Hsien-Jane Chiu

Incidence and Risk Factors of Workplace Violence on Nursing Staffs Caring for Chronic Psychiatric Patients in Taiwan

This one-year follow-up study determined the incidence and risk factors of workplace violence against nursing staff in a psychiatric hospital. The cohort members had a website to report events whenever they came across violence. A total of 971 events were reported. The incidence rates of physical violence, verbal abuse, bullying/mobbing, sexual harassment, and racial harassment were 1.7, 3.7, 0.2, 0.3, and 0 per staff-year, respectively. Young age, female sex, lower education, shorter duration of employment, and high level of anxiety of staff seemed to be the determinants of violence. Pre-placement education should focus on these staff to reduce workplace violence.

ADRA1A gene is associated with BMI in chronic schizophrenia patients exposed to antipsychotics

Noradrenaline and adrenaline are neurotransmitters of the sympathetic nervous system that interact with various adrenergic receptor (ADR) subtypes, and this regulates the basal metabolic rate, thermogenesis and efficiency of energy utilization. We examined a possible role of the gene coding for ADRA1A receptor in weight gain in schizophrenia subjects exposed to antipsychotics. A total of 401 schizophrenia in-patients treated with antipsychotics for >2 years were recruited and a final 394 DNA samples were genotyped. Their body mass indexes (BMIs) were recorded for 12 months and parameterized to be correlated in regression. Among the 58 single-nucleotide polymorphisms (SNPs) genotyped, 44 valid SNPs, which had minor allele frequency ⩾0.03, were analyzed in statistics. Linear regression model with age, gender, diabetes, use of typical antipsychotics and use of atypical antipsychotics as covariates, with or without gender interaction, showed evidence of associations between the ADRA1A gene and BMI. Most of the SNPs associated with BMI are located in the promoter and intron regions, and being female appeared to enhance the gene effect. Our study suggests that the ADRA1A gene is involved in weight gain among schizophrenia patients treated with antipsychotics. Further molecular dissection of the ADRA1A gene warrants better understanding on weight gain mechanisms in schizophrenia.

Association of the ADRA1A gene and the severity of metabolic abnormalities in patients with schizophrenia

Patients with schizophrenia have a higher risk of developing metabolic abnormalities and their associated diseases. Some studies found that the accumulative number of metabolic syndrome components was associated with the severity of metabolic abnormalities. The purpose of this study was to examine the roles of the ADRA1A, ADRA2A, ADRB3, and 5HT2A genes in the risk of having more severe metabolic abnormalities among patients with schizophrenia. We studied a sample of 232 chronic inpatients with schizophrenia (120 males and 112 females) to explore the associations between the four candidate genes and the severity of metabolic syndrome by accumulative number of the components. Four single nucleotide polymorphisms in the candidate genes were genotyped, including the Arg347Cys in ADRA1A, the C1291G in ADRA2A, the Try64Arg in ADRB3, and the T102C in 5HT2A. An association between the accumulative number of metabolic syndrome components and the ADRA1A gene was found after adjusting age, sex, and other related variables (p-value=0.036). Presence of the Arg347 allele in the ADRA1A gene is a risk factor for having more severe metabolic abnormalities. These findings suggest a medical attention of closely monitoring metabolic risks for schizophrenia patients with high-risk genotypes.

Severity of psychosis syndrome and change of metabolic abnormality in chronic schizophrenia patients: Severe negative syndrome may be related to a distinct lipid pathophysiology

BACKGROUND Metabolic abnormality is common among schizophrenia patients. Some metabolic traits were found associated with subgroups of schizophrenia patients. OBJECTIVES We examined a possible relationship between metabolic abnormality and psychosis profile in schizophrenia patients. METHOD Three hundred and seventy-two chronic schizophrenia patients treated with antipsychotics for more than 2 years were assessed with the Positive and Negative Syndrome Scale. A set of metabolic traits was measured at scheduled checkpoints between October 2004 and September 2006. RESULTS Multiple regressions adjusted for sex showed negative correlations between body mass index (BMI) and total score and all subscales; triglycerides (TG) was negatively correlated with total score and negative syndrome, while HDLC was positively correlated with negative syndrome. When sex interaction was concerned, total score was negatively correlated with BMI but not with others; negative syndrome was negatively correlated with BMI and positively with HDLC. No metabolic traits were correlated with positive syndrome or general psychopathology. CONCLUSIONS Loss of body weight is a serious health problem in schizophrenia patients with severe psychosis syndrome, especially the negative syndrome. Schizophrenia patients with severe negative syndrome may have a distinct lipid pathophysiology in comparison with those who were less severe in the domain.

The quantitative detection of aripiprazole and its main metabolite by using capillary-electrophoresis

Background: We aimed to establish a feasible and reliable method to measure the level of aripiprazole and its main metabolite, dehydroaripiprazole, using a capillary‐electrophoresis (CE) machine. Methods: Two blood samples were obtained from psychiatric patients hospitalized in Yu‐Li Hospital who had been treated with aripiprazole for more than 4 weeks, at least 10 mg/d. Conditions for voltage, temperature and buffer concentration was optimized on a CE machine. Results: The most optimal conditions for CE were 80 mM 2–3% DMSO‐phosphate as a buffer under pH = 3.0, 15 KV, 20°C and a detection wavelength of 214 nm. The linear ranges of aripiprazole and dehydroaripiprazole concentration were from 0.5 to 50 ng/mL. Conclusion: CE method is a feasible method to measure aripiprazole level with relatively low price compared with other analytical techniques for clinical use.

Prevalence of hepatitis B and hepatitis C in patients with chronic schizophrenia living in institutions

Background: Preventing and managing hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is an important public health issue worldwide, and Taiwan is one of the countries where viral hepatitis is most endemic. Previous studies have shown that patients with serious mental illnesses have a higher risk for hepatitis infection. We investigated the prevalence of HBV and HCV among institutionalized patients with chronic schizophrenia in Taiwan. Methods: A total of 590 patients were recruited into the study. HBV surface antigen, HCV antibody, and liver function were determined for all participants. Results: The seroprevalence of HBV surface antigen was 10.4% (males 12.6%, females 7.0%), and that of anti‐HCV was 1.9% (males 2.6%, females 0.8%). Conclusion: Our study showed that the prevalences of HBV and HCV among institutionalized patients with chronic schizophrenia were no higher than the prevalences in the general population in Taiwan. The commodious environment and medical resources of the hospital where the patients were living might have prevented an elevation of HBV and HCV infection in those with schizophrenia, supplementing the continuing benefits from the HBV vaccination that was introduced in 1984.

Significance of morphological features in schizophrenia of a Chinese population.

Neuro-developmental hypothesis suggests that schizophrenia is originated from aberrant brain development during first and/or early trimester of gestation. Accordingly, when a schizophrenia gene is involved in the regulation of embryonic development and continues to play a role in the later life, it may result in the co-occurrence of defective organ systems and/or physiological functions with schizophrenia. We proposed a checklist with 13 morphological features and examine their prevalence rates in 151 schizophrenic patients and 151 controls. Statistical analyses showed that single transverse palmar crease, head circumference, covered epicanthus, finger length difference, and inner canthus distance, made significant contributions to schizophrenia. To rule out the age confounding effects on morphological features, we dropped older schizophrenic subjects and younger controls in further regression analysis. The regression model correctly classified 82.8% of control subjects (specificity) and 86.4% of schizophrenic patients (sensitivity), and provided an overall successful classification rate of 84.5%, with single transverse palmar crease on the first rank. The association of morphological features and schizophrenia is probably genetic in origin, as specific morphological features were more frequent in non-affected parents with higher genetic loading of schizophrenia. In addition, the association of finger length difference in schizophrenia found in this study has never been reported elsewhere. Our study showed that five out of 13 morphological features in the propose checklist may be used as biomarkers for schizophrenia, either for clinical practice or research purposes.

Increase of incidence of impaired fasting glucose in young schizophrenia patients

METACHROMATIC LEUKODYSTROPHY (MLD) is an autosomal recessive disease caused by a mutation in the arylsulfatase A (ASA) gene. The possibility of MLD in middleaged patients is seldom entertained because most cases of MLD are of late-infantile onset. We report a 59-year-old man with adult-onset MLD, which suggests that MLD should be considered in the differential diagnosis of presenile dementia. The patient’s developmental milestones were normal. At age 50, he began to have some difficulty at his job. When the patient first visited our hospital at age 52, he was polite and cooperative but deficient in concentration and attention. Wechsler Adult Intelligence Scale–Revised (WAIS–R) fullscale IQ was 61 (Verbal IQ 67, Performance IQ 63). Brain magnetic resonance imaging showed diffuse cerebral white matter involvement, most prominent in the frontal lobes, as well as diffuse cortical atrophy and thinning of the corpus callosum. At age 53, he developed urinary incontinence, dressing apraxia, and personality changes including hypospontaneity, dysphoria, and bursts of aggression. At age 54, he exhibited apathy, agraphia and bradykinesia. He had pes cavus and a broad-based gate. Neurological examination revealed snout reflex, palmomental reflex, and frontal ataxia, all of which suggest frontal lobe involvement. In the lower limbs, tendon reflexes were weak, and deep sensation was reduced. Conduction velocity of the median nerve was reduced to 21.1 m/sec. Disorientation to time and place, and severe impairment of attention and working memory were obvious. WAIS-R full-scale IQ was 47 (Verbal IQ 63, Performance IQ < 46). Electroencephalography showed a slow basic rhythm, with focal delta waves over the bilateral frontal and temporal regions. Single photon emission computed tomography with Tc-99m ethyl-cysteinate dimer revealed decreased regional blood flow in the bilateral frontal and temporal lobes. The cerebrospinal fluid had a protein concentration of 172 mg/dl. The level of leukocyte ASA activity was low at 10.7 nmol/mg protein/hr. Urinary sulfatides were not detected. A molecular genetic study showed a compound of two mutations in the ASA gene, the L289S and the T409I mutation. At the time of writing the patient, aged 59, exhibits akinetic mutism with occasional epileptic seizures. The bradykinesia, gait disturbance, and personality changes including blunted affect, apathy, and bursts of aggressiveness are consistent with features of subcortical dementia. These manifestations differ from those of cortical dementia such as Alzheimer’s disease. The onset of adult MLD generally occurs in the second or third decade of life. The case reported herein represents the latest onset of MLD in Japan, suggesting that as long as progressive dementia with white matter abnormality is present, the possibility of MLD should be considered, regardless of the patient’s age. REFERENCES

A positive association between homeostasis model assessment of insulin resistance score and the Trp64Arg polymorphism of the β3-Adrenergic receptor gene in schizophrenia patients in Taiwan.

OBJECTIVE To investigate the possible association between the Trp64Arg polymorphism of the β3-adrenergic receptor gene and the homeostasis model assessment of insulin resistance (HOMA-IR) index in schizophrenia patients in Taiwan. METHOD A total of 203 inpatients who met DSM-IV diagnostic criteria for schizophrenia were recruited from a psychiatry center in Taiwan from September 2002 to August 2003. All patients had been treated with antipsychotics for at least 6 months. The genotyping of the Trp64Arg polymorphism of the β3-adrenergic receptor gene was done by the polymerase chain reaction-restriction fragment length polymorphism method with the restriction enzyme MvaI. The HOMA-IR index was used to indicate the degree of insulin resistance. RESULTS After adjusting for sex, age, and body mass index status, the association between the HOMA-IR index and the Trp64Arg polymorphism of the β3-adrenergic receptor gene was still positive (regression coefficient = -0.65, P = .033). CONCLUSIONS The polymorphism of the β3-adrenergic receptor gene may be related to the development of insulin resistance in chronic schizophrenia patients in Taiwan.

DNA paternity test resolving refractory Capgras syndrome

CAPGRAS SYNDROME IS characterized by a delusional belief that a close person has been replaced by an imposter. Some patients with this unusual syndrome demonstrate limited responses to pharmacotherapy or electroconvulsive therapy. However, further treatment strategies are rarely discussed for this refractory population. Currently the DNA paternity test is the gold standard for identification of biological paternity. We report a patient with refractory Capgras syndrome, which resolved after the introduction of a DNA paternity test. A 27-year-old, single, high-school-educated Taiwanese man suffered from Capgras syndrome from the age of 24 years. He believed that his uncle was impersonating his father, and had murdered his real father and grandfather, and then seduced and married his mother. The mental status examination was normal except for this systemic delusion. His extroverted and amiable premorbid personality and fair premorbid interpersonal relationships excluded cluster A personality traits. Intelligence tests revealed a full IQ of 84. The diagnosis of delusional disorder was made by two psychiatric specialists. Such delusion did not respond to two antipsychotic agents (15 mg/day of haloperidol and then 4 mg/day of risperidone, doses were not increased due to intolerance of side-effects). Therefore, the patient had been hospitalized for 4 months because of persistent risk of violence toward his parents. After negotiating with his family and his psychiatric doctor, the patient requested to undergo a DNA paternity test. His delusion resolved soon after the result proved their parentage. After 9 months of follow up, the dose of risperidone was tapered to 1 mg, and his condition remained stable. The patient provided informed consent for this paper. Studies suggest that the DNA paternity test has at least 99.9% probability of paternity for not exclusion or 100% certainty of exclusion. Given the wide acknowledgement of strong credibility to settle legal disputes, it is generally trusted by people, especially in Taiwan, where it is frequently presented in local television soap operas. As demonstrated in this case, the DNA paternity test can serve as an effective adjunctive management for refractory Capgras syndrome when used on appropriate occasions. Several practical issues regarding procedures, appropriate time, criteria for eligible patients, and possible adverse effects need further investigation. For example, our patient had a monosymptomatic delusion and had received a full-course antipsychotic treatment, thus might benefit because of less impairment in reality testing. This adjunctive management should be limited to refractory patients that have already received treatment, initiated by the patients’ will, and performed after a careful evaluation to exclude delusion-based requests. More case studies are warranted in the future.