Naotaka Shinfuku - Profile on Academia.edu (original) (raw)
Papers by Naotaka Shinfuku
International Journal of Molecular Medicine, Aug 1, 2004
Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpr... more Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpressed in pancreatic islets. The present study examines development of four islet hormones in PPTG mice at embryonic days (ED) 15, 17, and 19, and in adult animals. Adult PPTG mice showed massive aggregation of PP-positive cells and glucagonpositive cells seen at the central area of the islets. Confocal laser microscopic study showed that three islet hormones (insulin, glucagon and PP) were completely overlapped in islets of PPTG mice. Overlapping of somatostatin/glucagon and somatostatin/PP were also increased at the peripheral area of the islets in adult PPTG mice compared to wild-type mice. In prenatal development of pancreatic islets of PPTG mice, somatostatin/glucagon overlapping cells appeared at ED 15, two days earlier than in wild-type mice. Differentiation of these somatostatin/glucagon double-positive cells into single-positive cells was disturbed in the PPTG mice during perinatal to postnatal periods. Differentiation of glucagon/ insulin-double positive cells into single-positive cells was disturbed remarkably in postnatal development of the islets of PPTG mice. The present results suggest that early and overexpression of PP may engender the early appearance of somatostatin producing cells; however, that may disturb differentiation of multihormonal immature endocrine cells into single hormonal mature endocrine cells.
International Journal of Molecular Medicine, Jun 1, 2005
Urocortin, a recently identified member of the corticotropin-releasing factor (CRF) family, is im... more Urocortin, a recently identified member of the corticotropin-releasing factor (CRF) family, is implicated in the central control of appetite and energy metabolism. We previously reported that peripherally administered urocortin inhibits gastric emptying in conscious mice. In this study, we investigated the effect of intracerebroventricularly administered urocortin on gastric emptying, food intake and body weight in mice. Urocortin decreased food intake and body weight gain more potently than CRF. It significantly decreased gastric emptying of a solid meal; an effect that was inhibited by simultaneous administration of a-helical CRF 9 . 4 ,, a CRF antagonist. These results suggest that the potent anorectic properties of urocortin may be partly due to the anti-gastroprokinetic activity of the peptide.
Peptide YY3-36 and pancreatic polypeptide suppress food intake
Journal of Gastroenterology and Hepatology, Jul 28, 2006
To the Editor , Here, we show that peptide YY (PYY) 3–36 and pancreatic polypeptide (PP) suppress... more To the Editor , Here, we show that peptide YY (PYY) 3–36 and pancreatic polypeptide (PP) suppress food intake in both lean mice and ob/ob obese mice. Pancreatic polypeptide and PYY are 36 amino acid peptides that belong to a family of peptides including neuropeptide Y (NPY). Since the discovery of leptin and ghrelin, much progress has been made in the study of controlling energy homeostasis. Until now, various peptides, including NPY, ghrelin, agoutirelated protein (AGRP), orexin, melanin-concentrating hormone (MCH), leptin, α -melanocyte-stimulating hormone (MSH), cocaineand amphetamine-regulated transcript (CART), cholecystokinin (CCK), corticotropin-releasing factor (CRF) and urocortin, have been shown to be involved in the regulation of food intake. Tschop et al . reported that gut hormone PYY3-36 does not suppress food intake in rodents and they cannot replicate the anorexigenic effects of PYY3-36 reported by Batterham et al . 1–3
Gut, 2005
Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogu... more Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance. Methods: The authors measured food intake, gastric emptying, c-Fos expression in the hypothalamus, and gene expression of hypothalamic neuropeptides in mice after administration of desacyl ghrelin. To explore the effects of long term overexpression of desacyl ghrelin, transgenic mice that overexpressed desacyl ghrelin were created. Results: Administration of desacyl ghrelin decreased food intake and gastric emptying rate through an action on the paraventricular nucleus and the arcuate nucleus in the hypothalamus. Gene expression of anorexigenic cocaine and amphetamine regulated transcript and urocortin in the hypothalamus was increased by desacyl ghrelin. Desacyl ghrelin overexpressing mice exhibited a decrease in body weight, food intake, and fat pad mass weight accompanied by moderately decreased linear growth. Gastric emptying was also decreased in desacyl ghrelin overexpressing mice. Conclusions: These findings indicate that in contrast to acylated ghrelin, desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying. The effect is mediated via the hypothalamus. Although derived from the same precursor, the inverse effects of these two peptides suggest that the stomach might be involved as an endocrine organ in the regulation of the energy balance.
Melanin-concentrating hormone enhances sucrose intake
International Journal of Molecular Medicine, Jun 1, 2005
Melanin-concentrating hormone (MCH) is known to be an important regulator for feeding and energy ... more Melanin-concentrating hormone (MCH) is known to be an important regulator for feeding and energy balance. MCH was recently reported to stimulate water intake independent of food intake. The purpose of the present study is to examine the dipsogenic response of MCH with special emphasis on sweetened beverages, the preference for which is well documented in diabetic animals. Our results showed that intracerebroventricular injection of MCH acutely increased food as well as water intake. Human (h)MCH and salmon (s)MCH increased water intake independent of food intake, which was not suppressed by angiotensin antagonists. hMCH and sMCH significantly increased both sucrose solution and food intake; on the other hand, agouti-related protein (AgRP) stimulated food but not sucrose intake when provided simultaneously. MCH-treated rats significantly increased the ingestion of sucrose and glucose solution, but not of saccharin, indicating that MCH-induced dipsogenic response is more related to caloric content than sweet taste per se. Significant correlation was observed between the sucrose intake and the mRNA expression of MCH and MCHR1 in normal rats. These results indicate that MCH may be an important regulator of sugar intake in normal as well as in obese diabetic animals.
![Research paper thumbnail of [The mental health of school children after the Great Hanshin-Awaji Earthquake: I. Epidemiological study and risk factors for mental distress]](https://attachments.academia-assets.com/123172353/thumbnails/1.jpg)
](Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 2000
We conducted surveys to study the magnitude and nature of psychological consequences of school ch... more We conducted surveys to study the magnitude and nature of psychological consequences of school children affected by the Great Hanshin Awaji Earthquake, which occurred in Kobe on January 17th, 1995. It measured 7.2 in magnitude, killed more than 6000 people and destroyed at least 170,000 buildings and houses. The investigations were carried out 4 months following of the disaster. About 9000 school children in the 3rd grade, the 5th grade, the 8th grade living in the disaster areas. About 2000 children living in distant areas were also surveyed as control subjects. The questionnaire was in a self-descriptive format and consisted of 10 items regarding situation and behavior when the earthquake occurred and 22 items about mental health condition. The responses were rated from 1 to 4 depending on the frequency of the symptoms, and statistically analyzed. By factor analysis, three factors were elicited. Factor 1 was interpreted as being related to fear and anxiety, factor 2 as related to ...
International Journal of Molecular Medicine, 2004
Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpr... more Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpressed in pancreatic islets. The present study examines development of four islet hormones in PPTG mice at embryonic days (ED) 15, 17, and 19, and in adult animals. Adult PPTG mice showed massive aggregation of PP-positive cells and glucagonpositive cells seen at the central area of the islets. Confocal laser microscopic study showed that three islet hormones (insulin, glucagon and PP) were completely overlapped in islets of PPTG mice. Overlapping of somatostatin/glucagon and somatostatin/PP were also increased at the peripheral area of the islets in adult PPTG mice compared to wild-type mice. In prenatal development of pancreatic islets of PPTG mice, somatostatin/glucagon overlapping cells appeared at ED 15, two days earlier than in wild-type mice. Differentiation of these somatostatin/glucagon double-positive cells into single-positive cells was disturbed in the PPTG mice during perinatal to postnatal periods. Differentiation of glucagon/ insulin-double positive cells into single-positive cells was disturbed remarkably in postnatal development of the islets of PPTG mice. The present results suggest that early and overexpression of PP may engender the early appearance of somatostatin producing cells; however, that may disturb differentiation of multihormonal immature endocrine cells into single hormonal mature endocrine cells.
European Psychiatry, 2016
IntroductionUnder the Portuguese law, criminal offenders that are designated as non-criminal resp... more IntroductionUnder the Portuguese law, criminal offenders that are designated as non-criminal responsible – “inimputáveis”, similar those in the United States of America found “not guilty by reason of insanity”, are forced to be committed to inpatient forensic units either in psychiatric hospitals or prison hospitals for mandatory security measures.Objectives/aimsTo evaluate if patients committed in a regional forensic inpatient unit (RFIU) who had a psychiatric history preceding the crime, were under long acting injectable antipsychotic (LAIA) in during the period of the crime.MethodsDuring September/October 2015, patients committed to the RFIU in Centro Hospitalar Psiquiátrico de Lisboa were characterized using medical and court records regarding clinical and demographic variables. The type of crime and previous number of criminal acts were also accounted for.ResultsWe included 33 patients in the study. During time of the crime, 25 patients (75.8%) had history of previous psychiatr...
Psychiatry Investigation, Jun 25, 2019
first-degree relatives, and other factors. Among 362 patients diagnosed with BD, based on the Dia... more first-degree relatives, and other factors. Among 362 patients diagnosed with BD, based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, 4 patients with prior suicide attempt were characterized by polarity at onset, increased number of psychiatric hospitalization, psychiatric comorbidity, and treatment with lithium and polypharmacy (4 or more psychotropic drugs) compared to those without prior suicide attempts. 5 Moreover, the actigraphic findings revealed that the sleep and circadian rhythms of morning preference, vigorous circadian type, and earlier start of daily activity were potential trait differences in BD patients with suicide attempts from those without such attempts. Similar to the studies based on other ethnicities, this study aimed to investigate clinical correlations of suicide attempts in Asian patients
Nutrition Journal, Feb 9, 2005
We have previously shown that irregular lifestyle of young Japanese female students are significa... more We have previously shown that irregular lifestyle of young Japanese female students are significantly related to their desire to be thinner. In the present study, we examined the nutritional knowledge and food habits of Chinese university students and compared them with those of other Asian populations. Methods: A self-reported questionnaire was administered to 540 students, ranging in age from 19-24 years. Medical students from Beijing University (135 men and 150 women) in Northern China and Kunming Medical College in southern China (95 men and 160 women) participated in this study. The parametric variables were analyzed using the Student's t-test. Chi-square analyses were conducted for non-parametric variables Results: Our results showed that 80.5% of students had a normal BMI and 16.6 % of students were underweight with the prevalence of BMI>30 obesity being very low in this study sample. Young Chinese female students had a greater desire to be thinner (62.0%) than males (47.4%). Habits involving regular eating patterns and vegetable intake were reported and represent practices that ought to be encouraged. The university and college arenas represent the final opportunity for the health and nutritional education of a large number of students from the educator's perspective. Our findings suggest the need for strategies designed to improve competence in the area of nutrition.
Dosing of Mood Stabilizers for Bipolar Disorder Patients in the Research on Asian Psychotropic Prescription Patterns Consortium Study
Journal of Clinical Psychopharmacology
Abstract Background Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (B... more Abstract Background Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs. Methods We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in the Research on Asian Psychotropic Prescription Patterns Consortium. Mood stabilizer doses were converted to lithium carbonate equivalents (Li-eq milligrams per day). We compared relatively high (>900 Li-eq mg/day) versus lower MS doses by bivariate comparisons, followed by multivariable linear regression to identify factors associated with higher MS doses. Results Among 1647 participants, MS dose averaged 584 (confidence interval, 565–603 Li-eq mg/d). Preliminarily, the 13.1% of the subjects given greater than 900 mg/d versus those given lower doses were younger, male, currently hospitalized, not currently depressed, and reported lifetime suicidal ideation; they also received relatively high doses of antipsychotics, received electroconvulsive treatment within the previous 12 months, and had greater ratings of tremors and sedation. By linear regression modeling, the mean proportion given high doses of MS was associated significantly and independently with higher doses of antipsychotics, younger age, male sex, hospitalized, more years of illness, country, higher body mass index, recent electroconvulsive treatment, and being in illness remission. Conclusions Relatively high doses of MSs for BD are prevalent, but vary markedly among Asian countries, and are particularly likely among young males, ill for many years, and given high doses of antipsychotics or ECT. These characteristics allow better identification of patient profiles that can guide treatment of BD patients.
Clozapine Use for Bipolar Disorder
Journal of Clinical Psychopharmacology
The factor structure of extrapyramidal symptoms evaluated using the Drug‐Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP‐4 study
Human Psychopharmacology: Clinical and Experimental
IntroductionDrug‐induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychi... more IntroductionDrug‐induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug‐induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug‐Induced Extrapyramidal Symptoms Scale (DIEPSS).MethodsThe participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP‐4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis.ResultsThe factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia).ConclusionThe results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute pa...
The Track of my Life and the Explanatory Notes on my Works
Urban Mental Health in the Twenty-First Century
Advances in Psychiatry, 2018
Mental Health Care in 11 Major Cities Over Two Decades
This chapter investigates how mental health services have changed over the past two decades in a ... more This chapter investigates how mental health services have changed over the past two decades in a selection of 11 major cities from four different continents. Overall, deinstitutionalization has moved patient care away from hospitals and into community settings where mental health centers are now developing outpatient services. The cities presented are Amsterdam (the Netherlands), Baltimore (the United States), Bangalore (India), Copenhagen (Denmark), Kobe (Japan), London (United Kingdom), Porto Alegre (Brazil), Sydney (Australia), Madison (the United States), Tehran (Iran), and Verona (Italy). These cities have been selected to represent a global perspective including different continents, cultures, D. Goldberg (*) Institute of Psychiatry, King’s College London, London, UK G. Thornicroft Institute of Psychiatry Psychology and Neuroscience of King’s College, London, UK M. Abbasinejad Department for Mental Health and Substance Abuse, Roozbeh Hospital, Tehran, University of Medical Sciences, Tehran, Iran F. Amaddeo Department of Neurosciences, Biomedicine andMovement Sciences, University of Verona, Verona, Italy e-mail: francesco.amaddeo@univr.it G. Andrews CRUfAD, UNSW at St Vincent’s Hospital, Darlinghurst, NSW, Australia e-mail: gavina@unsw.edu.au # Springer Science+Business Media Singapore 2017 N. Okkels et al. (eds.), Mental Health and Illness in the City, Mental Health and Illness Worldwide, https://doi.org/10.1007/978-981-10-2327-9_19 223 and religions. This chapter reports of several promising community care initiatives and evidence that the era of institutionalization may be ending.
Nordic Journal of Psychiatry, 2020
Background: Network analysis provides a new viewpoint that explicates intertwined and interrelate... more Background: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology. Aims: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. Methods: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. Results: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clustersextrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. Conclusions: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.
The Kaohsiung journal of medical sciences, 2018
Our study aimed to assess the psychometric validity of the conceptual disorganization item and ot... more Our study aimed to assess the psychometric validity of the conceptual disorganization item and other items of the Brief Psychiatric Rating Scale (BPRS) for detecting disorganized speech in patients with schizophrenia. We included 357 schizophrenia patients with disorganized speech and 1082 without disorganized speech from the survey centers in India, Indonesia, Japan, Malaysia, and Taiwan, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. After adjusting the effects of confounding variables, a binary logistic regression model was fitted to identify BPRS items independently associated with disorganized speech. Receiver operating characteristic (ROC) curves were used to identify optimum cut-off scores and their sensitivities and specificities for detecting disorganized speech. After adjusting the effects of confounding variables, the fitted binary logistic regression model indicated that conceptual disorganization (P < 0.0001), unco...
High Dose Antipsychotic Use in Schizophrenia: Findings of the REAP (Research on East Asia Psychotropic Prescriptions) Study
Pharmacopsychiatry, 2004
High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equ... more High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the management of patients with schizophrenia are not uncommon, but most reports are from western countries. Recent functional neuroimaging studies have found that the previous notion concerning the use of antipsychotic medication, especially in high doses, was unsupported and untenable. This international study examined the use of high dose antipsychotic medication and its clinical correlates in schizophrenia patients within six East Asian countries/territories. Within the study group (n = 2399), 430 patients (17.9%) were prescribed high dose antipsychotics. Antipsychotic use varied significantly between countries, with Japan, Korea, and Singapore using higher doses than the other countries. High dose antipsychotic use was associated with younger age in Japan (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001), longer duration of admission (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001), duration of illness (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001, particularly in Japan and Korea), and aggression (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.05, particularly in Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse effects (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.05, particularly in China). Country, younger age, the presence of delusions and disorganized speech, polypharmacy, and receiving depot medication but not atypical antipsychotic drugs were important predictors of high antipsychotic use. This survey revealed that high antipsychotic dosing is not an uncommon practice in East Asia. It behooves the prescribing clinicians to constantly reevaluate the rationale for such a practice.
International Clinical Psychopharmacology, 2001
Ensuring safety of pharmaceuticals is one of the most important objectives of the Pharmaceutical ... more Ensuring safety of pharmaceuticals is one of the most important objectives of the Pharmaceutical Affairs Law. Safety information obtained by the approval is limited because size of the subjects in clinical trials is small and factors on subjects such as concomitant use of other drugs are controlled. Therefore, safety of pharmaceuticals is ensured through information obtained during long postmarketing periods. Under the Law, the manufacturers shall report to the Ministry once they know a certain category of safety information. Also, the Ministry has a system by which medical professionals can directly report safety information. Ž . In PMS Post-Marketing Surveillance , the collection of safety information in early stages of the sale of new drug has an extremely important meaning. During a short period of time after the launch, the number of patients prescribed will dramatically increase and the drug is administered to diverse patients with different backgrounds. This is the period when important adverse reactions are discovered that have not been detected during the development stage. MoHW considers introducing ''Early Post Marketing Phase Vigilance'' in order to collect information on serious adverse reactions thoroughly that may come out just after the launch and to take necessary measures as soon as possible.
International Journal of Molecular Medicine, Aug 1, 2004
Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpr... more Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpressed in pancreatic islets. The present study examines development of four islet hormones in PPTG mice at embryonic days (ED) 15, 17, and 19, and in adult animals. Adult PPTG mice showed massive aggregation of PP-positive cells and glucagonpositive cells seen at the central area of the islets. Confocal laser microscopic study showed that three islet hormones (insulin, glucagon and PP) were completely overlapped in islets of PPTG mice. Overlapping of somatostatin/glucagon and somatostatin/PP were also increased at the peripheral area of the islets in adult PPTG mice compared to wild-type mice. In prenatal development of pancreatic islets of PPTG mice, somatostatin/glucagon overlapping cells appeared at ED 15, two days earlier than in wild-type mice. Differentiation of these somatostatin/glucagon double-positive cells into single-positive cells was disturbed in the PPTG mice during perinatal to postnatal periods. Differentiation of glucagon/ insulin-double positive cells into single-positive cells was disturbed remarkably in postnatal development of the islets of PPTG mice. The present results suggest that early and overexpression of PP may engender the early appearance of somatostatin producing cells; however, that may disturb differentiation of multihormonal immature endocrine cells into single hormonal mature endocrine cells.
International Journal of Molecular Medicine, Jun 1, 2005
Urocortin, a recently identified member of the corticotropin-releasing factor (CRF) family, is im... more Urocortin, a recently identified member of the corticotropin-releasing factor (CRF) family, is implicated in the central control of appetite and energy metabolism. We previously reported that peripherally administered urocortin inhibits gastric emptying in conscious mice. In this study, we investigated the effect of intracerebroventricularly administered urocortin on gastric emptying, food intake and body weight in mice. Urocortin decreased food intake and body weight gain more potently than CRF. It significantly decreased gastric emptying of a solid meal; an effect that was inhibited by simultaneous administration of a-helical CRF 9 . 4 ,, a CRF antagonist. These results suggest that the potent anorectic properties of urocortin may be partly due to the anti-gastroprokinetic activity of the peptide.
Peptide YY3-36 and pancreatic polypeptide suppress food intake
Journal of Gastroenterology and Hepatology, Jul 28, 2006
To the Editor , Here, we show that peptide YY (PYY) 3–36 and pancreatic polypeptide (PP) suppress... more To the Editor , Here, we show that peptide YY (PYY) 3–36 and pancreatic polypeptide (PP) suppress food intake in both lean mice and ob/ob obese mice. Pancreatic polypeptide and PYY are 36 amino acid peptides that belong to a family of peptides including neuropeptide Y (NPY). Since the discovery of leptin and ghrelin, much progress has been made in the study of controlling energy homeostasis. Until now, various peptides, including NPY, ghrelin, agoutirelated protein (AGRP), orexin, melanin-concentrating hormone (MCH), leptin, α -melanocyte-stimulating hormone (MSH), cocaineand amphetamine-regulated transcript (CART), cholecystokinin (CCK), corticotropin-releasing factor (CRF) and urocortin, have been shown to be involved in the regulation of food intake. Tschop et al . reported that gut hormone PYY3-36 does not suppress food intake in rodents and they cannot replicate the anorexigenic effects of PYY3-36 reported by Batterham et al . 1–3
Gut, 2005
Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogu... more Background/Aims: The gastric peptide ghrelin, an endogenous ligand for growth-hormone secretagogue receptor, has two major molecular forms: acylated ghrelin and desacyl ghrelin. Acylated ghrelin induces a positive energy balance, while desacyl ghrelin has been reported to be devoid of any endocrine activities. The authors examined the effects of desacyl ghrelin on energy balance. Methods: The authors measured food intake, gastric emptying, c-Fos expression in the hypothalamus, and gene expression of hypothalamic neuropeptides in mice after administration of desacyl ghrelin. To explore the effects of long term overexpression of desacyl ghrelin, transgenic mice that overexpressed desacyl ghrelin were created. Results: Administration of desacyl ghrelin decreased food intake and gastric emptying rate through an action on the paraventricular nucleus and the arcuate nucleus in the hypothalamus. Gene expression of anorexigenic cocaine and amphetamine regulated transcript and urocortin in the hypothalamus was increased by desacyl ghrelin. Desacyl ghrelin overexpressing mice exhibited a decrease in body weight, food intake, and fat pad mass weight accompanied by moderately decreased linear growth. Gastric emptying was also decreased in desacyl ghrelin overexpressing mice. Conclusions: These findings indicate that in contrast to acylated ghrelin, desacyl ghrelin induces a negative energy balance by decreasing food intake and delaying gastric emptying. The effect is mediated via the hypothalamus. Although derived from the same precursor, the inverse effects of these two peptides suggest that the stomach might be involved as an endocrine organ in the regulation of the energy balance.
Melanin-concentrating hormone enhances sucrose intake
International Journal of Molecular Medicine, Jun 1, 2005
Melanin-concentrating hormone (MCH) is known to be an important regulator for feeding and energy ... more Melanin-concentrating hormone (MCH) is known to be an important regulator for feeding and energy balance. MCH was recently reported to stimulate water intake independent of food intake. The purpose of the present study is to examine the dipsogenic response of MCH with special emphasis on sweetened beverages, the preference for which is well documented in diabetic animals. Our results showed that intracerebroventricular injection of MCH acutely increased food as well as water intake. Human (h)MCH and salmon (s)MCH increased water intake independent of food intake, which was not suppressed by angiotensin antagonists. hMCH and sMCH significantly increased both sucrose solution and food intake; on the other hand, agouti-related protein (AgRP) stimulated food but not sucrose intake when provided simultaneously. MCH-treated rats significantly increased the ingestion of sucrose and glucose solution, but not of saccharin, indicating that MCH-induced dipsogenic response is more related to caloric content than sweet taste per se. Significant correlation was observed between the sucrose intake and the mRNA expression of MCH and MCHR1 in normal rats. These results indicate that MCH may be an important regulator of sugar intake in normal as well as in obese diabetic animals.
Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 2000
We conducted surveys to study the magnitude and nature of psychological consequences of school ch... more We conducted surveys to study the magnitude and nature of psychological consequences of school children affected by the Great Hanshin Awaji Earthquake, which occurred in Kobe on January 17th, 1995. It measured 7.2 in magnitude, killed more than 6000 people and destroyed at least 170,000 buildings and houses. The investigations were carried out 4 months following of the disaster. About 9000 school children in the 3rd grade, the 5th grade, the 8th grade living in the disaster areas. About 2000 children living in distant areas were also surveyed as control subjects. The questionnaire was in a self-descriptive format and consisted of 10 items regarding situation and behavior when the earthquake occurred and 22 items about mental health condition. The responses were rated from 1 to 4 depending on the frequency of the symptoms, and statistically analyzed. By factor analysis, three factors were elicited. Factor 1 was interpreted as being related to fear and anxiety, factor 2 as related to ...
International Journal of Molecular Medicine, 2004
Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpr... more Recently we produced pancreatic polypeptide transgenic (PPTG) mice and found that PP was overexpressed in pancreatic islets. The present study examines development of four islet hormones in PPTG mice at embryonic days (ED) 15, 17, and 19, and in adult animals. Adult PPTG mice showed massive aggregation of PP-positive cells and glucagonpositive cells seen at the central area of the islets. Confocal laser microscopic study showed that three islet hormones (insulin, glucagon and PP) were completely overlapped in islets of PPTG mice. Overlapping of somatostatin/glucagon and somatostatin/PP were also increased at the peripheral area of the islets in adult PPTG mice compared to wild-type mice. In prenatal development of pancreatic islets of PPTG mice, somatostatin/glucagon overlapping cells appeared at ED 15, two days earlier than in wild-type mice. Differentiation of these somatostatin/glucagon double-positive cells into single-positive cells was disturbed in the PPTG mice during perinatal to postnatal periods. Differentiation of glucagon/ insulin-double positive cells into single-positive cells was disturbed remarkably in postnatal development of the islets of PPTG mice. The present results suggest that early and overexpression of PP may engender the early appearance of somatostatin producing cells; however, that may disturb differentiation of multihormonal immature endocrine cells into single hormonal mature endocrine cells.
European Psychiatry, 2016
IntroductionUnder the Portuguese law, criminal offenders that are designated as non-criminal resp... more IntroductionUnder the Portuguese law, criminal offenders that are designated as non-criminal responsible – “inimputáveis”, similar those in the United States of America found “not guilty by reason of insanity”, are forced to be committed to inpatient forensic units either in psychiatric hospitals or prison hospitals for mandatory security measures.Objectives/aimsTo evaluate if patients committed in a regional forensic inpatient unit (RFIU) who had a psychiatric history preceding the crime, were under long acting injectable antipsychotic (LAIA) in during the period of the crime.MethodsDuring September/October 2015, patients committed to the RFIU in Centro Hospitalar Psiquiátrico de Lisboa were characterized using medical and court records regarding clinical and demographic variables. The type of crime and previous number of criminal acts were also accounted for.ResultsWe included 33 patients in the study. During time of the crime, 25 patients (75.8%) had history of previous psychiatr...
Psychiatry Investigation, Jun 25, 2019
first-degree relatives, and other factors. Among 362 patients diagnosed with BD, based on the Dia... more first-degree relatives, and other factors. Among 362 patients diagnosed with BD, based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, 4 patients with prior suicide attempt were characterized by polarity at onset, increased number of psychiatric hospitalization, psychiatric comorbidity, and treatment with lithium and polypharmacy (4 or more psychotropic drugs) compared to those without prior suicide attempts. 5 Moreover, the actigraphic findings revealed that the sleep and circadian rhythms of morning preference, vigorous circadian type, and earlier start of daily activity were potential trait differences in BD patients with suicide attempts from those without such attempts. Similar to the studies based on other ethnicities, this study aimed to investigate clinical correlations of suicide attempts in Asian patients
Nutrition Journal, Feb 9, 2005
We have previously shown that irregular lifestyle of young Japanese female students are significa... more We have previously shown that irregular lifestyle of young Japanese female students are significantly related to their desire to be thinner. In the present study, we examined the nutritional knowledge and food habits of Chinese university students and compared them with those of other Asian populations. Methods: A self-reported questionnaire was administered to 540 students, ranging in age from 19-24 years. Medical students from Beijing University (135 men and 150 women) in Northern China and Kunming Medical College in southern China (95 men and 160 women) participated in this study. The parametric variables were analyzed using the Student's t-test. Chi-square analyses were conducted for non-parametric variables Results: Our results showed that 80.5% of students had a normal BMI and 16.6 % of students were underweight with the prevalence of BMI>30 obesity being very low in this study sample. Young Chinese female students had a greater desire to be thinner (62.0%) than males (47.4%). Habits involving regular eating patterns and vegetable intake were reported and represent practices that ought to be encouraged. The university and college arenas represent the final opportunity for the health and nutritional education of a large number of students from the educator's perspective. Our findings suggest the need for strategies designed to improve competence in the area of nutrition.
Dosing of Mood Stabilizers for Bipolar Disorder Patients in the Research on Asian Psychotropic Prescription Patterns Consortium Study
Journal of Clinical Psychopharmacology
Abstract Background Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (B... more Abstract Background Because use and dosing of mood stabilizers (MSs) to treat bipolar disorder (BD) patients in Asia are not well documented, we examined prevalence and clinical correlates of treatment of Asian BD patients with relatively high doses of MSs. Methods We conducted a pharmacoepidemiological survey across 13 Asian countries and territory in the Research on Asian Psychotropic Prescription Patterns Consortium. Mood stabilizer doses were converted to lithium carbonate equivalents (Li-eq milligrams per day). We compared relatively high (>900 Li-eq mg/day) versus lower MS doses by bivariate comparisons, followed by multivariable linear regression to identify factors associated with higher MS doses. Results Among 1647 participants, MS dose averaged 584 (confidence interval, 565–603 Li-eq mg/d). Preliminarily, the 13.1% of the subjects given greater than 900 mg/d versus those given lower doses were younger, male, currently hospitalized, not currently depressed, and reported lifetime suicidal ideation; they also received relatively high doses of antipsychotics, received electroconvulsive treatment within the previous 12 months, and had greater ratings of tremors and sedation. By linear regression modeling, the mean proportion given high doses of MS was associated significantly and independently with higher doses of antipsychotics, younger age, male sex, hospitalized, more years of illness, country, higher body mass index, recent electroconvulsive treatment, and being in illness remission. Conclusions Relatively high doses of MSs for BD are prevalent, but vary markedly among Asian countries, and are particularly likely among young males, ill for many years, and given high doses of antipsychotics or ECT. These characteristics allow better identification of patient profiles that can guide treatment of BD patients.
Clozapine Use for Bipolar Disorder
Journal of Clinical Psychopharmacology
The factor structure of extrapyramidal symptoms evaluated using the Drug‐Induced Extrapyramidal Symptoms Scale in patients with schizophrenia: Results from the 2016 REAP AP‐4 study
Human Psychopharmacology: Clinical and Experimental
IntroductionDrug‐induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychi... more IntroductionDrug‐induced extrapyramidal syndrome (EPS) remains a major problem in clinical psychiatry. This study aimed to examine the factor structure of drug‐induced extrapyramidal symptoms observed in patients with schizophrenia and assessed using the Drug‐Induced Extrapyramidal Symptoms Scale (DIEPSS).MethodsThe participants were 1478 patients with a diagnosis of schizophrenia whose EPS was assessed using the DIEPSS in India, Indonesia, Japan, Malaysia, and Taiwan in the 2016 REAP AP‐4 study. The records of the participants were randomly divided into two subgroups: the first for exploratory factor analysis of the eight DIEPSS items, and the second for confirmatory factor analysis.ResultsThe factor analysis identified three factors: F1 (gait and bradykinesia), F2 (muscle rigidity and tremor), and F3 (sialorrhea, akathisia, dystonia, and dyskinesia).ConclusionThe results suggest that the eight individual items of the DIEPSS could be composed of three different mechanisms: acute pa...
The Track of my Life and the Explanatory Notes on my Works
Urban Mental Health in the Twenty-First Century
Advances in Psychiatry, 2018
Mental Health Care in 11 Major Cities Over Two Decades
This chapter investigates how mental health services have changed over the past two decades in a ... more This chapter investigates how mental health services have changed over the past two decades in a selection of 11 major cities from four different continents. Overall, deinstitutionalization has moved patient care away from hospitals and into community settings where mental health centers are now developing outpatient services. The cities presented are Amsterdam (the Netherlands), Baltimore (the United States), Bangalore (India), Copenhagen (Denmark), Kobe (Japan), London (United Kingdom), Porto Alegre (Brazil), Sydney (Australia), Madison (the United States), Tehran (Iran), and Verona (Italy). These cities have been selected to represent a global perspective including different continents, cultures, D. Goldberg (*) Institute of Psychiatry, King’s College London, London, UK G. Thornicroft Institute of Psychiatry Psychology and Neuroscience of King’s College, London, UK M. Abbasinejad Department for Mental Health and Substance Abuse, Roozbeh Hospital, Tehran, University of Medical Sciences, Tehran, Iran F. Amaddeo Department of Neurosciences, Biomedicine andMovement Sciences, University of Verona, Verona, Italy e-mail: francesco.amaddeo@univr.it G. Andrews CRUfAD, UNSW at St Vincent’s Hospital, Darlinghurst, NSW, Australia e-mail: gavina@unsw.edu.au # Springer Science+Business Media Singapore 2017 N. Okkels et al. (eds.), Mental Health and Illness in the City, Mental Health and Illness Worldwide, https://doi.org/10.1007/978-981-10-2327-9_19 223 and religions. This chapter reports of several promising community care initiatives and evidence that the era of institutionalization may be ending.
Nordic Journal of Psychiatry, 2020
Background: Network analysis provides a new viewpoint that explicates intertwined and interrelate... more Background: Network analysis provides a new viewpoint that explicates intertwined and interrelated symptoms into dynamic causal architectures of symptom clusters. This is a process called 'symptomics' and is concurrently applied to various areas of symptomatology. Aims: Using the data from Research on Asian Psychotropic Prescription Patterns for Antipsychotics (REAP-AP), we aimed to estimate a network model of extrapyramidal syndrome in patients with schizophrenia. Methods: Using data from REAP-AP, extrapyramidal symptoms of 1046 Asian patients with schizophrenia were evaluated using the nine items of the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The estimated network of the ordered-categorical DIEPSS items consisted of nodes (symptoms) and edges (interconnections). A community detection algorithm was also used to identify distinctive symptom clusters, and correlation stability coefficients were used to evaluate the centrality stability. Results: An interpretable level of node strength centrality was ensured with a correlation coefficient. An estimated network of extrapyramidal syndrome showed that 26 (72.2%) of all possible 35 edges were estimated to be greater than zero. Dyskinesia was most centrally situated within the estimated network. In addition, earlier antipsychotic-induced extrapyramidal symptoms were divided into three distinctive clustersextrapyramidal syndrome without parkinsonism, postural instability and gait difficulty-dominant parkinsonism, and tremor-dominant parkinsonism. Conclusions: Our findings showed that dyskinesia is the most central domain in an estimated network structure of extrapyramidal syndrome in Asian patients with schizophrenia. These findings are consistent with the speculation that acute dystonia, akathisia, and parkinsonism could be the risk factors of tardive dyskinesia.
The Kaohsiung journal of medical sciences, 2018
Our study aimed to assess the psychometric validity of the conceptual disorganization item and ot... more Our study aimed to assess the psychometric validity of the conceptual disorganization item and other items of the Brief Psychiatric Rating Scale (BPRS) for detecting disorganized speech in patients with schizophrenia. We included 357 schizophrenia patients with disorganized speech and 1082 without disorganized speech from the survey centers in India, Indonesia, Japan, Malaysia, and Taiwan, using the data from the Research on Asian Psychotropic Patterns for Antipsychotics (REAP-AP) study. After adjusting the effects of confounding variables, a binary logistic regression model was fitted to identify BPRS items independently associated with disorganized speech. Receiver operating characteristic (ROC) curves were used to identify optimum cut-off scores and their sensitivities and specificities for detecting disorganized speech. After adjusting the effects of confounding variables, the fitted binary logistic regression model indicated that conceptual disorganization (P < 0.0001), unco...
High Dose Antipsychotic Use in Schizophrenia: Findings of the REAP (Research on East Asia Psychotropic Prescriptions) Study
Pharmacopsychiatry, 2004
High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equ... more High-dose antipsychotic regimes (defined as the prescription of more than 1000 chlorpromazine-equivalents milligrams of antipsychotic per day) in the management of patients with schizophrenia are not uncommon, but most reports are from western countries. Recent functional neuroimaging studies have found that the previous notion concerning the use of antipsychotic medication, especially in high doses, was unsupported and untenable. This international study examined the use of high dose antipsychotic medication and its clinical correlates in schizophrenia patients within six East Asian countries/territories. Within the study group (n = 2399), 430 patients (17.9%) were prescribed high dose antipsychotics. Antipsychotic use varied significantly between countries, with Japan, Korea, and Singapore using higher doses than the other countries. High dose antipsychotic use was associated with younger age in Japan (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001), longer duration of admission (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001), duration of illness (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001, particularly in Korea and Taiwan), positive psychotic symptoms (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.001, particularly in Japan and Korea), and aggression (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.05, particularly in Japan), and also with a higher likelihood of extrapyramidal and autonomic adverse effects (p &amp;amp;amp;amp;amp;amp;amp;lt; 0.05, particularly in China). Country, younger age, the presence of delusions and disorganized speech, polypharmacy, and receiving depot medication but not atypical antipsychotic drugs were important predictors of high antipsychotic use. This survey revealed that high antipsychotic dosing is not an uncommon practice in East Asia. It behooves the prescribing clinicians to constantly reevaluate the rationale for such a practice.
International Clinical Psychopharmacology, 2001
Ensuring safety of pharmaceuticals is one of the most important objectives of the Pharmaceutical ... more Ensuring safety of pharmaceuticals is one of the most important objectives of the Pharmaceutical Affairs Law. Safety information obtained by the approval is limited because size of the subjects in clinical trials is small and factors on subjects such as concomitant use of other drugs are controlled. Therefore, safety of pharmaceuticals is ensured through information obtained during long postmarketing periods. Under the Law, the manufacturers shall report to the Ministry once they know a certain category of safety information. Also, the Ministry has a system by which medical professionals can directly report safety information. Ž . In PMS Post-Marketing Surveillance , the collection of safety information in early stages of the sale of new drug has an extremely important meaning. During a short period of time after the launch, the number of patients prescribed will dramatically increase and the drug is administered to diverse patients with different backgrounds. This is the period when important adverse reactions are discovered that have not been detected during the development stage. MoHW considers introducing ''Early Post Marketing Phase Vigilance'' in order to collect information on serious adverse reactions thoroughly that may come out just after the launch and to take necessary measures as soon as possible.