Tsuo-Hung Lan

Bone mass in schizophrenia and normal populations across different decades of life

BackgroundChronic schizophrenic patients have been reported as having higher osteoporosis prevalence. Survey the bone mass among schizophrenic patients and compare with that of the local community population and reported data of the same country to figure out the distribution of bone mass among schizophrenic patients.Methods965 schizophrenic patients aged 20 years and over in Yuli Veterans Hospital and 405 members aged 20 and over of the community living in the same town as the institute received bone mass examination by a heel qualitative ultrasound (QUS) device. Bone mass distribution was stratified to analyzed and compared with community population.ResultsSchizophrenic patients have lower bone mass while they are young. But aging effect on bone mass cannot be seen. Accelerated bone mass loss during menopausal transition was not observed in the female schizophrenic patients as in the subjects of the community female population.ConclusionSchizophrenic patients have lower bone mass than community population since they are young. Further study to investigate the pathophysiological process is necessary to delay or avoid the lower bone mass in schizophrenia patients.

Socio-demographic and health-related factors associated with cognitive impairment in the elderly in Taiwan

BackgroundCognitive impairment is an age-related condition as the rate of cognitive decline rapidly increases with aging. It is especially important to better understand factors involving in cognitive decline for the countries where the older population is growing rapidly. The aim of this study was to examine the association between socio-demographic and health-related factors and cognitive impairment in the elderly in Taiwan.MethodsWe analysed data from 2119 persons aged 65 years and over who participated in the 2005 National Health Interview Survey. Cognitive impairment was defined as having the score of the Mini Mental State Examination lower than 24. The χ2 test and multiple logistic regression models were used to evaluate the association between cognitive impairment and variables of socio-demography, chronic diseases, geriatric conditions, lifestyle, and dietary factors.ResultsThe prevalence of cognitive impairment was 22.2%. Results of multivariate analysis indicated that low education, being single, low social support, lower lipid level, history of stroke, physical inactivity, non-coffee drinking and poor physical function were associated with a higher risk of cognitive impairment.ConclusionMost of the characteristics in relation to cognitive impairment identified in our analysis are potentially modifiable. These results suggest that improving lifestyle behaviours such as regular exercise and increased social participation could help prevent or decrease the risk of cognitive impairment. Further investigations using longitudinal data are needed to clarify our findings.

Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia

Significance Using network analysis of resting-state functional MRI data, we demonstrate that significant randomization of global network metrics, and greater resilience to targeted attack on network hubs, was replicably demonstrable in Chinese patients with schizophrenia, and was also demonstrated for the first time in their nonpsychotic first-degree relatives. These results support the hypothesis that functional networks are abnormally randomized and resilient in schizophrenia and indicate that network randomization/resilience may be an endophenotype, or marker of familial risk, for schizophrenia. We suggest that the greater randomization of the brain network endophenotype of schizophrenia may confer advantages in terms of greater resilience to pathological attack that may explain the selection and persistence of risk genes for schizophrenia in the general population. Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients’ networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.

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.

Type 2 Diabetes and Antidiabetic Medications in Relation to Dementia Diagnosis

BACKGROUND Type 2 diabetes (T2D) has been shown to increase dementia risk, but few studies evaluated the relationship between antidiabetic treatment and dementia. METHODS We followed up 67,731 participants who were nondemented, nondiabetic, aged 65 or over at baseline from January 2004 to December 2009, to observe the onset of T2D (median follow-up 2.4 years), and to compare the risk of the development of dementia associated with particular types of antidiabetic medication among participants with T2D who had solely one type of antidiabetic agents throughout the follow-up period (median follow-up for participants with T2D 3.1 years). RESULTS The hazard ratio for dementia diagnosis in the new-onset T2D participants compared with the non-T2D participants was 1.56 (95%CI: 1.39-2.18). The relative rate of dementia was 5.31 (95% CI: 1.89-14.96) for participants taking thiazolidinediones (n = 28) and 1.22 (95% CI: 0.78-1.91) for those taking sulfonylureas (n = 796) compared to those taking metformin (n = 1,033). The risk of dementia was higher in ever (n = 841) versus never users (n = 4,579) of thiazolidinediones: 1.44 (95% CI: 1.12-1.86). CONCLUSIONS Diabetes is associated with an increased risk of dementia. The risk effect becomes weaker provided that participants take sulfonylureas or metformin rather than thiazolidinediones for a longer period.

Factors affecting the use of health examinations by the elderly in Taiwan.

This study evaluated the factors associated with use of health examinations by the elderly. Data were obtained from the 2005 National Health Interview Survey (NHIS) in Taiwan for 2,482 individuals aged 65 years or older. The Andersen model was used as the analytic framework, and all variables were categorized into four factors: predisposing, need, health-related behavioral, and enabling factors. The chi(2)-test and a hierarchical multiple logistic regression model were used to examine the association between these variables and the use of health examinations. Nearly half (46.8%) of the elderly had used the service previously. In the final model, those with older age, a spouse, Hakka origin, higher educational level, hypertension, bodily pain, and moderate to high exercise were more likely to use health examinations. On the other hand, older adults who usually used alternative medicine, were missing cognitive test results, were current smokers, and had functional limitations were less likely to use the service. The study results showed that the utilization rate of health examinations was low, suggesting that there is a need to increase its utilization through health education. Furthermore, the factors found in the study may be further used for promoting health examinations.

Reduced neuro-integration from the dorsolateral prefrontal cortex to the whole brain and executive dysfunction in schizophrenia patients and their relatives

Executive dysfunction is one of the core symptoms of schizophrenia. Functional neuro-imaging studies have suggested an association between deficits in activating the dorsolateral prefrontal cortex (DLPFC) and executive dysfunction, but neuro-integration from the DLPFC to the whole brain remains unclear. Studies investigating the neuro-integration from the DLPFC to the whole brain in unaffected but genetically liable family members are scant. In this study, we report DLPFC neuro-integrative deficits correlated with executive dysfunction and family history of schizophrenia using resting-state functional magnetic resonance imaging (fMRI). Using seed regions in DLPFC, we examined resting-state functional connectivity in 25 patients with schizophrenia, 25 unaffected first-degree relatives (UR), and 25 healthy control (HC) persons. Schizophrenia patients and UR have impaired connectivity from DLPFC to its coordinated regions (ANOVA: F=7.316-10.974, p<0.001). These coordinated brain regions are distributed in the bilateral caudate, left middle/inferior frontal gyrus, left precentral gyrus, and right cerebellum. The individual functional connectivity strength between the left DLPFC and its coordinated regions was correlated with individual executive function performance among whole persons. (Pearsons r=0.244-0.366, p=0.035-0.008) Our findings support that distributed neuro-integrative DLPFC deficits reflect a genetic risk for schizophrenia and that these deficits are present, to a lesser degree, in unaffected first-degree relatives. Our findings also support that neuro-integration might correlate with a patients executive function performance.

Panic Disorder and Risk of Stroke: A Population-Based Study

OBJECTIVE An estimate of the risk of stroke among patients with panic disorder was sought. METHOD A retrospective cohort study was conducted using data from the National Health Insurance Research Database in Taiwan. A total of 1725 patients who were newly diagnosed with panic disorder between 2001 and 2007 and had no other psychiatric disorders or history of stroke were included. We then selected our control group by excluding patients with past history of stroke or other mental disorder (n = 388,584). Each patient was tracked from his/her index ambulatory care visit until the end of 2009 to identify whether a stroke was diagnosed during the follow-up periods. The hazard ratios of strokes in panic disorder patients and control group during the observation periods were analyzed with multivariable Cox proportional-hazards models adjusted for age, sex, concurrent medical conditions, and medications. RESULTS In the control group, 19,060 patients (4.9%) had new-onset stroke whereas there were 88 patients (5.1%) in the panic disorder group during the follow-up periods. The risk of stroke was 1.38 times greater for patients with panic disorder than for patients in the control group; (hazard ratio [HR] = 1.38; 95% confidence interval [CI], 1.12-1.71, p = 0.0025). CONCLUSIONS Our findings demonstrated that patients with panic disorder had an increased risk of stroke in Taiwan. Further experimental studies are needed to identify the underlying mechanisms that could lead to early interventions. For panic disorder patients, treatment of their symptoms may be warranted to prevent possible stroke.

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.