzapine. Using two collected plasma samples, plasma antipsychotic concentrations at peak and trough were estimated with population pharmacokinetic techniques. Corresponding dopamine D2 receptor occupancy levels were then estimated, using a recently developed model. 35 subjects with stable schizophrenia completed the study (mean±SD age, 48.8±13.8years; male [N=14]; Asians [N=23], Caucasians [N=12]; risperidone [N=20] at 3.2±2.3mg/day, and olanzapine [N=15] at 9.2±4.9mg/day) between September and December 2010. 48.6% (N=17) did not achieve a continuous blockade of ≥65%. Moreover, 11.4% (N=4) did not achieve the 65% threshold at estimated peak concentrations. In conclusion, approximately half the subjects with stable schizophrenia did not achieve estimated continuous blockade of D2 receptor occupancy of ≥65%. The results suggest that sustained D2 receptor occupancy levels of ≥65% may not always be necessary for the maintenance treatment of schizophrenia.
  Progress in Neuro-Psychopharmacology and Biological Psychiatry 04/2012; 37(1):182-7. · 3.25 Impact Factor
• Article: Defining treatment-resistant schizophrenia and response to antipsychotics: a review and recommendation.

  Takefumi Suzuki, Gary Remington, Benoit H Mulsant, Hiroyuki Uchida, Tarek K Rajji, Ariel Graff-Guerrero, Masaru Mimura, David C Mamo
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  ABSTRACT: Treatment-resistant schizophrenia (TRS) has been defined mainly by severity of (positive) symptoms and response to antipsychotics derived from a relative change in the representative scales (most frequently ≥ 20% decrease in the Positive and Negative Syndrome Scale: PANSS), but these definitions have not necessarily been consistent. Integrating past evidence and real-world practicability, we propose that TRS be defined by at least two failed adequate trials with different antipsychotics (at chlorpromazine-equivalent doses of ≥ 600mg/day for ≥ 6 consecutive weeks) that could be retrospective or preferably include prospective failure to respond to one or more antipsychotic trials. In addition, our proposed criteria require both a score of ≥ 4 on the Clinical Global Impression (CGI)-Severity and a score of ≤ 49 on the Functional Assessment for Comprehensive Treatment of Schizophrenia (FACT-Sz) or ≤ 50 on the Global Assessment of Functioning (GAF) scales to define TRS. Once TRS is established, we propose that subsequent treatment response be defined based on a CGI-Change score of ≤ 2, a ≥ 20% decrease on the total PANSS or Brief Psychiatric Rating Scale (BPRS) scores, and an increase of ≥ 20 points on the FACT-Sz or GAF. While these suggestions provide a pragmatic framework for TRS classification, they need to be tested in future trials.
  Psychiatry Research 03/2012; 197(1-2):1-6. · 2.52 Impact Factor
• Article: Mental health and psychosocial support after the Great East Japan Earthquake.

  Yutaka Kato, Hiroyuki Uchida, Masaru Mimura
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  ABSTRACT: Since the Great East Japan Earthquake, Keio University School of Medicine has, at the request of the Tokyo Metropolitan Government, provided mental health and psychosocial support to those living in Soma City in Fukushima Prefecture. This report covers the types of support provided in Soma City and discusses previous studies that were used as the model for current support practice and the results gained from actual performance. Also included is a summary of the objectives that were or were not achieved for medical support compared with recommendations from previous studies. Furthermore, future directions for medical support are also discussed.
  The Keio Journal of Medicine 03/2012; 61(1):15-22.
• Article: How successful are physicians in eliciting the truth from their patients? A large-scale Internet survey from patients' perspectives.

  Norifusa Sawada, Hiroyuki Uchida, Koichiro Watanabe, Toshiaki Kikuchi, Takefumi Suzuki, Haruo Kashima, Masaru Mimura
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  ABSTRACT: How honestly patients report their symptoms and medication adherence to their physicians has not been adequately addressed in patients with depression. We therefore conducted a large-scale Internet survey in an effort to discover how successful physicians are in eliciting the truth from their patients and also to examine reasons for patients' truth-concealing behaviors. 2,354 participants who had received treatment for depression within the past year and had been diagnosed with depression by Patient Health Questionaire were identified from 323,226 registrants at the Macromill database through screening procedures. Participants were asked to complete a questionnaire regarding their treatment for depression with a special focus on patient-physician relationship. This study was conducted from December 7 to 13, 2010, in Japan. 2,020 participants successfully completed the questionnaire. Overall, 70.2% of responders reported that they had withheld the truth from their physicians. A logistic regression model found significant associations of such a behavior with female sex (95% CI, 1.15-1.74; P = .001), younger age (95% CI, 0.49-0.97; P = .030), and a lower degree of satisfaction in mutual communication (95% CI, 3.17-6.58; P < .001). 69.2% and 52.6% of the participants refrained from telling about their "daily activities" and "symptoms," respectively. Female participants were more likely to hide the facts concerning "adherence to prescribed medication" and "figures such as body temperature and weight." 31.9% of participants had discontinued the treatment without consulting their physician, which was again more frequent in females, younger persons, and those who were not satisfied with communication with their physician. While the findings obtained herein need to be replicated in other patient populations, a majority of patients with depression were reluctant to uncover the truth, which emphasizes the need for more fine-tuned suspicion among physicians about symptoms and medication adherence.
  The Journal of Clinical Psychiatry 03/2012; 73(3):311-7. · 5.80 Impact Factor
• Article: Predicting plasma concentration of risperidone associated with dosage change: a population pharmacokinetic study.

  Hiroyuki Uchida, David C Mamo, Bruce G Pollock, Takefumi Suzuki, Kenichi Tsunoda, Koichiro Watanabe, Masaru Mimura, Robert R Bies
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  ABSTRACT: Due to high interindividual variability in peripheral pharmacokinetic parameters, dosing of antipsychotics relies on clinical trial and error. This blind process of upward or downward clinical dose titration carries a risk of relapse and adverse effects in the treatment of schizophrenia. Using population pharmacokinetic methods, the authors therefore sought to predict plasma concentrations of risperidone (RIS) plus 9-hydroxyrisperidone (9-OH-RIS) before a dosage change. Two plasma samples were collected at 2 separate given time points for the measurement of RIS and 9-OH-RIS concentrations from 50 patients with schizophrenia or schizoaffective disorder maintained on risperidone (mean ± SD age = 56 ± 15 years; 39 men). After an oral risperidone dose adjustment, a third sample was collected. The plasma concentration of the third sample was individually predicted in a blinded fashion with the 2 baseline plasma concentrations before dose adjustment and clinical and demographic information, using the mixed-effects model with NONMEM that was derived from the data of the Clinical Antipsychotic Trials in Intervention Effectiveness study. The mean (95% confidence interval) prediction errors (in ng/mL) were as low as 0.0 (-1.3 to 1.4) for RIS and 1.0 (-1.1 to 3.0) for 9-OH-RIS. The observed and predicted concentrations of RIS and 9-OH-RIS were highly correlated (r = 0.96, P < 0.0001 and r = 0.92, P < 0.0001, respectively). Antipsychotic plasma concentrations can be predicted before risperidone dose adjustment. In light of the known relationship between plasma drug concentration, dopamine D2 receptor occupancy, and clinical effects, our results confirm that individualized dosing with the measurement of antipsychotic plasma concentrations has the potential for bedside clinical application.
  Therapeutic drug monitoring 02/2012; 34(2):182-7. · 2.43 Impact Factor
• Article: Aberrant sense of agency in patients with schizophrenia: Forward and backward over-attribution of temporal causality during intentional action.

  Takaki Maeda, Motoichiro Kato, Taro Muramatsu, Satoru Iwashita, Masaru Mimura, Haruo Kashima
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  ABSTRACT: Self-disturbances in schizophrenia have been explained and studied from the standpoint of an abnormal sense of agency. We devised an agency-attribution task that evaluated explicit experiences of the temporal causal relations between an intentional action and an external event, without any confounding from sense of ownership of body movement. In each trial, a square piece appeared on the bottom of a computer screen and moved upward. Subjects were instructed to press a key when they heard a beep. When the key was pressed, the piece jumped with various temporal biases. Subjects were instructed to make an agency judgment for each trial. We demonstrated that an excessive sense of agency was observed in patients with schizophrenia compared with normal controls. Moreover, patient groups had a greater tendency to feel a sense of agency even when external events were programmed to precede their action. Therefore, patients felt both forward and backward exaggerated causal efficacy in the temporal event sequence during the intentional action. Confusion in the experience of temporal causal relations between the self and the external world may underlie self-disturbances in schizophrenia.
  Psychiatry research. 02/2012; 198(1):1-6.
• Article: Dopamine D2 Receptor Occupancy and Cognition in Schizophrenia: Analysis of the CATIE Data.

  Hitoshi Sakurai, Robert R Bies, Scott T Stroup, Richard S E Keefe, Tarek K Rajji, Takefumi Suzuki, David C Mamo, Bruce G Pollock, Koichiro Watanabe, Masaru Mimura, Hiroyuki Uchida
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  ABSTRACT: Introduction:Antipsychotic drugs exert antipsychotic effects by blocking dopamine D(2) receptors in the treatment of schizophrenia. However, effects of D(2) receptor blockade on neurocognitive function still remain to be elucidated. The objective of this analysis was to evaluate impacts of estimated dopamine D(2) 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. D(2) 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 D(2) occupancy levels, on neurocognitive functions.Results:D(2) occupancy levels showed significant associations with the vigilance and the summary scores. Neurocognitive functions, including vigilance, were especially impaired in subjects who showed D(2) 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 D(2) 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.
  Schizophrenia Bulletin 01/2012; · 8.80 Impact Factor
• Article: Effects of zonisamide on tardive dyskinesia: a preliminary open-label trial.

  Yusuke Iwata, Sachiko Irie, Hiroyuki Uchida, Takefumi Suzuki, Koichiro Watanabe, Satoru Iwashita, Masaru Mimura
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  ABSTRACT: Once developed, tardive dyskinesia (TD) is a challenging condition to treat. The recent evidence has indicated that zonisamide, an antiepileptic drug indicated for partial-onset seizures, may also have beneficial effects for ameliorating dyskinesia in Parkinson's disease. However, this finding has not systematically been tested in psychiatric patients with TD associated with antipsychotic treatment. The objective of this study was to examine the efficacy, tolerability, and safety of zonisamide against TD in these patients. In this 4-week open-label study, subjects who suffered TD were given 50-100 mg/day of add-on zonisamide. Severity of TD was evaluated at the baseline and endpoint, using the Abnormal Involuntary Movement Scale (AIMS). Eleven subjects (6 females; mean±SD age, 75.5±4.7 years; schizophrenia [N=6], bipolar affective disorder [N=2], schizoaffective disorder [N=1], mental retardation [N=1], mental retardation with epilepsy [N=1]; 6 were antipsychotic free at baseline) participated in this study. The AIMS total score (mean±SD) was significantly decreased from 24.1±5.5 to 19.5±5.9, with 36.4% of the subjects (N=4) demonstrating 20% or more decrease in the AIMS total score. Treatment with zonisamide was well-tolerated and no participants dropped out prematurely. In conclusion, zonisamide may be safe and effective for the treatment of TD associated with antipsychotic treatment. These preliminary findings need to be further explored by larger well-designed trials.
  Journal of the neurological sciences 01/2012; 315(1-2):137-40. · 2.32 Impact Factor