Yap regulates skeletal muscle fatty acid oxidation and adiposity in metabolic disease.

Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.

Twelve-nucleotide repeat polymorphism of D4 dopamine receptor gene in Chinese familial schizophrenic patients.

BACKGROUND: Disturbances in dopaminergic transmission have been implicated in the etiology of schizophrenia. Catalano et al reported an association between delusional disorder and the number of a 12-nucleotide (bp) repeat sequence in the first exon of dopamine D4 receptor gene (DRD4), which indicated a possible role of this polymorphism in the pathogenesis of psychotic disorders. METHODS: DNA of 42 Chinese controls, 50 sporadic schizophrenic patients, and 30 familial schizophrenic probands were collected. Genotype of the 12-bp repeat polymorphism of DRD4 was determined with polymerase chain reaction and agarose gel electrophoresis. Genotypic and allelic frequencies were compared among the three groups using the chi-square test. RESULTS: Forty-three (86%) sporadic schizophrenic patients, 25 (83.3%) familial schizophrenic probands, and 35 (83.3%) controls were A1 (two 12-bp repeat) homozygotes. One (2.0%) sporadic schizophrenic and 1 familial schizophrenic patient were A2 (one 12-bp repeat) homozygotes. There was no significant difference in allelic and genotypic distributions among the three groups. CONCLUSIONS: The present data do not support an association between schizophrenia and any specific allele of the 12-bp repeat polymorphism of DRD4. Significance of familial/sporadic division of schizophrenia cannot be supported regarding this repeat polymorphism.

Epsilon 4 allele of apolipoprotein E increases risk of Alzheimer's disease in a Chinese population.

We examined the apolipoprotein E genotype in 56 Chinese patients with late-onset sporadic Alzheimer's disease (AD) and 57 Chinese control subjects of similar age. The frequency of epsilon 4 in the AD group was significantly higher than that in the control group (23.2% versus 7.9%, p = 0.003). The odds ratio for AD in individuals with either one or two epsilon 4 was 2.96 (95% CI 1.11 to 8.03). The linear trend for AD in proportion to alleles of epsilon 4 was also significant (chi 2 = 8.2, p = 0.004). Our results support the association between epsilon 4 and AD in the Chinese.

Effects of repeated high-dose methamphetamine on local cerebral glucose utilization in rats.

Repeated administration of high doses of methamphetamine (MAP) to rats can induce long-lasting neurotoxicity which may be related to permanent psychotic symptoms and negative symptoms in some MAP psychotic patients. In this study, we used the 2-[14C]deoxyglucose (2DG) method to analyze the effects of repeated MAP administration (12.5 mg/kg, i.p., 4 times every 2 hr within a day) 14 days and 60 days after drug administration. The results showed a widespread (26 of the 43 regions examined) decreases in the regional cerebral glucose utilization. The regions with decrease metabolism included all the extrapyramidal systems, the hippocampus formation and dorsal raphe nucleus. Rats tested 60 days after drug administration has similar finding to those with a 14-day abstinent period. The results of the functional change in this study provide support for the neurotoxic effects of repeated high dose MAP administration in rats. Furthermore, the neurotoxic effects are selective and long-lasting. We suggested the MAP neurotoxic model can be used to study the permanent psychosis and negative symptoms of MAP-induced psychosis in humans.

Dopamine D4 receptor variants in Chinese sporadic and familial schizophrenics.

Variation in the number of tandem repeats of a 48 base pair (bp) unit was found in the gene of the dopamine D4 receptor (DRD4). The number of repetitions of the 48bp unit was shown to influence the binding of clozapine, which suggests that different alleles may function differently in vivo and affect the pathogenesis of schizophrenia. Genotypes of DRD4 polymorphism were analyzed for 47 schizophrenic probands who had at least one living sibling with a diagnosis of schizophrenia, 35 unaffected siblings of the schizophrenic proband, 42 sporadic schizophrenic patients, and 43 healthy controls without a family history of psychosis. There was no significant difference in genotypic or allelic distributions among the four groups. Significant differences in the frequencies of two- and seven-repeats alleles between the Chinese and Caucasians controls were noted. The present study did not support that a particular allele or genotype of the 48bp-repeat of DRD4 was associated with schizophrenia.

No evidence for association of serotonin-2A receptor variant (102T/C) with schizophrenia or clozapine response in a Chinese population.

The serotonin hypothesis in schizophrenia had regained interest with the superior efficacy of clozapine in the refractory schizophrenic patients. Among the serotonin receptors, the serotonin 2A (5HT2A) receptor subtype is the most widely studied. Previous studies on the association between a silent mutation polymorphism of the 5HT2A gene (102T/C) and schizophrenia or clozapine response have yielded conflicting findings. Therefore, we investigated whether these genetic variants of the 5HT2A receptor are associated with schizophrenia or with response to clozapine treatment in a Chinese population. Ninety-seven schizophrenic patients and 101 control subjects were included in the study. The receptor variants were found at similar frequencies in schizophrenic patients and healthy control subjects. Also, we did not find the variants to influence the response to clozapine in schizophrenic patients. We suggest that the assessment method of clozapine response and the ethnicity may influence the result.

Effects of amphetamine challenge on local cerebral glucose utilization after chronic dopamine D1 and D2 receptor agonist administration to rats.

Repeated amphetamine administration can cause an augmentation of regional cerebral metabolic activity. This study analyzed the regional cerebral metabolic changes which occurred in rats after pretreatment with the selective dopamine D1 and D2 receptor agonists, (+/-)SKF 38393 ((+/-)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine HCl) and quinpirole (trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo(3, 4-g)quinoline), as measured by the 2-[14C]deoxyglucose method. The results showed selective metabolic augmentation in rats pretreated with SKF 38393 but not in those pretreated with quinpirole alone or with quinpirole in combination with SKF 38393. These findings demonstrated that dopamine D1 receptors may play a critical role in the development of metabolic augmentation after repeated stimulant administration.

The effect of acute administration of risperidone on local cerebral glucose utilization in the rat.

Risperidone (R 64 766, 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-pyperidinyl]ethyl )-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one) has superior effects in treating negative symptoms of schizophrenia and causes less extrapyramidal side effects than traditional antipsychotics. In this study, we employed the [14C]2-deoxy-D-glucose method to map local cerebral metabolic activity of rats acutely administrated i.p. with 0.0, 0.1, 0.5, 1.0 and 2.0 mg kg(-1) risperidone. Risperidone in the highest dose produced a reduction of glucose utilization in 11 of the 38 regions examined. The results showed that the regions with metabolic change are somewhat different from those results studied with microdialysis and the Fos immunohistochemistry. Among the nuclei with metabolic changes, the hippocampus and the mediodorsal nucleus of the thalamus may be related to the therapeutic action of risperidone and require further study.

A double-blind comparative study of clozapine versus chlorpromazine on Chinese patients with treatment-refractory schizophrenia.

Clozapine has been shown to have superior effectiveness compared with classic neuroleptics in treating refractory schizophrenia in Caucasians, but its efficacy and safety in Chinese have not been adequately studied. Forty Chinese schizophrenic patients were recruited in a 12-week, double-blind, comparative trial. Twenty-one patients were randomly assigned to clozapine treatment and 19 to chlorpromazine treatment. The average dose was 543 +/- 157 and 1163 +/- 228 mg/day for clozapine and chlorpromazine, respectively. The results showed that six clozapine-treated patients (28.6%) had more than 20% improvement in Brief Psychiatric Rating Scale score and were classified as responders, whereas none of the chlorpromazine-treated patients was classified as a responder. The degree of improvement in positive symptoms, negative symptoms and Brief Psychiatric Rating Scale scores in the clozapine group was inversely correlated with the severity of negative symptoms at entry into the trial. Two clozapine-treated patients were withdrawn from the study, one because of leukopenia and nausea, and the other because of vomiting and hypotension. Chlorpromazine treatment was prematurely discontinued in two patients, because of jaundice and over sedation in one, and because of severe weight loss in the other (9 kg). The rate of moderate-to-severe sialorrhea was high in clozapine-treated patients (28.6%). Two clozapine-treated patients and two chlorpromazine-treated patients showed significant improvement in previously existing tardive dyskinesia and one chlorpromazine-treated patient exhibited aggravation of tardive dyskinesia. The results of this study indicate that clozapine treatment might have advantages over chlorpromazine for Chinese schizophrenic patients who are refractory to typical neuroleptic treatment.

Alterations in local cerebral glucose utilization in rats after chronic amphetamine administration without subsequent challenge.

The 2-deoxyglucose (2-DG) method was used to study regional metabolic changes in rats following chronic d-amphetamine treatment without subsequent challenges. Four groups of rats were pretreated (intraperitoneal administration) with d-amphetamine (0, 1, 5, or 10 mg/kg) once per day for 14 days. After a 7-day abstinence period without further challenge, the 2-DG method was used to measure the rates of local cerebral glucose utilization (LCGU). Significant metabolic changes among the four groups were found in five brain regions, including the nucleus accumbens and the lateral habenular nucleus. Another four groups of rats with the same pretreatment regimens, challenged with 5 mg/kg d-amphetamine, were used for behavioral testing. The results showed intense stereotyped behaviors in the 5 mg/kg and the 10 mg/kg groups. In the steady state, however, there were no significant glucose utilization changes in the nigrostriatal system, which is thought to be related to stereotyped behaviors. During steady state, metabolic changes were found in a limited number of brain regions. No difference in LCGU was found in the sensitization-related regions. Further challenges with stimulants may be necessary to investigate the metabolic responses after sensitization.

Effects of acupuncture on serum cortisol level and dopamine beta-hydroxylase activity in normal Chinese.

Serum cortisol levels were determined in 40 normal Chinese and dopamine beta-hydroxylase activities were measured in 22 normal subjects before and after acupuncture treatment. All subjects were studied twice with an interval of one week or more. In the self-control study, the subjects were needled at 5 non-acupuncture loci. In the experimental study, they were needled at the following 5 traditional acupuncture loci--right side GB-20, both sides EH-6, and both sides St-36. Blood samples were withdrawn before acupuncture and 15 and 45 min. after acupuncture. No change of serum dopamine beta-hydroxylase activity was observed. Serum cortisol levels increased significantly after needling on the traditional acupuncture loci. After acupuncture for 15 and 45 min., the cortisol increase was 28 and 50%, respectively, as compared to the self-control studies. The beneficial effect of acupuncture in the treatment of functional disorders, therefore, may be mediated by cortisol or other hormones and neurohormones.

Analysis of drug abuse among adolescent psychiatric inpatients at Veterans General Hospital-Taipei.

BACKGROUND: The problems of drug abuse has been growing rapidly in Taiwan area recently. Adolescents hospitalized due to drugs related problems were a special population and research of this population may contribute to the whole view of the drug abuse problems in our society. METHODS: Psychiatric inpatient records of Veterans General Hospital-Taipei from January, 1991 to June, 1993 were reviewed. Among totally 296 admissions of 260 adolescents, 38 admissions of 27 adolescents were related to drug abuse. The discharge diagnosis, urine drug screen test during admission, hospitalization course, follow-up condition of the 38 admissions as well as the demographic data, pattern of drug abuse, family and personal problems of the 27 adolescents were collected and analyzed. RESULTS: Among the 27 patients, 21 (78%) abused amphetamine only or mainly, and 14 (52%) of them also drank alcohol daily. As a whole, they began to drink at age 15.6 +/- 1.5 years, to abuse amphetamine at 16.8 +/- 1.2 years. Those who sniff glue started at the age of 15.4 +/- 1.8 years and those who abuse heroin started at the age of 18 years. 14 patients (51%) had previous abstinence history, and the most common reason of failure were craving, peer pressure and boredom. Personal and family factors were the major difficulties encountered in the process of abstinence, according to the evaluation of their incharge doctors. 16 (59%) of them had definite family problems, including loss of parent(s), marital discord or inconsistent attitude of parents, and psychotic history of mother. Interestingly, 15 (56%) of the patients were the youngest, 5 (18%) were the only sons and only 3 (11%) were the eldest in their family. Among the 38 admissions, 34 (89%) were diagnosed as "organic delusional disorder", or "organic hallucinosis" by DSM-III-R criteria. CONCLUSIONS: Amphetamine has become one of the most popular drugs of abuse in Taiwan area in recent years. Many drugs of abuse in Taiwan area 10 years ago were not found in this study. Because of the psychidelic effect of amphetamine, many amphetamine abusers were hospitalized and the drug abusers among adolescent psychiatric inpatients have increased almost 5 times in the past 10 years. Family problems played a significant role. Family approach would thus be very important in prevention, treatment and rehabilitation of the adolescent drug abusers.

[Characteristics of elderly patients admitted to the psychiatric ward of a general hospital].

The rapid growth of the over 65 population in Taiwan during recent decades has brought into focus the planning to provide health care for aged citizens. It is generally agreed that the incidence of mental disorders rises with age. With the stress on rapid treatment and early return to community, the concept of short-term hospitalization for the geropsychiatric patients has become more accepted. In this study we examined characteristics, diagnostic classification and treatment outcomes of 524 consecutive patients (age > or = 65) admitted to the geropsychiatric unit of a general hospital over a 5-year period. Results demonstrated that 45.9% of the patients had organic mental disorders. Among them, almost half of the patients were diagnosed as having dementia; delirium was the second most common diagnosis. The average length of stay was 26.7 days for all patients and it was not affected by diagnostic subtype. No significance was found in the length of stay between the geropsychiatric inpatients and the other psychiatric inpatients. Outcomes measure showed favorable response to hospitalization in most of these patients. These data suggested that there is a specific diagnostic distribution in the geropsychiatric inpatients. Rigorous organic work-up in these patients is necessary to rule out organic problems. The favorable response after short-term hospitalization indicated the restorative and rehabilitative functions of the general hospital geropsychiatric care. The hospital's fears of being burdened with a chronic population could be lessened with a suitable referral system. Further study is needed to explore whether early geropsychiatric intervention may obviate the need for admission or reduce the length of stay.

In search of a status for acupuncture.

Acupuncture treatment is currently generating increased interest in various parts of the world. The effectiveness of this quasi-medical procedure, which has survived for almost 5 000 years, is considered on the strength of statistical data obtained at an institution where such treatment is applied under acceptable scientific circumstances. Explanations are sought for the encompassing extent of treatment claims and the continued support for this technique which is often subjected to severe criticism in modern contexts. The roles of literacy, tradition and convention, a placebo effect and psychological factors as explanatory agents are discussed. The procedure also has possible psychophysical and physiological foundations which sufficiently warrant further scientific effort to find an explanation for this phenomenon.

Psychiatric consultations in pediatric inpatients.

Emotional problems are not uncommon in hospitalized children. The authors reviewed psychiatric consultations on a pediatric ward in a medical center and compared the findings with a non-pediatric group and the Western reports. Forty consultations were requested in a three-year period which represented 0.35% of all admissions to pediatric ward and 1.0% of all psychiatric consultations in that period. The consultation rate of the pediatric ward is significantly lower than that of the non-pediatric wards. The most common reason for the referrals was for the evaluation of possible psychopathogeneses from unexplained physical symptoms. A wide range of psychiatric diagnoses were found. Among them, adjustment disorders, anxiety or somatoform disorders, diagnosis deferred and no psychiatric diagnosis were the most commonly made. Pediatric patients had a similar percentage diagnosis of adjustment disorders compared with the non-pediatric group but far less organic mental disorders. Besides medication, psychological and family intervention were frequently recommended by the psychiatrists. These findings suggest that there were unique psychological characteristics in the hospitalized children which required specialists and further studies. It is hoped that increasing the collaboration between pediatricians and psychiatrists can improve the medical care of these sick children.

Organic delusional disorder in psychiatric in-patients: comparison with delusional disorder.

Organic delusional disorder (ODD) is rarely diagnosed in psychiatric in-patients, and may be misdiagnosed as delusional disorder (DD) from a similar clinical presentation. The aim of the present study was to investigate the characteristics of ODD and to make a comparison with those of DD patients. Patients who conformed to DSM-III-R criteria for ODD were recruited from an 8-year psychiatric in-patient database. Matching controls were DD patients admitted over the same time period. The prevalence of ODD according to DSM-III-R criteria was 0.4% of total admissions and 2.9% of organic mental disorders. Compared to DD patients, ODD patients less often had a family psychiatric history, and had an older age of onset of psychiatric disorder, longer hospital stays and lower treatment dosage of antipsychotic drugs. It is suggested that a detailed medical history and examination are needed in patients with delusion, especially in patients with a late onset of psychiatric symptoms and no family psychiatric history.

[Psychiatric emergency consultation in a general hospital].

Inpatients in general hospital often presented with psychological problems and some of them need emergent psychiatric interventions. However, there have been little attention on the psychiatric emergency consultation. The purpose of this paper is to review the psychiatric emergency service in a general hospital over 3-year period. During this period, there were 88 psychiatric emergency consultations that represented 2.3% of all psychiatric consultations. The emergency group showed no difference in sex and age, but received more diagnoses of delirium (58.0%) than the other referrals. About one fourth of these patients had psychiatric history. Stated requests for "agitation and irritability", "psychiatric symptoms" and "uncooperation with treatment" were the most frequent reasons. Sixty-five percent of the patients receive recommendations of medication treatment. Among them, neuroleptics and anxiolytics were most common used. About one half of the patients needed further medical tests. After psychiatric interventions, most of the patients got improved within 2 days but 15 patients died during hospitalization. These findings indicated that psychiatric emergency consultation though the request rate is low. When making diagnoses in emergency consultation, past psychiatric history is important and organic mental disorders should be ruled out first. After psychiatric interventions, most of the psychiatric emergency could be improved. It suggested that the setting of psychiatric emergency consultation could improve the quality of patient care in a ageneral hospital.

Psychiatric consultations in obstetric inpatients.

OBJECTIVE: The purpose of this study was to investigate the psychiatric consultation condition in the obstetric ward with particular attention paid to the reasons for referral, psychiatric diagnoses and recommendations. METHODS: This study was conducted in a medical center with 73 obstetric beds. All psychiatric consultations of obstetric inpatients during a 3-year period were included in this study. Data were derived from clinical charts and consultation records that included demographic data, reasons for referral, psychiatric diagnoses and treatment recommendations. RESULTS: Within the 3-year period, 28 patients were referred for psychiatric consultation, or 0.3% of the 9,972 obstetric admissions. The obstetric group represented 0.7% of all the psychiatric consultations. The most common reason for the referral was anxiety. Many obstetric problems, medical histories and psychiatric histories were found in these 28 patients. The most common diagnoses were depression or dysthymia, and schizophrenia. The diagnosis of organic mental disorders was rarely found. The vast majority of the psychiatric consultants were likely to recommend medication and psychological intervention. CONCLUSION: Even though there is a low psychiatric consultation rate among the obstetric inpatients, it does not mean that the prevalence rate of mental disorders is low in the obstetric patients. Psychiatric problems may be neglected or happen after patients are discharged. Organic mental disorders were rarely found in the obstetric patients which suggested a different pattern of mental disorders in the obstetric patients compared to other patients. The stress during child delivery needs further study for it may exacerbate or predispose a mental disorder. It is suggested that collaboration between obstetric staff and the consultation-liaison psychiatrists may provide better care for pregnant women patients.

The effect of panic attack on mitral valve prolapse.

It has been reported that panic attacks might cause mitral valve prolapse (MVP) via haemodynamic or indirect effects. Such prolapse can be classified as being physiological (benign course) or pathological (poor course). It is therefore important to consider whether panic attacks, as a risk factor for MVP, are associated with its physiological or pathological type. Our study sample consisted of two groups of patients with panic disorder (PD), one having onset within 1 year (n=24) and the other with a history of more than 10 years (n=21). Demographic data, symptom presentations, auscultatory and echocardiographic findings of both groups were compared, but no significant difference was found except with regard to anticipatory anxiety. It is concluded that panic attack exerts no significant effect on mitral valve prolapse.