研究者詳細 - 内田　裕之

論文 - 内田　裕之

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D2 receptor blockade by risperidone correlates with attention deficits in late-life schizophrenia

Uchida H., Rajji T.K., Mulsant B.H., Kapur S., Pollock B.G., Graff-Guerrero A., Menon M., Mamo D.C.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology） 29 （ 6 ） 571 - 575 2009年12月

ISSN 0271-0749

The negative impact of antipsychotic drugs on attention is expected to be greater in late-life schizophrenia because of the age-related changes in the dopamine receptor reserve. The objective of this study was to examine the relationship between dopamine D2 receptor blockade by risperidone and the cognitive function in late-life schizophrenia. Subjects with schizophrenia or schizoaffective disorder aged 50 or older who were receiving risperidone completed a [C]raclopride positron emission tomography scan to measure D2-binding potential in the striatum. The D2 receptor blockade by risperidone was calculated using age-corrected measures from healthy individuals and region of interest analysis of dynamic positron emission tomography data coregistered to the subjects' magnetic resonance imaging scans. Cognitive function was assessed using a battery of neuropsychological tests that included the Dementia Rating Scale-2 (DRS). Eleven subjects (mean ± SD age, 64 ± 8 years) participated in this study. The mean ± SD D2 receptor blockade was 69% ± 14% (range, 34%-80%). The age-corrected score on the attention subscale in the DRS was negatively correlated with the D2 receptor blockade. The DRS attention subscale score was lower in the subjects who experienced 74.9% or higher D2 blockade (median value, corresponding to a daily risperidone dose of >3.0 mg) than in those who did not. Although a causal attribution cannot be made in light of the cross-sectional nature of this study, the results suggest the critical importance of identifying the lowest effective dose of antipsychotic drugs in older patients with schizophrenia. Copyright © 2009 by Lippincott Williams & Wilkins.

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Predicting age-specific dosing of antipsychotics

Uchida H., Pollock B., Bies R., Mamo D.

Clinical Pharmacology and Therapeutics （Clinical Pharmacology and Therapeutics） 86 （ 4 ） 360 - 362 2009年10月

ISSN 0009-9236

Antipsychotic medications are the standard of care for both acute and maintenance treatment of schizophrenia, the latter requiring an indefinite treatment across a patients life span. However, dosing and tolerability of antipsychotics have been studied primarily in younger patients, and very limited data are available for age- and phase-specific dosing. This leaves the clinician with no guidance on dose adjustment as patients grow olderan issue of critical importance, especially in light of recent concerns about increased morbidity and mortality associated with antipsychotics. © 2009 American Society for Clinical Pharmacology and Therapeutics.

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Impacts of switching antidepressants after successful electroconvulsive therapy on the maintenance of clinical remission in patients with treatment-resistant depression

Nakajima Shinichiro, Ishida Takuto, Akaishi Rei, Takahata Keisuke, Kitahata Ryosuke, Uchida Hiroyuki, Suzuki Takefumi, Takeuchi Hiroyoshi, Nomura Kensuke, Nakagawa Atsuo, Watanabe Koichiro, Kashima Haruo

Journal of ECT 25 （ 3 ） 178 - 181 2009年09月

ISSN 1095-0680

Introduction: There is no consensus regarding whether a previously prescribed, that is, failed, antidepressant should be continued or switched after a successful electroconvulsive therapy (ECT) for the maintenance of clinical remission in patients with treatment-resistant depression (TRD). In this study, we conducted a chart review to examine impacts of the antidepressant switch after the successful ECT on 1-year outcome in patients with TRD. MATERIALS AND Methods: This retrospective chart review included inpatients with TRD (ie, those who failed to respond to adequate trials of 2 distinctly different classes of antidepressants) who showed clinical remission after ECT. Readmission rate and social functioning 6 months and 1 year after the successful ECT were compared between patients who experienced an antidepressant switch and those who continued prior regimen. Results: Twenty-eight patients (mean age, 59 years; 9 men) were followed-up for 1 year. The patients who changed antidepressants after ECT (n = 7) experienced a readmission significantly less frequent than the others (n = 21) in 1 year (0% vs 43%, P = 0.043). In addition, the former showed significantly better social contacts at 6 months (P = 0.022) and 1 year (P = 0.015). There were no significant differences in baseline characteristics between the 2 groups. Conclusions: The patients who experienced an antidepressant switch after ECT required a readmission less frequently in 1 year than those who were maintained with the same antidepressant. The findings of this preliminary study suggest that a switch to another antidepressant after successful ECT may be encouraged for the maintenance of clinical remission in patients with TRD.

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Impacts of switching antidepressants after successful electroconvulsive therapy on the maintenance of clinical remission in patients with treatment-resistant depression: A chart review

Nakajima S., Ishida T., Akaishi R., Takahata K., Kitahata R., Uchida H., Suzuki T., Takeuchi H., Nomura K., Nakagawa A., Watanabe K., Kashima H.

Journal of ECT （Journal of ECT） 25 （ 3 ） 178 - 181 2009年09月

ISSN 10950680

Introduction: There is no consensus regarding whether a previously prescribed, that is, failed, antidepressant should be continued or switched after a successful electroconvulsive therapy (ECT) for the maintenance of clinical remission in patients with treatment-resistant depression (TRD). In this study, we conducted a chart review to examine impacts of the antidepressant switch after the successful ECT on 1-year outcome in patients with TRD. MATERIALS AND Methods: This retrospective chart review included inpatients with TRD (ie, those who failed to respond to adequate trials of 2 distinctly different classes of antidepressants) who showed clinical remission after ECT. Readmission rate and social functioning 6 months and 1 year after the successful ECT were compared between patients who experienced an antidepressant switch and those who continued prior regimen. Results: Twenty-eight patients (mean age, 59 years; 9 men) were followed-up for 1 year. The patients who changed antidepressants after ECT (n = 7) experienced a readmission significantly less frequent than the others (n = 21) in 1 year (0% vs 43%, P = 0.043). In addition, the former showed significantly better social contacts at 6 months (P = 0.022) and 1 year (P = 0.015). There were no significant differences in baseline characteristics between the 2 groups. Conclusions: The patients who experienced an antidepressant switch after ECT required a readmission less frequently in 1 year than those who were maintained with the same antidepressant. The findings of this preliminary study suggest that a switch to another antidepressant after successful ECT may be encouraged for the maintenance of clinical remission in patients with TRD. © 2009 by Lippincott Williams & Wilkins.

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Dosing of antipsychotics in schizophrenia across the life-spectrum

Uchida Hiroyuki, Mamo David C.

Progress in Neuro-Psychopharmacology and Biological Psychiatry 33 （ 6 ） 917 - 920 2009年08月

ISSN 0278-5846

Age effects on dosing of antipsychotics in schizophrenia and mechanisms underlying those effects have not been well understood. The objective of this article is to review the literature regarding effects of age on antipsychotic dosing in schizophrenia and potential mechanisms underlying the age-related antipsychotic sensitivity. According to prescription surveys, age appears to have biphasic effects on prescribed antipsychotic dose. The dose increased with age through the third decade, subsequently plateaued, and decreased after the fifth decade. The first half of this inverted U-shaped relationship may be attributable to a deterioration process in the early phase of schizophrenia and the contribution of 'tachyphylaxis' of antipsychotics on the dopaminergic system. The following age-related decline in prescribed dose is likely associated with physiological aging. Recent data suggest that this increased antipsychotic sensitivity with age comes from age-related functional decline in the dopaminergic system, including endogenous dopamine level and dopamine receptor density. Although the evidence on potential mechanisms underlying age effects on antipsychotic dosing is still limited, alterations in the dopaminergic system due to aging and chronic exposure to this drug may contribute to the inverted U-shaped relationship between dose and age. This age-related antipsychotic sensitivity highlights the importance of finding the lowest possible effective dose of antipsychotic drugs as patients age to enhance therapeutic effects as well as minimize their side effects.

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Selective serotonin reuptake inhibitor-induced spermatorrhea in 2 patients

Nakajima Shinichiro, Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Kashima Haruo

Journal of Clinical Psychiatry 70 （ 8 ） 1192 - 1193 2009年08月

ISSN 0160-6689

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Predictors of clinical worsening after a switch to aripiprazole in patients with schizophrenia

Takeuchi Hiroyoshi, Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Kashima Haruo

Journal of Clinical Psychopharmacology 29 （ 4 ） 394 - 396 2009年08月

ISSN 0271-0749

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Proteomic approach for identification of protein S-nitrosation in mouse gastric mucosa treated with S-nitrosoglutathione.

Ohtake K, Shimada N, Uchida H, Kobayashi J

Journal of proteomics 72 （ 5 ） 750 - 60 2009年07月

ISSN 1874-3919

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Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT_2A) receptors in older, healthy adults

Chow Tiffany W., Mamo David C., Uchida Hiroyuki, Graff-Guerrero Ariel, Houle Sylvain, Smith Gwenn S., Pollock Bruce G., Mulsant Benoit H.

BMC Medical Imaging 9 2009年07月

Background: Position emission tomography (PET) imaging using [¹⁸F]-setoperone to quantify cortical 5-HT_2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT_2A receptor (5HT_2AR) binding potential. The purpose of this study was to assess the test-retest variability of [¹⁸F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT_2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65-78 years) completed two [¹⁸F]-setoperone PET scans on two separate occasions 5-16 weeks apart. Results: The average difference in the binding potential (BP_ND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion: We conclude that the test-retest variability of [¹⁸F]-setoperone PET in elderly subjects is comparable to that of [¹⁸F]-setoperone and other 5HT_2AR radiotracers in younger subject samples.

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Test-retest variability of high resolution positron emission tomography (PET) imaging of cortical serotonin (5HT<inf>2A</inf>) receptors in older, healthy adults

Chow T., Mamo D., Uchida H., Graff-Guerrero A., Houle S., Smith G., Pollock B., Mulsant B.

BMC Medical Imaging （BMC Medical Imaging） 9 12 2009年07月

Background: Position emission tomography (PET) imaging using [18F]-setoperone to quantify cortical 5-HT2A receptors has the potential to inform pharmacological treatments for geriatric depression and dementia. Prior reports indicate a significant normal aging effect on serotonin 5HT2A receptor (5HT2AR) binding potential. The purpose of this study was to assess the test-retest variability of [18F]-setoperone PET with a high resolution scanner (HRRT) for measuring 5HT2AR availability in subjects greater than 60 years old. Methods: Six healthy subjects (age range = 65-78 years) completed two [18F]-setoperone PET scans on two separate occasions 5-16 weeks apart. Results: The average difference in the binding potential (BPND) as measured on the two occasions in the frontal and temporal cortical regions ranged between 2 and 12%, with the lowest intraclass correlation coefficient in anterior cingulate regions. Conclusion: We conclude that the test-retest variability of [18F]-setoperone PET in elderly subjects is comparable to that of [18F]-setoperone and other 5HT2AR radiotracers in younger subject samples. © 2009 Chow et al; licensee BioMed Central Ltd.

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Persistence and compliance to antidepressant treatment in patients with depression

Sawada Norifusa, Uchida Hiroyuki, Suzuki Takefumi, Watanabe Koichiro, Kikuchi Toshiaki, Handa Takashi, Kashima Haruo

BMC Psychiatry 9 2009年06月

Background: Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods: In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period. Results: Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8). Conclusion: Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects.

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Persistence and compliance to antidepressant treatment in patients with depression: A chart review

Sawada N., Uchida H., Suzuki T., Watanabe K., Kikuchi T., Handa T., Kashima H.

BMC Psychiatry （BMC Psychiatry） 9 38 2009年06月

Background: Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods: In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period. Results: Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8). Conclusion: Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects. © 2009 Sawada et al; licensee BioMed Central Ltd.

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Strict use of terminology

Uchida Hiroyuki, Suzuki Takefumi

Psychiatry and Clinical Neurosciences 63 （ 3 ） 430 - 431 2009年06月

ISSN 1323-1316

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Clozapine exposure and the impact of smoking and gender

Ng Wenzie, Uchida Hiroyuki, Ismail Zahinoor, Mamo David C., Rajji Tarek K., Remington Gary, Sproule Beth, Pollock Bruce G., Mulsant Benoit H., Bies Robert R.

Therapeutic Drug Monitoring 31 （ 3 ） 360 - 366 2009年06月

ISSN 0163-4356

The primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, including age, gender, weight, smoking status, and dosage formulation as covariates. Pharmacokinetic parameters and interindividual and residual variabilities were estimated with 1- and 2-compartment models. A total of 519 plasma clozapine concentrations from 197 patients (138 males; mean ± SD age, 38 ± 13 years; schizophrenia spectrum disorder 98.2%) were included for the analysis. A 1-compartment model with first-order absorption and elimination best described the data. Apparent volume of distribution was fixed to a previously reported value in the literature of 7 L/kg.The population-predicted oral clearance of clozapine and norclozapine was 18.0 and 39.0 L/h, respectively; both the predicted clearance values vary nearly 6-fold (range, 9.18-59.06 and 16.29-97.84 L/h, respectively). For clozapine, smokers and males showed increased oral clearance by 6.0 and 4.5 L/h, respectively. For norclozapine, smokers and male gender were associated with an increased oral clearance of 11.3 and 7.6 L/h, respectively. The formulation of clozapine administered had an impact on the absorption rate with a Ka of 0.14/h for tablet and 10.3/h for the suspension form.The data suggest that smoking and male gender are associated with lower exposure to clozapine and norclozapine due to the higher oral clearance. These findings may account for some of the variability in clozapine exposure and have important implications for individualized drug dosing and therapeutic drug monitoring.

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Clozapine exposure and the impact of smoking and gender: A population pharmacokinetic study

Ng W., Uchida H., Ismail Z., Mamo D.C., Rajji T.K., Remington G., Sproule B., Pollock B.G., Mulsant B.H., Bies R.R.

Therapeutic Drug Monitoring （Therapeutic Drug Monitoring） 31 （ 3 ） 360 - 366 2009年06月

ISSN 01634356

The primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, including age, gender, weight, smoking status, and dosage formulation as covariates. Pharmacokinetic parameters and interindividual and residual variabilities were estimated with 1- and 2-compartment models. A total of 519 plasma clozapine concentrations from 197 patients (138 males; mean ± SD age, 38 ± 13 years; schizophrenia spectrum disorder 98.2%) were included for the analysis. A 1-compartment model with first-order absorption and elimination best described the data. Apparent volume of distribution was fixed to a previously reported value in the literature of 7 L/kg.The population-predicted oral clearance of clozapine and norclozapine was 18.0 and 39.0 L/h, respectively; both the predicted clearance values vary nearly 6-fold (range, 9.18-59.06 and 16.29-97.84 L/h, respectively). For clozapine, smokers and males showed increased oral clearance by 6.0 and 4.5 L/h, respectively. For norclozapine, smokers and male gender were associated with an increased oral clearance of 11.3 and 7.6 L/h, respectively. The formulation of clozapine administered had an impact on the absorption rate with a Ka of 0.14/h for tablet and 10.3/h for the suspension form.The data suggest that smoking and male gender are associated with lower exposure to clozapine and norclozapine due to the higher oral clearance. These findings may account for some of the variability in clozapine exposure and have important implications for individualized drug dosing and therapeutic drug monitoring. Copyright © 2009 by Lippincott Williams & Wilkins.

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Benzodiazepine and antidepressant use in elderly patients with anxiety disorders

Uchida Hiroyuki, Suzuki Takefumi, Mamo David C., Mulsant Benoit H., Kikuchi Toshiaki, Takeuchi Hiroyoshi, Tomita Masayuki, Watanabe Koichiro, Yagi Gohei, Kashima Haruo

Journal of Anxiety Disorders 23 （ 4 ） 477 - 481 2009年05月

ISSN 0887-6185

Since the literature on benzodiazepine use in elderly patients with anxiety disorders is limited, a large cross-sectional review of psychotropic prescriptions in 796 patients with neurotic disorders (ICD-10) (age range = 11-91 years) was conducted across 30 sites in Japan. Use of benzodiazepine-derivative anxiolytics was approximately 70% in all decades without a group difference. The proportion of subjects who received prescriptions for benzodiazepine-derivative anxiolytics in the absence of antidepressants was higher in older age groups (e.g., 27.7% and 43.2% in the third and sixth decades, respectively). On the other hand, antidepressants were less frequently prescribed in older age groups (e.g., 59.8% and 41.5% in the third and sixth decades, respectively). The very high use of anxiolytics in the elderly, especially in the absence of concomitant antidepressant use, is a cause for concern since they are not a preferred long-term treatment strategy given their adverse effects in the elderly.

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Benzodiazepine and antidepressant use in elderly patients with anxiety disorders: A survey of 796 outpatients in Japan

Uchida H., Suzuki T., Mamo D., Mulsant B., Kikuchi T., Takeuchi H., Tomita M., Watanabe K., Yagi G., Kashima H.

Journal of Anxiety Disorders （Journal of Anxiety Disorders） 23 （ 4 ） 477 - 481 2009年05月

ISSN 08876185

Since the literature on benzodiazepine use in elderly patients with anxiety disorders is limited, a large cross-sectional review of psychotropic prescriptions in 796 patients with neurotic disorders (ICD-10) (age range = 11-91 years) was conducted across 30 sites in Japan. Use of benzodiazepine-derivative anxiolytics was approximately 70% in all decades without a group difference. The proportion of subjects who received prescriptions for benzodiazepine-derivative anxiolytics in the absence of antidepressants was higher in older age groups (e.g., 27.7% and 43.2% in the third and sixth decades, respectively). On the other hand, antidepressants were less frequently prescribed in older age groups (e.g., 59.8% and 41.5% in the third and sixth decades, respectively). The very high use of anxiolytics in the elderly, especially in the absence of concomitant antidepressant use, is a cause for concern since they are not a preferred long-term treatment strategy given their adverse effects in the elderly. © 2008 Elsevier Ltd. All rights reserved.

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Survey of benzodiazepine and antidepressant use in outpatients with mood disorders in Japan

Uchida H., Suzuki T., Mamo D., Mulsant B., Tsunoda K., Takeuchi H., Kikuchi T., Nakajima S., Nomura K., Tomita M., Watanabe K., Kashima H.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 63 （ 2 ） 244 - 246 2009年04月

ISSN 1323-1316

Data on benzodiazepine use in mood disorders are still limited, especially among seniors. A cross-sectional review of psychotropic prescriptions in 948 outpatients with mood disorders (405 male; mean ± SD age, 52 ± 17 years; age range, 16- 91 years) was conducted in Japan. The use of benzodiazepine-derivative anxiolytics was approximately 60% in all decades, including older patients, without a group difference. The frequent use of benzodiazepines is a cause for concern because they are not preferred treatment, given their well-known adverse effects especially in the elderly. © 2009 The Authors.

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Long-term stability of measuring D₂ receptors in schizophrenia patients treated with antipsychotics

Uchida Hiroyuki, Graff-Guerrero Ariel, Mulsant Benoit H., Pollock Bruce G., Mamo David C.

Schizophrenia Research 109 （ 1-3 ） 130 - 133 2009年04月

ISSN 0920-9964

Background: While antipsychotic-free schizophrenia patients showed a high degree of within-subject variability in dopamine D₂ receptor density over 6-24 months, no study has examined the long-term stability of D₂ receptor measures in medicated patients. Methods: Four schizophrenia patients receiving a stable dose of risperidone underwent [¹¹C]raclopride positron emission tomography scans on two occasions 5-14 months apart. Results: Plasma risperidone levels were found to be consistent between scans, and consistencies of nondisplaceable D₂ binding potential and D₂ occupancy were good. Conclusions: The finding supports the validity of quantification of D₂ receptor binding in longitudinal PET studies of medicated patients with schizophrenia.

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Long-term stability of measuring D<inf>2</inf> receptors in schizophrenia patients treated with antipsychotics

Uchida H., Graff-Guerrero A., Mulsant B.H., Pollock B.G., Mamo D.C.

Schizophrenia Research （Schizophrenia Research） 109 （ 1-3 ） 130 - 133 2009年04月

ISSN 09209964

Background: While antipsychotic-free schizophrenia patients showed a high degree of within-subject variability in dopamine D2 receptor density over 6-24 months, no study has examined the long-term stability of D2 receptor measures in medicated patients. Methods: Four schizophrenia patients receiving a stable dose of risperidone underwent [11C]raclopride positron emission tomography scans on two occasions 5-14 months apart. Results: Plasma risperidone levels were found to be consistent between scans, and consistencies of nondisplaceable D2 binding potential and D2 occupancy were good. Conclusions: The finding supports the validity of quantification of D2 receptor binding in longitudinal PET studies of medicated patients with schizophrenia. © 2008 Elsevier B.V. All rights reserved.

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