記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

We investigated the association between remission of depressive symptoms in fluvoxamine treatment and catechol-O-methyltransferase (COMT) gene. Sixteen SNPs in the COMT gene were investigated in 123 outpatients with major depression. Three single nucleotide polymorphisms located in the 5' region were associated with remission in fluvoxamine-treated outpatients with moderate to severe depression. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.psychres.2014.04.030

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim We examined the difference between the effects of olanzapine (OLZ) and risperidone (RIS) on PR and QT intervals among patients with stable schizophrenia using a cohort analysis. Methods Twenty-one subjects treated with OLZ were enrolled in the study. Following baseline assessments, which included PR and QT intervals, OLZ was switched to RIS for each subject. The same parameters were evaluated following the switch to RIS. Results All patients who had been treated with OLZ were successfully switched to RIS. In all patients, we observed a significant decrease in PR interval (t=2.397, P=0.029) and no change in either QTc or RR interval. In female patients, the QTc interval was significantly decreased (t=3.495, P=0.008) following the switch, while in male patients, the QTc interval did not change. No patients showed a PR interval of >200ms or a QTc interval of >500ms. Conclusion OLZ treatment has a greater prolonging effect on PR and QT intervals compared with RIS. Careful attention may need to be paid to the cardiac conduction system in addition to QT prolongation during OLZ treatment.

DOI： 10.1111/pcn.12136

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE BV  

DOI： 10.1016/j.schres.2013.10.036

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AimsIn Europe and North America, schizophrenia patients treated with antipsychotic agents have a higher prevalence of obesity and metabolic syndrome compared with healthy individuals. In Japan, the prevalence of overweight/obesity in the general population is considerably lower than that in Europe and North America. The purpose of this study was to investigate the prevalence of underweight and overweight/obesity as well as laboratory data in Japanese inpatients with schizophrenia.
MethodsThe subjects were 333 inpatients with schizophrenia and 191 age- and sex-matched healthy volunteers. Overweight/obesity was defined as body mass index (BMI) 25kg/m(2), standard weight was defined as BMI18.5 to <25kg/m(2) and underweight was defined as BMI<18.5kg/m(2).
ResultsA significant difference in the prevalence of the three BMI levels was observed between schizophrenia patients and controls (P<0.001). The prevalence of underweight was significantly higher in schizophrenia patients than that in controls (P<0.001). The prevalence of hypoproteinemia (P<0.001) and of hypocholesterolemia (P<0.001) were significantly higher in schizophrenia patients than in controls. In schizophrenia patients, the prevalence of hypotriglyceridemia was significantly higher in the underweight group than in the standard weight group (P=0.003) and in the overweight/obesity group (P<0.001).
ConclusionsThe prevalence of underweight in Japanese inpatients with schizophrenia may be higher compared with that in the general population. Therefore, the physical health of inpatients should be more carefully taken into account in clinical practice.

DOI： 10.1111/pcn.12082

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prevalence of diabetes in patients with schizophrenia is 2- to 3-fold higher than in the general population. Glucose abnormalities were detected in 11.9% of Japanese schizophrenic patients in a recent cross-sectional study that included fasting glucose monitoring. However, detailed studies of glucose intolerance using the glucose tolerance test have been limited in Japanese patients with schizophrenia. We investigated the prevalence of abnormal glucose tolerance after glucose loading among Japanese inpatients with schizophrenia, with normal fasting glucose levels. METHOD: A total of 258 inpatients with schizophrenia participated in this study after giving their written informed consent. A 75-g oral glucose tolerance test was conducted in the morning after a 12-hour overnight fast. RESULTS: Among patients with normal fasting glucose, 81.3% had normal glucose tolerance, 17.3% had impaired glucose tolerance, and 1.3% were diagnosed with diabetes. CONCLUSIONS: This study showed that the frequency of impaired glucose tolerance in patients with schizophrenia with normal fasting glucose levels might be higher than in the general population. Careful monitoring and screening of patients with schizophrenia for abnormal glucose metabolism might therefore be necessary. Copyright © 2013 by Lippincott Williams &amp
Wilkins.

DOI： 10.1097/JCP.0b013e3182905775

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

9-Hydroxyrisperidone (9-OH-RIS) is an active metabolite of the antipsychotic drug risperidone (RIS). The total active moiety level, in other words the sum of the RIS and 9-OH-RIS serum levels, may be important for estimating the clinical effects of RIS treatment. However, there have been no consistent results reported regarding the relationship between cytochrome P450 (CYP) 2D6 or adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) variant alleles and 9-OH-RIS or total active moiety plasma levels. Seventy-four Japanese patients treated with RIS were examined in the present study. Steady-state plasma RIS and 9-OH-RIS were measured. The CYP2D6*5, CYP2D6*10, ABCB1 3435C&gt
T, and ABCB1 2677G&gt
T/A genotypes were detected. Multiple regression analysis showed that the dose-corrected plasma RIS levels were significantly correlated with the number of CYP2D6 variant alleles and ABCB1 3435C&gt
T genotypes, whereas the 9-OH-RIS and total active moiety levels were significantly correlated with the ABCB1 3435C&gt
T genotypes and with age. On the other hand, the ABCB1 2677G&gt
T/A genotypes did not affect plasma RIS, 9-OH-RIS, or total active moiety levels. The ABCB1 3435C&gt
T genetic polymorphism may predict plasma 9-OH-RIS and total active moiety levels. Copyright © 2013 Lippincott Williams &amp
Wilkins.

DOI： 10.1097/JCP.0b013e31828ecd52

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia. Methods Subjects were patients with schizophrenia who were treated with either OLZ (n=69), RIS (n=60), ARP (n=62), or QTP (n=31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula. Results The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p=0.002) or ARP group (p=0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p=0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p=0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p=0.007). Conclusion To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval. Copyright (c) 2013 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.2309

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Although second-generation antipsychotics (SGAs) are characterized by fewer prolactin (PRL)-related side effects compared with first-generation antipsychotics, the detailed effects of SGAs on the plasma PRL levels still remain unclear. We examined the differences in plasma PRL levels among 268 patients treated for schizophrenia with olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), quetiapine (QTP), or perospirone (PER). The participants had received antipsychotic monotherapy with stable doses of OLZ, RIS, ARP, QTP, or PER for >= 3 weeks, and fasting blood samples were drawn to examine plasma PRL levels. The differences in median plasma PRL levels in all (P<0.001), male (P<0.001) and female patients (P<0.001) among the five SGA groups were statistically significant. A stepwise multiple regression analysis showed that ARP treatment was found to contribute to lower plasma PRL level, while female sex, RIS, OLZ and chlorpromazine equivalent dose were found to contribute to a higher plasma PRL level. The median value of plasma PRL level in the RIS group was twice as much compared with that in the OLZ group, although this was not statistically significant. In this study, OLZ had a considerable effect on plasma PRL level, similar to RIS, while PER did not affect plasma PRL levels, similar to QTP. Further studies are needed to clarify the differences in plasma PRL levels among SGAs. (C) 2013 Elsevier B. V. All rights reserved.

DOI： 10.1016/j.schres.2012.12.027

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objectives There have so far been few papers studying the metabolic syndrome (MetS) prevalence rate in Japanese patients with schizophrenia. We studied the MetS prevalence rate in Japanese controls and inpatients with schizophrenia and compared the prediction factors for the occurrence of MetS. Methods The subjects were 319 inpatients with schizophrenia and 154 controls. The predictive utilities of body mass index (BMI) and the individual components of MetS for MetS diagnosis were evaluated. Results The prevalence of MetS did not differ between schizophrenia and control subjects. Subjects with schizophrenia showed higher prevalences of the MetS criteria for high-density lipoprotein cholesterol (HDL) (p<0.001) and waist circumference (WC) (p<0.001). In subjects with schizophrenia, the predictive power was found to be highest for HDL, followed by WC, BMI, triglyceride, diastolic blood pressure (BP), systolic BP and fasting plasma glucose. However, in control subjects, the predictive power was found to be highest for triglyceride, followed by WC, systolic BP, BMI, HDL, diastolic BP and fasting plasma glucose. HDL was the component most predictive of MetS in subjects with schizophrenia treated with antipsychotics. Conclusion Because, in normal clinical practice, it is difficult to obtain temporal measurements for all of the MetS criteria, measurement of HDL may be useful for predicting the MetS. Copyright (c) 2013 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.2295

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記述言語：英語  

DOI： 10.1111/pcn.12012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives There are few reports regarding quetiapine (QTP)-related QT prolongation. We examined the change in QT interval after switching from aripiprazole (ARP), olanzapine (OLZ), or risperidone (RIS) to QTP. Methods Twenty subjects treated with ARP, OLZ, or RIS were enrolled in the study. Following baseline assessments, which included QT interval and electrolytes, these three drugs were switched to QTP for each subject. The same parameters were evaluated following a switch to QTP. Results All 20 patients who had been treated with ARP, OLZ, or RIS were successfully switched to QTP. Significant increases were observed in the total mean corrected QT (QTc) interval after switching (p = 0.014). The coefficient of variation for the extent of change in QTc interval was 1.66. The mean QTc with ARP treatment was significantly increased after QTP treatment (p = 0.004). Conclusions Quetiapine might have a greater effect on QTc interval than other second-generation antipsychotics. However, because there was a considerable variability in the extent of QTc prolongation after switch to QTP, further studies are required to clarify the effect of QTP on QTc interval. Copyright © 2012 John Wiley &amp
Sons, Ltd.

DOI： 10.1002/hup.2277

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

The development of impaired glucose tolerance induced by antipsychotics (APs) is of concern as a serious adverse effect of psychiatric drug therapy. However, the mechanism by which APs cause dysfunction of the glucose-insulin response is not fully understood. Recent studies have shown that patients treated with APs for schizophrenia were more likely to exhibit impaired glucose tolerance after a glucose load compared with healthy control subjects, even if fasting glucose levels were within the reference range. To explain these findings, we hypothesized that insulin secretion is increased in schizophrenic patients treated with AP, even those normal fasting glucose (NFG) levels. Therefore, oral glucose tolerance tests were conducted in 159 Japanese inpatients with AP-treated schizophrenia and in 90 healthy subjects without schizophrenia. Plasma glucose and serum insulin concentrations were measured before (0 minute) and at 30, 60, 90, and 120 minutes after the oral glucose load. Although insulin levels at 0 minute were similar in both groups of subjects, insulin levels were significantly higher in the patients treated with AP at all times after the glucose load than in the healthy subjects. In analyses of NFG subjects, insulin levels were significantly higher in the patients treated with AP compared with the healthy subjects at all times after glucose loading. Overall, we found that insulin secretion in response to a glucose load was significantly higher in the patients treated with AP, irrespective of NFG. These results suggest that APs affect the glucose-insulin response, which may lead to subclinical insulin resistance before the onset of overt glucose intolerance.

DOI： 10.1097/JCP.0b013e3182742ea4

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1440-1819.2012.02388.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Objective: Antipsychotic-treated schizophrenia patients are susceptible to dyslipidemia. However, the results of previous studies of North American and UK populations including various races have been contradictory with regard to which lipid measure was the most affected in patients with schizophrenia taking antipsychotic agents. The aim of this study was to investigate the effect of schizophrenia patients receiving antipsychotic agents on each lipid measure in a Japanese population.
Methods: The samples included 136 control individuals and 157 patients with schizophrenia treated with antipsychotic agents. Age, gender distribution and body mass index (BMI) of the controls were matched with the patients.
Results: The high-density lipoprotein cholesterol (HDL-cholesterol) levels were significantly lower in patients than in the control subjects (P<.001). However, there were no significant differences in either the low-density lipoprotein cholesterol (LDL-cholesterol) or triglyceride levels between the patient and control groups. We performed a multiple linear regression analysis, and schizophrenia receiving antipsychotics was an independent predictor of decreased HDL-cholesterol. An increased BMI, male gender and cigarette smoking were also major predictors of a decreased HDL-cholesterol level (r(2)=0.42, P<.001).
Conclusion: At least in Japanese with schizophrenia receiving antipsychotic agents, the HDL-cholesterol levels should be closely monitored in all patients, even those who are not obese or do not smoke, to decrease their risk of cardiovascular disease. (C) 2012 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.genhosppsych.2012.04.002

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記述言語：英語   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.psychres.2012.02.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: The underlying mechanism for second-generation antipsychotic (SGA)-related glucose-lipid metabolic dysfunction is not fully understood. Recent studies have suggested a possible impact of SGAs on endocrine regulation, especially on adipocytokines. We examined the effect of each SGA on various adipocytokines in normal fasting glucose (NFG) subjects.
Method: The study population comprised 113 Japanese inpatients with schizophrenia who were treated with olanzapine, risperidone, or quetiapine, and 123 healthy control (CONT) volunteers. All of the subjects were diagnosed with NFG. Plasma concentration of adiponectin, leptin, tumor necrosis factor alpha, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were compared between the SGA and CONT groups.
Results: Second-generation antipsychotic subjects had significantly higher leptin levels in comparison to the CONT subjects. The plasma concentration of adiponectin, total cholesterol, and high-density lipoprotein cholesterol in the SGA subjects were significantly lower than those in the CONT subjects. There were no significant differences in tumor necrosis factor alpha, triglyceride, and low-density lipoprotein cholesterol levels between the 2 groups. In a stepwise multiple regression analysis, olanzapine was found to be a factor that contributed to decreased adiponectin levels, And the CONT subjects were detected to be a factor associated with lower leptin levels.
Conclusions: The present study indicates the possibility that the administration of SGAs may affect adipocytokines in the NFG stage, excluding the impaired fasting glucose group, which is in the transition stage into diabetes mellitus.

DOI： 10.1097/JCP.0b013e3182524393

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1440-1819.2012.02338x

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記述言語：英語   出版者・発行元：WILEY-BLACKWELL  

DOI： 10.1111/j.1440-1819.2012.02321.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Most antipsychotic agents can cause QT prolongation, which causes torsades de pointes. The QT interval in healthy subjects is longer during nighttime than during daytime. The QT interval of patients treated with antipsychotics may be prolonged during nighttime, and the effects of antipsychotics on the QT interval may differ between antipsychotics. This study investigated the circadian dynamics of the QT interval in patients treated with antipsychotics and healthy controls, using a 24-hour Holter electrocardiogram in a clinical setting. Sixty-six patients with a diagnosis of schizophrenia that were treated with risperidone or olanzapine and 40 healthy volunteers were enrolled. The QT intervals were corrected using the Fridericia formula (QTcF = QT / RR1/3). Mean +/- SD nighttime QTcFs were 411.6 +/- 29.0, 395.9 +/- 21.2, and 387.8 +/- 19.0 milliseconds (ms) in the risperidone, olanzapine, and control groups, respectively. The mean daytime QTcFs were 397.7 +/- 23.4, 392.4 +/- 18.9, and 382.6 +/- 17.3 ms, respectively. The mean nighttime QTcF of the risperidone group was significantly longer than that of the olanzapine and control groups, although there was no significant difference in the mean daytime QTcF between the risperidone and olanzapine groups. The current study used 24-hour Holter electrocardiograms to reveal significantly longer QT intervals in the risperidone group especially during nighttime. In clinical practices, evaluations of the QT interval have been conducted over short periods in the daytime, but it is believed that such methods may not be able to fully elucidate the effects of antipsychotics on the QT interval.

DOI： 10.1097/JCP.0b013e31823f6f21

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Objective The sum of the serum levels of risperidone (RIS) and 9-hydroxyrisperidone (9-OH-RIS), which is the active moiety serum level, could be important for estimating the clinical effects of RIS. However, there have been no consistent results reported about the relationship between cytochrome P450 (CYP) 2D6*10 allele and plasma 9-OH-RIS or active moiety levels. We investigated the effect of the number of CYP2D6*10 alleles on steady-state plasma RIS, 9-OH-RIS, and active moiety levels in Japanese patients. Methods Steady-state plasma RIS, 9-OH-RIS, and active moiety levels were measured in 64 patients treated with an average dosage of 4.6 mg/day. Results The number of CYP2D6* 10 alleles significantly affected dose-corrected plasma RIS levels (p = 0.001), and the median concentrations in ng/ml/mg were 0.94 (0 allele) vs. 1.73 (1 allele) vs. 3.05 (2 alleles). The number of CYP2D6* 10 alleles did not affect plasma 9-OH-RIS or active moiety levels. Conclusion The present study shows that the number of CYP2D6* 10 alleles affected plasma RIS levels but not plasma 9-OH-RIS and plasma active moiety levels. Because the plasma active moiety levels can influence antipsychotic effects or side effects, the genetic screening of the CYP2D6* 10 allele for RIS in Asian populations may not be clinically important. Copyright (C) 2012 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.1260

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective A dose-dependent increase in risk of sudden cardiac death for the antipsychotic drug risperidone was reported. However, few reports have so far addressed QT prolongation associated with the use of risperidone or its major active metabolite, which is also used as a separate antipsychotic drug, paliperidone. Methods The present study evaluated associations between risperidone metabolism and QT interval in 61 psychiatric patients who had been receiving risperidone for >= 4 weeks at an average dosage of 4.7 mg/day. Plasma risperidone and paliperidone levels were measured and electrocardiographic measurements were also obtained. Results There was no correlation between risperidone dosage and QTc or plasma risperidone levels and QTc. However, there was a significant positive correlation between plasma paliperidone levels and QTc (r = 0.361; p = 0.004). There was no correlation between age and dose-corrected plasma risperidone levels or between age and QTc. There was a significant positive correlation between age and dose-corrected plasma paliperidone levels (r = 0.290; p = 0.023). Conclusion Clinically, paliperidone is considered to play a more important role in QT prolongation than risperidone. Copyright c 2011 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.1258

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1097/JCP.0b013e318221e80d

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objectives There have been few reports regarding olanzapine (OLZ)-related QT prolongation and hyperprolactinemia. This study evaluated the dose-dependent effect of OLZ on QT interval and plasma prolactin (PRL) level in a single sample of patients with schizophrenia.
Methods Twenty-six subjects treated with varying starting doses of OLZ were enrolled in the study. Following baseline assessments, which included completion of the Brief Psychiatric Rating Scale (BPRS), measurements of Body Mass Index (BMI), QT interval, electrolytes, fasting plasma glucose, PRL, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL), the dose of OLZ was increased for each subject. The same parameters were evaluated following the increased dose treatment.
Results A significant decrease was observed in BPRS score (p=0.01) following treatment with an increased dose of OLZ. Significant increases were observed in BMI (p=0.032), QTc (p=0.031), and plasma PRL level (p=0.028). The mean values of electrolytes, fasting plasma glucose, HbA1c, TC, TG, HDL and LDL treatment were unchanged by the switch to increased-dose OLZ treatment.
Conclusion We have demonstrated the dose-dependent effect of OLZ on the QT interval and the plasma PRL level of patients with schizophrenia. Copyright (C) 2011 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.1218

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS LTD  

The CYP2D6 enzyme is a capacity-limited high-affinity drug elimination pathway that metabolizes numerous psychiatric medicines. The capacity-limited nature of this enzyme suggests that drug dose may serve as an important factor that influence genotype-phenotype associations. However, dose dependency of CYP2D6 genotype contributions to drug elimination, and its interaction with environmental factors (e. g., smoking) did not receive adequate attention in translational study designs. Fluvoxamine is a selective serotonin reuptake inhibitor antidepressant. Fluvoxamine concentration is one of the factors previously linked to clinical remission in moderate to severe depression. We investigated the joint effect of smoking (an inducer of CYP1A2) and CYP2D6 genotype on interindividual variability in fluvoxamine steady-state concentration. Fluvoxamine concentration was measured in 87 patients treated with 50, 100, 150 or 200 mg/d. While CYP2D6 genotype significantly influenced fluvoxamine concentration in all four dose groups (p < 0.05), the percentage variance explained (R(2)) by CYP2D6 decreased as the dose of fluvoxamine increased. Smoking status (nonsmokers vs. smoking 20 or more cigarettes/d) significantly affected fluvoxamine concentration in the 50 mg/d group only (p = 0.005). Together, CYP2D6 genotype and smoking status explained 23% of the variance in fluvoxamine concentration but only at the low 50 mg/d dose group. These findings contribute to evidence-based and personalized choice of fluvoxamine dose using smoking status and CYP2D6 genetic variation. Additionally, these data lend evidence for drug dose as an important variable in translational pharmacogenetic study design and pharmaceutical phenotype associations with capacity-limited drug metabolism pathways such as CYP2D6.

DOI： 10.1177/0269881110370504

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

DOI： 10.1038/mp.2010.37

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.pnpbp.2010.10.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective We examined whether discontinuation and the responses to fluvoxamine (FLV) administration could predict the subsequent discontinuation and the responses to paroxetine (PRX) in patients with depression.
Methods The subjects comprised 106 outpatients who were diagnosed with depression, and clinical evaluation was conducted every 2 weeks. Patients who discontinued FLV because of side effects or did not achieve remission with 200 mg/day of FLV, the drug was switched to PRX. The maximum dose of PRX was 40 mg/day.
Results Among 10 patients who discontinued FLV, PRX was also discontinued in one patient. Of 33 patients without remission on FLV, PRX was discontinued because of side effects in two patients. There was no statistical difference in the discontinuation rates between the two groups. Four of 10 patients who discontinued FLV achieved remission, while nine of 33 patients without remission with FLV achieved remission with PRX. The remission rate was not significantly different between the two groups.
Conclusion Discontinuation and the responses related to FLV could not serve as a predictor for the subsequent discontinuation and the responses related to PRX. Copyright (C) 2010 John Wiley & Sons, Ltd.

DOI： 10.1002/hup.1147

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Background. Risperidone (RIS) has the highest propensity to elevate plasma prolactin (PRL) levels. While the active metabolite 9-hydroxy-rispendone (9-OH-RIS) plays a predominant role in the efficacy and side effects of RIS, the mechanistic details are still poorly understood The present study evaluated the gender differences in the relationship between plasma levels of RIS or 9-OH-RIS and PRL
Methods Twenty-one male and 19 female subjects treated with RIS were enrolled in the present series All patients had been receiving RIS for at least 4 weeks at an average dosage of 47 mg/day Plasma RIS, 9-OH-RIS and PRL levels were measured
Results. In the male patients, there was no correlation between the RIS dosage and plasma PRL levels. between plasma RIS levels and PRL levels, or between the plasma 9-OH-RIS levels and PRL levels In the female patients, there was a significant positive correlation between the plasma 9-OH-RIS levels and PRL levels (rs = 0 456, p =0 049) There was a trend toward a significant positive correlation between the RIS dosage and plasma PRL levels There was no correlation between the plasma RIS levels and PRL levels
Conclusion. 9-OH-RIS is considered to play a more important role in PRL elevation than RIS, and a gender difference exists in the effect of 9-OH-RIS on PRL level. (C) 2010 Elsevier Inc. All rights reserved

DOI： 10.1016/j.pnpbp.2010.07.003

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

Background: Perospirone was developed in Japan and is used for the treatment of schizophrenia and related illnesses. The authors investigated the relationship between the dosage of perospirone and the plasma levels of perospirone and its active metabolite, ID15036, and also evaluated the impact of the plasma concentrations of perospirone and ID15036 on the plasma prolactin level to examine whether perospirone or ID15036 affected the dopamine D(2) blockade, in psychiatric patients treated with perospirone.
Methods: The subjects consisted of 21 adults treated with perospirone (4-60 mg/day). The plasma perospirone and ID15036 levels were measured in 21 patients and serum prolactin levels were investigated in 10 male patients with schizophrenia.
Results: The plasma ID15036 level was higher than the plasma perospirone, and a positive correlation was observed between the dosage of perospirone and the ID15036 levels (p = 0.032). The 10 male patients showed a positive correlation between the plasma perospirone levels and plasma prolactin levels (r = 0.688, p = 0.028) and between the plasma ID15036 levels and prolactin levels (r = 0.775, p = 0.009).
Conclusion: The plasma levels of ID15036 may have a greater impact on the dopamine D(2) blockade than perospirone in patients treated with perospirone. (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pnpbp.2010.03.027

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DOI： 10.1016/j.pscychresns.2010.04.015

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.pnpbp.2010.04.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Gene expression profiling with microarray technology suggests that peripheral blood cells might be a surrogate for postmortem brain tissue in studies of schizophrenia. The development of an accessible peripheral biomarker would substantially help in the diagnosis of this disease. We used a bioinformatics approach to examine whether the gene expression signature in whole blood contains enough information to make a specific diagnosis of schizophrenia. Unpaired t-tests of gene expression datasets from 52 antipsychotics-free schizophrenia patients and 49 normal controls identified 792 differentially expressed probes. Functional profiling with DAVID revealed that eleven of these genes were previously reported to be associated with schizophrenia, and 73 of them were expressed in the brain tissue. We analyzed the datasets with one of the supervised classifiers, artificial neural networks (ANNs). The samples were subdivided into training and testing sets. Quality filtering and stepwise forward selection identified 14 probes as predictors of the diagnosis. ANNs were then trained with the selected probes as the input and the training set for known diagnosis as the output. The constructed model achieved 91.2% diagnostic accuracy in the training set and 87.9% accuracy in the hold-out testing set. On the other hand, hierarchical clustering, a standard but unsupervised classifier, failed to separate patients and controls. These results suggest analysis of a blood-based gene expression signature with the supervised classifier, ANNs, might be a diagnostic tool for schizophrenia. (C) 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.schres.2009.12.024

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

When predicting the effects of medication for psychiatric diseases and their side effects based on genetic information, there are many things to consider besides just genetic information, including the index to be evaluated. We have shown before that it is important to simultaneously analyze both pharmacokinetic factors such as the blood concentration and pharmacodynamic factors such as the site of drug action, when searching for genetic information that can be used to predict the treatment effects of fluvoxamine for depression and its side effects. For example, we have shown that there exists a specific concentration that can be used to predict remission in the treatment of depression with fluvoxamine (Fukui et al, 2008)
however, it is considered that without a sufficient examination of such factors besides genetic information, it is difficult to predict the effects using just genetic information. On the other hand, the situation is more complex with medication for schizophrenia. Although it appears that consensus has been obtained in that the goal of medication for depression is remission, the goal of medication for schizophrenia is not clear and it cannot be said that prediction studies on the effects have been sufficiently conducted using genetic information. Therefore, at our facility, focusing on metabolic anomalies due to antipsychotics, QT prolongation, and hyperprolactinemia, which have become issues in recent years, a prediction study on side effects was conducted. Because such side effects can be quantified, in comparison with the effects study, it is advantageously simple to examine the relationship with genetic information. However, in the course of this study, we discovered that there was a gender difference in terms of glycolipid metabolic anomalies, that antipsychotics particularly extended the QT interval during nighttime, and that prolactine following the administration of antipsychotics temporally increased before declining again a few weeks later. We believe that when examining the relationship between side effects and genetic information, the genetic information may not be sufficiently utilized unless the analysis is performed after obtaining a better understanding of the characteristics of such side effects.

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DOI： 10.1136/bmj.a1792

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Several studies have reported that the cytochrome P450 (CYP) 2D6 plays all important role ill the fluvoxamine metabolism. However, some other studies have reported that the CYP2D6 genotype has no major impact on the fluvoxamine concentration. This Study investigated the close-dependent effect of CYP2D6-variant alleles oil the steady-state fluvoxamine concentration. There were 23 patients whose plasma concentrations Of fluvoxamine were measured at 4 doses (50, 100, 150, and 200 mg/d). The differences in the plasma fluvoxamine concentration were analyzed between 2 genotype groups divided by the number of CYP2D6-variant alleles (with 0 and 1 or 2 variant alleles). The results demonstrated the nonlinear kinetics Of fluvoxamine metabolism, and the degree of nonlinear kinetics decreased as the dose was increased. Significant differences in fluvoxamine concentration were observed between the subjects with 0 variant alleles and the Subjects with 1 or 2 variant alleles (P = 0.044) when they were treated by 50 mg of fluvoxamine. There were no significant differences in the plasma concentration of fluvoxamine at 100, 150, and 200 mg/d. The present study suggests that the effect of the CYP2D6 genotype oil fluvoxamine metabolism is greater at lower closes of fluvoxamine.

DOI： 10.1097/FTD.0b013e31818d73b3

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記述言語：英語   出版者・発行元：LINGUISTIC SOC AMER  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Therapeutic drug monitoring studies of selective serotonin reuptake inhibitor (SSRI) antidepressants thus far failed to identify a clear concentration-response relationship in major depression. Majority of the previous studies defined clinical response as 50% or greater reduction from baseline in depression rating scale scores. Because many patients who meet these criteria still present symptoms associated with functional impairment, there is a need to consider "remission" as an alternative end point in concentration-response analyses of SSRIs. The present 12-week prospective study investigated the relationship between fluvoxamine (an SSRI) plasma concentration and remission in outpatients with depression. We used a flexible dose titration study designed to mimic clinical practice within the therapeutic dose range of fluvoxamine (25-200 mg/d). Receiver operating characteristics (ROC) curve was computed to determine the optimal fluvoxamine plasma concentration for remission using 269 concentration data obtained from 80 patients. Analysis of the ROC curve from the entire study sample did not reveal a fluvoxamine concentration significantly predicting remission. By contrast, ROC analysis specifically in patients with moderate to severe depression (N = 51; baseline 17-item Hamilton Rating Scale for Depression score >= 20) found a fluvoxamine concentration of 61.4 ng/mL as a significant predictor of remission. In conclusion, therapeutic drug monitoring may be useful for rational titration and individualization of fluvoxamine dose and predicting remission in patients with moderate to severe depression, who may presumably display lesser placebo component in pharmacodynamic response.

DOI： 10.1097/JCP.0b013e3181730850

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotrophic cytokine and exerts neuroprotective and neurodegenerative effects in brain, Several studies have indicated that TNF-alpha is likely related to the pathogenesis of schizophrenia. Recent genetic investigations have revealed that a TNF-alpha gene promoter polymorphism (-G308A) is associated with schizophrenia, although negative findings have also been reported. To assess whether the TNF-alpha gene promoter variants including -G308A could be implicated in vulnerability to schizophrenia, we conducted a case-control association analysis (265 cases and 424 controls) and the transmission disequilibrium test (TDT) analysis (83 trios) for four polymorphisms (-G238A, -G308A, -C857T and -T1031C) in Japanese subjects. In a case-control analysis, there was no significant association between the promoter polymorphisms or haplotypes in the TNF-alpha gene and schizophrenia. In the TDT analysis, we also did not observe transmission distortion. Our results suggest that the above four polymorphisms in the promoter region of the TNF-alpha gene appear not to confer increased susceptibility for schizophrenia in a Japanese population. (C) 2006 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.psychres.2006.03.009

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

This study investigated effects of the 3435 C > T genotype of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1, MDR1) gene on the steady-state plasma concentration of fluvoxamine (FLV).
Methods: Sixty-two psychiatric patients were treated with different doses (50, 100, 150, and 200 mg/d) of FLV. Blood samples were collected after at least 2 weeks of treatment with the same daily dose to obtain steady-state concentrations of FLV, and 3435 C > T genotype was determined by polymerase chain reaction.
Results: FLV concentration-to-dose ratio was significantly different among 3435 C > T genotype groups at the 200 mg/d dose (P = 0.019). A post-hoc analysis revealed that FLV concentration-to-dose ratio was significantly higher in the TT genotype group as compared with the CC genotype group at the 200 mg/d dose (median value of concentration-to-dose ratio (ng/mL)/(mg/d), 0.861 vs 0.434, P = 0,026). FLV concentration-to-dose ratio was significantly higher in the CT + TT genotype group than the CC genotype group at the 200 mg/d dose (median value of concentration-to-dose ratio (ng/mL)/(mg/d), 0.618 vs 0.434, P = 0.031). At 50, 100, and 150 mg/d dose, FLV concentration-to-dose ratios were not significantly different among 3435 C > T genotype groups. At 50, 100, and 150 mg/d dose, no significant differences were found in FLV concentration-to-dose ratios between the CT + TT genotype group and CC genotype group.
Conclusions: This study suggests that pharmacokinetics of FLV depend on ABCB1 gene polymorphism only at the 200 mg/d dose.

DOI： 10.1097/FTD.0b013e318038d835

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

There is cumulative evidence that neuregulin I (NRG1) is a susceptibility gene for schizophrenia. Postmortem studies on brains from schizophrenia patients have revealed changes in the mRNA expression levels of v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (ERBB3), one of the NRG1 receptor genes. These observations suggest that NRG1-ERBB signaling is involved in the pathogenesis of schizophrenia. To assess whether the ERBB3 gene could be implicated in vulnerability to schizophrenia, we conducted a case-control (399 patients and 438 controls) association study in Japanese subjects. There were no significant association between the polymorphisms or haplotypes of ERBB3 and schizophrenia. The present study shows that ERBB3 does not play a major role in conferring susceptibility to schizophrenia in the Japanese population. (c) 2007 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2007.01.001

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記述言語：英語   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2007.06.1248

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記述言語：英語  

DOI： 10.1016/j.pnpbp.2006.05.01

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

The functional promoter polymorphism -116C/G of the X-box binding protein 1 (XBP1) gene was found to be associated with schizophrenia in Han Chinese and Japanese subjects, although contradictive negative findings were also reported in European populations. To confirm this association in a Japanese population, the authors conducted a case-control association study. There was no significant difference in both genotype and allele frequencies between the patients and control subjects, suggesting that the XBP1 -116C/G polymorphism might not confer increased susceptibility for schizophrenia in a Japanese population. However, further studies using a larger sample with detailed clinical data should be performed in several populations.

DOI： 10.1111/j.1440-1819.2006.01570.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Schizophrenia is a complex genetic disorder and affects approximately 1% of the population worldwide. Recently, Stefansson et al. identified neuregulin 1 (NRG1) on 8p12 as a susceptibility gene for schizophrenia in the Icelandic population. It was reported that the at-risk haplotype ("HapICE") constructed from five SNPs and two microsatellite markers was found to be over-represented in patients with schizophrenia compared to controls. Since then several independent studies have supported the association of NRG1 with schizophrenia. We performed a case-control association study using the four SNPs in a Japanese sample. We genotyped three SNPs (SNP8NRG221533, SNP8NRG241930, and SNP8NRG243177) from Stefansson et al. and one SNP (rs1081062) located in intron 1 of NRG1. There were no significant differences in allele frequencies for each SNP between cases and controls, however, homozygotes of minor alleles in SNP8NRG241930, SNP8NRG243177, and rs1081062 were associated with an increased risk of schizophrenia (P = 0.025, OR = 4.14; P = 0.041, OR = 1.43; and P = 0.0023, OR = 3.06, respectively). Furthermore, the haplotype constructed from four SNPs shows a significant association with schizophrenia (permutation P = 0.026). Our data support the hypothesis that NRG1 gene is a susceptibility gene for schizophrenia. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2005.11.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Aquaporin 4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. Several genome scan studies for schizophrenia found a suggestive linkage on 18q, where human AQP4 (18q11.2-12.1) is located nearby. A case-control study was performed which comprised 261 schizophrenia subjects and 278 controls from the Japanese population with four SNP markers. We found strong linkage disequilibrium (LD) and an LD block in the AQP4 gene but found no association between AQP4 and schizophrenia, both single SNP and haplotype analyses. The present study shows that AQP4 is not directly associated with schizophrenia in these Japanese patients.

DOI： 10.1111/j.1440-1819.2005.01420.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Epidermal growth factor (EGF) signal regulates the development of dopaminergic neurons and monoamine metabolism. It is suggested that EGF protein levels are decreased in the brain and blood of patients with schizophrenia. A recent study has reported that a polymorphism in EGF gene (rs4444903) is associated with schizophrenia in Finnish men. To confirm this association for another population in larger samples, we conducted a case-control association study on a Japanese population (337 cases and 421 controls). No significant difference was observed in both the allelic and genotype distribution between cases and controls in women, men and total samples. Our results suggest that the polymorphism in EGF gene might not confer increased susceptibility for schizophrenia in a Japanese population. (c) 2005 Lippincott Williams E Wilkins.

DOI： 10.1097/00001756-200503150-00019

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記述言語：日本語   出版者・発行元：(一社)日本認知症学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00990&link_issn=&doc_id=20180209010005&doc_link_id=%2Fdg3nigta%2F2017%2Fs13109%2F001%2F0551-0551%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2017%2Fs13109%2F001%2F0551-0551%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(株)星和書店  

精神疾患に不眠は高頻度で認められ、その不眠が、精神疾患の再発・再燃のリスク因子になることや、直接、社会機能や認知機能の低下に関係することも知られている。また、身体的にも様々な影響があるとされ、とくにメタボリックシンドロームのリスクになることも報告されている。したがって、精神疾患に伴う不眠に適切に対応することが求められている。そのための精神科薬物治療の向上には、睡眠に関する研究のさらなる蓄積が必要である。実際の臨床では、(1)精神疾患そのものと関連する睡眠変化、(2)治療に用いられる向精神薬と関連する睡眠変化、この両者が複雑に絡み合った状態を観察していることになる。よって臨床研究においても、睡眠評価法として確立されている終夜睡眠ポリグラフィの利用に加え、診断、症状・副作用評価、用法・用量の設定、薬物血中濃度、併用薬など臨床精神薬理学の視点に立ったデータ収集と解析が重要である。(著者抄録)

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00990&link_issn=&doc_id=20170707020009&doc_link_id=%2Fdg3nigta%2F2017%2Fs13102%2F003%2F0122-0123%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2017%2Fs13102%2F003%2F0122-0123%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(株)星和書店  

統合失調症の突然死という表現型そのものを対象とした遺伝的研究はほとんどない。しかし、その突然死の大半は心筋梗塞によるものと報告されており、心血管疾患およびその危険因子である糖・脂質代謝異常や肥満を対象とした遺伝的研究は比較的多い。最近は、内科領域などの大規模GWASによって糖・脂質代謝異常、肥満などと関連する遺伝子領域が同定されている。これらの遺伝的要因に、抗精神病薬内服および統合失調症と関連するライフスタイルなどの環境要因が加わると、交互作用によって心血管疾患および突然死のリスクがさらに高まる可能性がある。また以前より、統合失調症と糖尿病の間に共通の遺伝的要因が存在することが示唆されているが、統合失調症および統合失調症で問題となる身体リスクの双方に関連する遺伝的要因を探るという研究手法も有望と考えられる。(著者抄録)

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(公財)臨床薬理研究振興財団  

GIPR遺伝子rs10423928多型別にオランザピン内服統合失調症のAA+AT群、TT群、健常対照のAA+AT群、TT群の4群間で唯一有意差があったのは、糖負荷後30分のインスリン値で、統合失調症のAA+AT群で他群より有意に高かった。未治療・他剤内服中の統合失調症患者をGIPR遺伝子rs10423928多型別にAA+AT群、TT群に分け、オランザピン開始・オランザピンへの切り替え後4週間のBMI変化量は、AA+AT群1.2、AT群0.5と有意差を認めた。抗精神病薬内服中の統合失調症群と健常対照群の比較では、ウエスト径が統合失調症群で、空腹時血糖値は健常対照群で有意に高値であった。GIP遺伝子-1920G/A多型で分けた統合失調症のAA群ではAG+GG群に比べBMI、ウエスト径が有意に高値であり、健常対照のAA群、AG+GG群間で有意差はなかった。オランザピン内服で認めたダンピング症候群、糖負荷時インクレチン過剰分泌がクエチアピンへ変更後に改善した1例を報告した。

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(株)星和書店  

新規の抗精神病薬や抗うつ薬が登場し、統合失調症やうつ病の薬物療法の選択肢は飛躍的に増えたため、副作用モニタリングの対象や方法も大きく変化してきている。副作用モニタリングは、(1)副作用による身体リスク、(2)副作用による治療中断、を減らすという重要な役割を持っている。「副作用による身体リスク」には、短期間で生命に危険が及ぶものと、長期にわたる経過の中で死亡率の増加につながるものがある。前者は従来から注目されており、モニタリングや対処法は比較的確立していると考えられる。一方で、「長期にわたる経過の中で死亡率の増加につながる副作用」に関しては、認知・注目度が低いというのが臨床現場の実状であり、その代表的なものとして、抗精神病薬による体重増加・肥満、糖・脂質代謝異常などの代謝性副作用が挙げられる。統合失調症患者の平均寿命が一般人口と比べて短いということの背景に、この代謝性副作用の存在が指摘されている。本稿では、当施設の研究結果を示しながら、抗精神病薬の代謝性副作用に対するモニタリングをどのように行っていくべきかを中心に概説する。(著者抄録)

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

DOI： 10.3999/jscpt.43.151

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

DOI： 10.3999/jscpt.42.197

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：英語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：日本臨床精神神経薬理学会・日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)星和書店  

うつ病治療において、最初のSSRIを副作用で中断した場合、次の治療を別のSSRIで安全に行えるかについては不明である。本研究では、fluvoxamine(FLV)を副作用で中断した症例をparoxetine(PRX)へ置換し、同一個体において忍容性の違いを検討した。対象は大うつ病性障害と診断された外来患者94例。初診後FLVで治療開始し、経過中にFLVを副作用で中断した症例をPRXへ置換し、副作用による中断の有無を検討した。94例中、FLVを副作用で中断したものは10例(10.6%)であり、そのうち7例が消化器系症状で中断していた。この10例のうち、PRXも副作用で中断したものは1例(10%)であり、FLVとPRXの副作用中断の割合に統計学的有意差を認めなかった(p=1.000)。よって、うつ病治療においてFLVを副作用で中断した場合でも、PRXへの切り替え治療は安全に行える可能性が示唆された。(著者抄録)

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記述言語：日本語   出版者・発行元：(公財)臨床薬理研究振興財団  

抗うつ薬に関する薬物動態学的因子および薬理力学的因子を包括的に検討し、個々の症例に合わせた個別化抗うつ薬治療を実現するための科学的根拠を確立した。SSRIであるフルボキサミンの血中濃度に影響を与える因子、フルボキサミン血中濃度とうつ病の寛解との関係、フルボキサミン治療によるうつ病の寛解とCOMT遺伝子多型との関係について検討した。フルボキサミン用量が増加するにつれてCYP2D6遺伝子型がフルボキサミン血中濃度に与える影響が小さくなった。一日のフルボキサミン内服用量が低いほどCYP2D6遺伝子型および喫煙がフルボキサミン血中濃度に強い影響を持つことが示唆された。P2プロモーター領域rs2075507のT(A)アリルとうつ病の寛解との間に強い関連を認めた。高いCOMT活性、すなわち低ドパミン状態の方がフルボキサミン治療で寛解しやすかった。

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記述言語：日本語   出版者・発行元：(一社)日本神経精神薬理学会  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

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記述言語：日本語   出版者・発行元：(株)星和書店  

非定型抗精神病薬の浸透とともに、錐体外路症状以外にも糖・脂質代謝異常、高プロラクチン血症、QT延長といった抗精神病薬の副作用への注目が高まってきている。これらの副作用はいずれも患者のQOL低下やアドヒアランスの低下、死亡率の増加に繋がるため、その軽減に努めなければならないが、その出現頻度、重症度は個体差が大きく予測は困難である。現在、年齢、性差等の背景因子とともに、ドパミンD2受容体、ドパミンD3受容体といった神経伝達物質受容体の遺伝子多型を中心に薬理遺伝学的研究が進められているが、これまでのところ明確な結論は出ていない。今後はさらに大規模な薬理遺伝学的研究が進められ、薬剤選択や投与量への科学的指針を得ることが期待される。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(株)世論時報社  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)星和書店  

Paroxetine(PRX)とnortriptyline(NT)はチトクロームP450(CYP)2D6によって主に代謝され、PRXは強いCYP2D6阻害作用を有する。今回我々は、PRX30mg/日とNT100mg/日の併用時に振戦が出現し、NTの中止により改善がみられた1例を経験した。NT25mg,PRX30mgの最終服用24時間後に測定したNTの血漿濃度は120ng/mLであり、シミュレーション・カーブからは、有害事象が出現した日の早朝には血漿NT濃度が310ng/mL以上になっていたと推計された。PRXによるCYP2D6阻害や同酵素の飽和によりNTの代謝が阻害されたため、血漿NT濃度が上昇し、PRXとの相乗効果で錐体外路症状が惹起されたものと推察された。薬物併用時に有害事象が生じた場合には、therapeutic drug monitoringが薬物相互作用の検出に有用と考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J00990&link_issn=&doc_id=20080121080011&doc_link_id=%2Fdg3nigta%2F2007%2F012110%2F011%2F0589-0589%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2007%2F012110%2F011%2F0589-0589%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(株)星和書店  

これまでの臨床精神薬理学研究では、少数の遺伝子と臨床効果との関連解析から臨床効果予測に有用な遺伝子マーカーが同定されてきたが、臨床効果という表現型には複数の遺伝子およびそれらの間の相互作用、社会・環境的因子などさまざまな要因が影響しているため1つの遺伝子マーカーの同定では治療効果予測に十分なパワーを持たない。こうした背景とゲノム技術の発展により、包括的・網羅的な遺伝子解析から臨床効果を予測する薬理ゲノム学的アプローチへの関心が高まっている。しかし、薬理ゲノム研究によるオーダーメイド薬物治療実現には、遺伝子間の相互作用を仮定した解析方法の確立、ゲノム情報と臨床情報、社会・環境因子を統合したデータベース構築など多くの課題がある。またtheragnosticsの概念から、薬理遺伝学・薬理ゲノム研究とプロテオーム研究やメタボローム研究との連携の重要性が示唆されており、それらは今後の薬理遺伝学・薬理ゲノム研究に活用されるべきである。(著者抄録)

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

olanzapine(OLZ)の臨床効果および副作用とドパミンD2、D3受容体遺伝子多型との関連について検討した。外来通院中の統合失調症患者43例を対象とした。DRD2遺伝子Taq1多型とOLZの治療効果との間に関連が見出され、未治療患者に対するOLZの反応性予測因子として、A1遺伝子型が有用である可能性が示唆された。新規抗精神病薬が血中プロラクチン濃度、QT時間に及ぼす影響について検討した。外来通院、入院中の統合失調症患者89例を対象とした。risperidone内服群では、olanzapine群、perospirone群よりも平均血中プロラクチン濃度が有意に高く、olanzapine群では、1日用量が20mgより高い群では、用量が10mg未満の群、10mg以上20mg未満の群と比較して、平均血中プロラクチン濃度が有意に高かった。QT時間は薬剤間で差はみられなかった。

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記述言語：日本語   出版者・発行元：(株)星和書店  

精神科領域においては、以前より統合失調症患者やうつ病患者で心血管疾患による死亡率が一般人口に比べ高かった。また、少数ではあるが統合失調症患者でメタボリック・シンドロームの有病率の高さを示す報告がある。向精神薬がメタボリック・シンドロームの発症に与える影響が多数報告されているが、精神疾患そのものもメタボリック・シンドロームの発症に影響を与えていると考えられる。過去の研究から、精神疾患におけるHPA axisの調節障害、うつ病患者における交感神経系の活動性の増加、精神疾患とメタボリック・シンドロームの構成因子との間の遺伝学的共通性、統合失調症やうつ病における身体の活動性低下などが、単独あるいは複合してメタボリック・シンドロームを発症させることが示唆される。精神疾患患者の診療にあたっては、メタボリック・シンドロームの予防、発見、早期介入へのより一層の配慮が必要である。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)南山堂  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J00990&link_issn=&doc_id=20061219020012&doc_link_id=%2Fdg3nigta%2F2006%2F012010%2F012%2F0599-0600%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdg3nigta%2F2006%2F012010%2F012%2F0599-0600%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

記述言語：日本語   出版者・発行元：日本神経化学会  

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記述言語：日本語   出版者・発行元：日本神経化学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

抗精神病薬による性機能障害は比較的頻度が高く,服薬アドヒアランスや生活の質(QOL)を低下させる重大な有害事象であるにもかかわらず,臨床場面では十分な注意が払われていない.今回我々は,risperidone(RIS)2mg/日にて精神病症状は改善し病識も得られたが勃起障害のために服薬を拒否するようになり,olanzapine(OLZ)10mg/日に変更したところ勃起障害が消失し服薬アドヒアランスも保たれた,38歳男性の統合失調症の1例を経験した.他の非定型抗精神病薬と比較し,RISはドパミンD2およびα1アドレナリン受容体遮断作用が強く,高プロラクチン血症をきたしやすいために性機能障害を惹起しやすいと考えられている.RISによる性機能障害に対してはOLZやquetiapineへの変更が有効である可能性が示唆されており,今後の更なる症例の蓄積と大規模な臨床研究が期待される(著者抄録)

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記述言語：日本語   出版者・発行元：(株)医学書院  

進行性核上性麻痺(PSP)に対してミルナシプランの単剤投与(25mg/日)を行ったところ,意欲低下,姿勢反射障害,眼球運動障害などに改善がみられたPSPの1例(66歳男性)を報告した.投与開始4日後には姿勢反射障害や眼球運動障害が改善し,3週目からは意欲の向上もみられた.本症例はミルナシプラン単剤投与による効果がみられた点で意義があると考えられ,ミルナシプランはPSPの治療に有効である可能性が示唆された

DOI： 10.11477/mf.1405100253

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J00749&link_issn=&doc_id=20060417290011&doc_link_id=10.11477%2Fmf.1405100253&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1405100253&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：日本語   出版者・発行元：(株)星和書店  

うつ病の治療は抗うつ薬による薬物治療が主体をなしているが,抗うつ薬の選択や投与量については科学的根拠が十分に得られていないのが現状である.実際の臨床では,精神症状の改善や副作用を臨床的に評価することによって,薬物の用量の調整を行い,またその薬物を継続するか他剤に変更するかなどの判断を行っている.しかし,同じ薬剤で同じ投与量であっても血中濃度は個人間で非常に大きなばらつきがあるので,投与量のみによって適切な治療計画を立てることは困難であり,客観的な指標である薬物血中モニタリング(TDM)を利用して治療計画を立てることが望まれる.三環系抗うつ薬(TCA)においてはTDMに関する研究が蓄積されその有用性が確立されているが,近年第一選択薬となっている選択的セロトニン再取り組み阻害薬(SSRI)におけるTDMの意義は確立しておらず,臨床レベルで利用されるには至っていない(著者抄録)

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

新規抗精神病薬服用中の統合失調症患者において,体重増加,耐糖能異常,高prolactin血症などの副作用の経時的変化を検討し,悪性症候群(NMS)とドーパミンD2受容体(DRD2)遺伝子多型との関連について検討した.NMSの発症とDRD2遺伝子多型との間に関連は見出せなかった.しかし,olanzapineにより著しい体重増加をきたす症例では血中insulinおよびleptin濃度の顕著な上昇を認めることが示唆された.抗精神病薬による体重増加と治療前のBMIに相関がみられることも示唆された

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記述言語：日本語   出版者・発行元：(株)永井書店  

うつ病や統合失調症などの精神疾患の治療は,抗うつ薬や抗精神病薬といった向精神薬による薬物療法が主体をなしている.向精神薬の治療反応性や副作用発現には個人差があるが,それらの予測因子は同定されておらず,薬剤の選択基準および投与量についての科学的根拠は十分に得られていないのが現状である.この問題に対処するために,ゲノムレベルから薬物の反応性や副作用の発現を予測しようとする薬理遺伝学的研究(ファルマコジェネティクス)が現在さかんに行われている.本稿では,向精神薬の作用部位である各種受容体の遺伝子多型と向精神薬の効果,副作用の関係を調べたファルマコジェネティクスについて,当教室の検討結果を提示しながら,現在知られている代表的な知見を概説する.また,多くの向精神薬の代謝に関与するチトクロームP450を対象としたファルマコジェネティクスについても述べる(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(株)南山堂  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

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記述言語：日本語   出版者・発行元：(公財)先進医薬研究振興財団  

5-HT2A,5-HT3受容体及びCYP2D6遺伝子多型がfluvoxamine(FLV)による消化器系副作用出現に与える影響を検討した.うつ病患者100例を対象とした.5-HT2A受容体A-1438G多型のGアレルの数は消化器系副作用出現に有意な影響を与え,G/G遺伝子型はA/A型に比べて2.926倍副作用出現頻度が高かった.CYP2D6のpoor metabolizer(PM)はextensive metabolizer(EM)に比べて,副作用出現頻度が有意に高かった.CYP2D6表現型とA-1438G遺伝子型とを組み合わせて分析し,PMでA/GまたはG/G遺伝子型を持つ個体の副作用出現リスクは,EMでA/A遺伝子型を持つ個体に比べてそれぞれ4.147,4.242倍であった

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記述言語：日本語   出版者・発行元：(株)ライフメディコム  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)アークメディア  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：(株)星和書店  

33歳男.統合失調症に対し,薬物療法が続けられたが,家庭での暴力が徐々に増してきた.退院した頃から徐々に飲水量が多くなった.嘔吐,発熱,意識障害が出現した.CPKとLDH高値,横紋筋融解の所見と筋強剛を認めたため,悪性症候群と診断した.輸液とdantroleneにより症状は軽快し,入院後33日目に退院した.外来治療が継続されたが,日常的に病的多飲水が続いていた.頻回に嘔吐し,けいれん発作を起こし,緊急入院した.入院後3日目には,意識障害は改善し,入院後4日目には意識清明となった.入院後23日目に,急に我慢できない程のイライラ感を訴えるようになったため,olanzapineを開始した.イライラ感は速やかに消失した.悪性症候群の再燃や,病的多飲水を認めなかったので,入院後60日目に退院した

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記述言語：日本語   出版者・発行元：(有)医学の世界社  

子宮内膜症発症に関与する疾患感受性遺伝子を同定し,発症メカニズムの解明,発症予防,新たな治療法の開発を目的として,家系集積の必要がなくゲノムワイドでの候補遺伝子限定が可能な3万マイクロサテライトマーカーを用いた患者・対照群相関解析,正常子宮内膜と子宮内膜症組織を対象としたDNA chipでの12000遺伝子の発現解析を同時に開始した.全染色体にわたり23277マイクロサテライトマーカーの設定が終了し,一次スクリーニングでは1434マーカーが陽性を示し,二次スクリーニングを行った結果,349マーカーが更に陽性を示した.12000遺伝子の発現解析で,294遺伝子に発現量の変化が認められた.11遺伝子が二次スクリーニング陽性マーカーの近傍100kb以内に位置し,疾患感受性遺伝子である可能性が示唆された

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

症例1は34歳.1妊1産で,妊娠25週1日に切迫早産と羊水過少症のため,著者ら施設へ母体搬送となった.塩酸リトドリン投与を行ったが,極端な羊水過少の持続がみられ,ポッター症候群を疑った.妊娠33週0日,混濁した羊水漏出を認め,児が横位であったため帝王切開を行った.症例2は29歳の初産婦で,近医にてICSIにより妊娠が成立し,妊娠23週6日に前期破水,切迫早産を認め,著者ら施設へ母体搬送となった.妊娠26週〜35週の経過で胎児発育遅延(-3.2SD)を認めたが,極端な羊水過少のため胎児下肢は正確に描出されず,妊娠37週0日に帝王切開を行った.いずれの症例も新生児は,単一臍帯動脈の人魚体症候群で,症例1はアプガー1/1,体重1646g,身長36cm,症例2はアプガー0/1,体重1788g,身長35cmであった.いずれの新生児も性別不明で,それぞれ4時間後,3時間後に死亡した.レントゲン検査では,仙骨・腓骨の欠損,両足の癒合,両腎の無形成が示された

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：日本語   出版者・発行元：(公社)日本産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟医学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：日本産科婦人科学会-東北連合地方部会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：日本産科婦人科学会-東北連合地方部会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

鎖肛の手術既往のある25歳の初産婦を経験した.入院時の会陰の所見と直腸診所見にて分娩様式は帝王切開に決定していたが,切迫早産徴候のコントロール不能となり,34週2日に緊急帝王切開にて生児を得た.手術時の所見より,単頸双角子宮と判明した.母体の術後経過は順調で,術後8日目に退院した.児は低出生体重児で,一時NICU管理後に退院し,その後の発育は順調である

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：(株)診断と治療社  

再生不良性貧血合併妊娠・分娩のポイントとして,妊娠時には輸血を最小限にして,分娩時には血小板数が5万/mm3以上になるように濃厚血小板を輸血すること,出血傾向と感染症の厳重なモニターが重要であること,新生児血液所見は正常であり,産科的適応がない限り経腟分娩が可能であることが示唆された

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記述言語：日本語   出版者・発行元：日本産科婦人科学会-東北連合地方部会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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記述言語：日本語   出版者・発行元：新潟産科婦人科学会  

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