Polygenic risk for schizophrenia and neurocognitive performance in patients with schizophrenia.

Both neurocognitive deficits and schizophrenia are highly heritable. Genetic overlap between neurocognitive deficits and schizophrenia has been observed in both the general population and in the clinical samples. This study aimed to examine if the polygenic architecture of susceptibility to schizophrenia modified neurocognitive performance in schizophrenia patients. Schizophrenia polygenic risk scores (PRSs) were first derived from the Psychiatric Genomics Consortium (PGC) on schizophrenia, and then the scores were calculated in our independent sample of 1130 schizophrenia trios, who had PsychChip data and were part of the Schizophrenia Families from Taiwan project. Pseudocontrols generated from the nontransmitted parental alleles of the parents in these trios were compared with alleles in schizophrenia patients in assessing the replicability of PGC-derived susceptibility variants. Schizophrenia PRS at the P-value threshold (PT) of 0.1 explained 0.2% in the variance of disease status in this Han-Taiwanese samples, and the score itself had a P-value 0.05 for the association test with the disorder. Each patient underwent neurocognitive evaluation on sustained attention using the continuous performance test and executive function using the Wisconsin Card Sorting Test. We applied a structural equation model to construct the neurocognitive latent variable estimated from multiple measured indices in these 2 tests, and then tested the association between the PRS and the neurocognitive latent variable. Higher schizophrenia PRS generated at the PT of 0.1 was significantly associated with poorer neurocognitive performance with explained variance 0.5%. Our findings indicated that schizophrenia susceptibility variants modify the neurocognitive performance in schizophrenia patients.

Transformation of excess mortality in people with schizophrenia and bipolar disorder in Taiwan.

BACKGROUND: Given the concerns regarding the adverse health outcomes associated with weight gain and metabolic syndrome in relation to use of second-generation antipsychotics (SGAs), we aimed in this study to explore whether the increase in the use of SGAs would have any impacts on the trend of excess mortality in people with schizophrenia and bipolar disorder (BPD). METHOD: Two nationwide samples of individuals with schizophrenia and BPD were identified in Taiwan's National Health Insurance Research Database in 2003 and in 2008, respectively. Age- and gender-standardized mortality ratios (SMRs) were calculated for each of the 3-year observation periods. The SMRs were compared between the calendar year cohorts, by disease group, and by causes of death. RESULTS: The mortality gap for people with schizophrenia decreased slightly, revealing an SMR of 3.40 (95% CI 3.30-3.50) for the 2003 cohort and 3.14 (3.06-3.23) for the 2008 cohort. The mortality gap for BPD individuals remained relatively stable with only those aged 15-44 years having an SMR rising significantly from 7.04 (6.38-7.76) to 9.10 (8.44-9.79). Additionally, in this group of BPD patients aged 15-44 years, the natural-cause-SMR increased from 5.65 (4.93-6.44) to 7.16 (6.46-7.91). CONCLUSIONS: Compared with the general population, the gap in the excess mortality for people with schizophrenia reduced slightly. However, the over 200% difference between the cohorts in the excess mortality for BPD individuals aged 15-44 years could be a warning sign. Future research to further examine the related factors underlying those changes is warranted.

Another look at differences in the susceptibility of Escherichia coli and Klebsiella pneumoniae to cephalothin and cefazolin.

The significance of in vitro susceptibility tests on Enterobacteriaceae to cephalothin and cefazolin has not been exactly defined in the guidelines of the National Committee for Clinical Laboratory Standards. In the hope of clarifying this confusion, we provide additional information from an ancillary study of the Taiwan Surveillance of Antimicrobial Resistance 1998 (TSAR I). There were 505 Escherichia coli and 227 Klebsiella pneumoniae isolates susceptible to cephalothin, reported by 42 participating hospitals. The susceptibility of these isolates were re-tested at the Microbial Infections Reference Laboratory using cefazolin, with the result that 72% of the 252 cephalothin-resistant E. coli isolates and 24% of the 41 cephalothin-resistant K. pneumoniae isolates were found to be susceptible to cefazolin. We further surveyed the availability of cephalothin and cefazolin in Pharmacy Departments; all of the TSAR I hospitals had cefazolin available in their pharmacies. The resistance rate of E. coli was significantly lower for 12 hospitals that had cefazolin in both pharmacy and laboratory compared with 11 hospitals that had cefazolin available in pharmacy but cephalothin in laboratory. In addition, for all the hospitals that had cephalothin available for clinical use, the resistance rate was twice as low in two hospitals reporting cefazolin susceptibility as in the seven hospitals reporting cephalothin susceptibility. Our findings suggest that inappropriate selection of cephalothin and cefazolin for susceptibility testing contribute to inaccurate indications of in vivo activity for first generation cephalosporins in the treatment of E. coli infections.

Surveillance of antibiotic resistance in Taiwan, 1998.

For the first national surveillance of antibiotic resistance in Taiwan, we collected in 1998 from 22 hospitals (6 medical centers, 15 regional hospitals, and 1 local hospital) 3,211 isolates in all parts of the country. Besides 50 random successive isolates from inpatients, each hospital was requested to collect 25 isolates each from positive blood cultures, hospital-acquired infections, outpatients and the pediatric department. We re-speciated all the submitted specimens and determined their antibiotic susceptibility patterns. The most common isolates were Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae), Staphylococcus aureus, and Pseudomonas aeruginosa. Among hospital-acquired infections, Acinetobacter spp. were among those which accounted for over 10% of the isolates. The oxacillin resistance of S. aureus was 82% in isolates from hospital-acquired infections, and 40% from outpatients. Among Enterococcus spp., 85% were either E. faecalis or E. faecium. They were 14% resistant to vancomycin. Among gram-negative bacteria, K. pneumoniae and Acinetobacter baumanii were hospital-acquired isolates that were most clearly more resistant than community acquired isolates. This difference was less apparent in the case of Enterobacter cloacae, Serratia marcescens, and P. aeruginosa. These bacteria were generally more resistant from all sources. Fifty-one percent of Salmonella were resistant to ampicillin; however, these were all sensitive to ciprofloxacin. Isolates from the East were least resistant. Plotting the disc zone diameters of antibiotics within the susceptible range, we identified subpopulations with smaller diameters in the case of vancomycin against S. aureus, ciprofloxacin against E. coli, and ciprofloxacin against Salmonella spp. These findings represent one of the purposes of this surveillance as they may portend developing resistances which bear careful watching in the future.

Concordance of positive and negative symptoms in coaffected sib-pairs with schizophrenia.

Positive and negative symptom (NGS) dimensions were examined for their concordance in 46 coaffected schizophrenic sib-pairs. Results showed that the symptom dimensions of negative symptoms (NGS), delusion-hallucination (DHS), and thought disorganization (TDS) could be formulated. Discrete genetic endowment of these three symptom dimensions was not found as shown by the low concordance in sib pair analysis (kappa = 0.20-0.30). Thirty-seven pairs (80.4%) and 21 pairs (45.7%) had liability, defined by the presence of NGS in any one member of the coaffected sib-pairs, of NGS of "any degree", and of "severe degree" in 46 sib-pairs, respectively. Both groups had high prevalence (59.1-81.0%) of positive symptoms. Another 9 (19.6%) and 25 (54.3%) pairs had no liability of NGS of "any degree" or of "severe degree" out of 46 sib-pairs, respectively. These two groups had high concordance (kappa = 0.45-1.00) of TDS or DHS between coaffected sib-pairs. Based on the results, it is hypothesized that schizophrenia, as defined by DSM-III-R, may consist of two subtypes: one has liability of NGS and a high prevalence of positive symptoms, while the other has only positive symptoms.

Major depressive disorder in Taiwan defined by the Chinese diagnostic Interview Schedule.

The lifetime prevalence rate of major depressive disorder (MDD), as defined by the Chinese Diagnostic Interview Schedule, is 1.14% in Taiwan. This is significantly lower than the lifetime prevalence rates reported in Western studies and similar to other studies in the Chinese population using similar methods for assessing cases of MDD. Epidemiological data from 136 MDD cases were analyzed to provide possible explanations for this difference in lifetime prevalence rates. The low rate of broken families in Chinese culture, low comorbidity rate, and older age of onset of MDD may suggest a reality of low lifetime prevalence rates of MDD in Taiwan.

The role of socioeconomic status and serum fatty acids in the relationship between intake of animal foods and cardiovascular risk factors.

Little is known regarding the relationship of serum fatty acids to cardiovascular risk factors in Nigerian populations. Civil servants with higher socioeconomic status (SES) in Nigeria appear to be in cultural transition toward a more Westernized lifestyle. For this study the food intakes of 397 civil servants were estimated from two 24-h recalls. Fatty acids in serum total lipids were measured in both absolute weight concentration and percentage composition. Daily meat intake was 43.5 g, and fish intake was 70.5 g. The intakes of meat, eggs, and milk were higher in high SES Nigerians than in low SES Nigerians. The concentration of total fatty acids (TFA, the sum of 12 serum fatty acids) was also higher in high SES men and women, as compared with low SES men and women (2064, 2060, 1831, and 1776 mg/L, respectively). There were significant direct associations between meat intake and serum level of arachidonic acid, and between fish intake and serum levels of eicosapentaenoic acid and docosahexaenoic acid. TFA was positively associated with cholesterol, low-density-lipoprotein cholesterol (LDLc), and triglycerides across gender and SES groups after adjustment for body mass index, fasting insulin level, and age. Nigerian women were compared with two groups of American women. We concluded that fatty acids in absolute weight concentration reflected the amount of fat intake. The level of TFA was directly related to cardiovascular risk factors in Nigerians. Follow-up of such populations in cultural transition can facilitate the understanding of the true roles of animal food intake in the early evolution of atherosclerosis.

Excess mortality of psychiatric inpatients in Taiwan.

The 6-year mortality rate of a nation-wide cohort of Taiwanese psychiatric inpatients admitted during the 1-year period from 1987 to 1988 was examined via record linkage. The psychiatric care system in Taiwan is mainly hospital-based. Of the 13,385 patients studied (9309 men and 4076 women), 2039 (1720 men and 319 women) had died by the end of 1993. The standardized mortality ratio (SMR) in this sample (3.10 for men and 4.83 for women) was as high as those reported in western industrialized countries during the pre-deinstitutionalization era. We also examined the relationship between the excess mortality of patients and age, sex, causes of death, diagnostic categories, and length of hospital stay. In general, the SMR was greatest for the youngest age group, women, unnatural deaths, substance use disorders, and in the first year after admission. Although the main cause for the excess mortality was unnatural deaths, there was also an excess mortality due to natural causes across all diagnostic categories. Several recommendations for the improvement of psychiatric care in Taiwan are made on the basis of these findings.

Month of birth and schizophrenia in Taiwan: effect of gender, family history and age at onset.

Schizophrenic patients have been shown to have a moderate excess of winter births in the areas where seasonal variations in weather are large. In this report, we examined the seasonality of schizophrenic births in Taiwan, which has a subtropical climate. Using nationwide hospitalization data (2429 male and 1320 female schizophrenic patients), we applied the life table method to compare the risk of schizophrenia among 12 cohorts of month-of-birth for males and females, respectively. Differences among the risks of the 12 cohorts were tested using the logrank test. The samples were further stratified by family history and age at onset. There was a significant association between the risk of being admitted as a schizophrenic and month of birth for both males and females. The cohorts born in November and January had the highest risks. After stratification, the association was significant only for non-familial, male, and early onset schizophrenic patients. The results indicate that seasonally varying factors might increase the risk of schizophrenia, especially in those without a family history of the disease. Men are more vulnerable to such factors than women, and the schizophrenics resulting from such insults tend to be early onset.

Negative symptoms at discharge and outcome in schizophrenia.

BACKGROUND: The clinical significance in schizophrenia of positive and negative symptoms at discharge was assessed. METHOD: Of schizophrenic patients fulfilling DSM-III criteria, 113 were recruited for this study. Personal, social and psychopathological data were collected and all cases were followed up at one and two years after discharge. RESULTS: The presence of positive symptoms (64 cases), without concomitant negative symptoms, did not predict the follow-up social function and positive symptom score. Conversely, the presence of negative symptoms (31 cases) predicted worse social functioning (P < 0.05 to P < 0.005) and higher positive symptom scores (P < 0.01) at follow-up using MANOVA: Eighteen cases (15.9%) had neither positive nor negative symptoms and had the best clinical outcome. CONCLUSIONS: Negative, but not positive, symptoms assessed at discharge are an important predictor of poor outcome. In addition, negative symptoms may themselves expose a biological vulnerability to the presence of positive symptoms.

Factors associated with hypertension in Nigerian civil servants.

BACKGROUND: Study of hypertension in segments of West African populations in transition toward Westernization may lead to better understanding of the high risk for hypertension among Westernized blacks. METHODS: Five hundred fifty-nine urban civil servants, ages 25-54, were recruited from six ministries of Bendel State, Nigeria. Blood pressure, physical measurements, urinary protein and glucose, fasting blood glucose, and demographic data were collected at the workplace. Subjects were classified as senior staff (professionals or administrators) or junior staff (non-administrators). RESULTS: Among 172 male senior staff, the age-adjusted rate of hypertension (diastolic blood pressure > or = 90 mm Hg, systolic blood pressure > or = 140 mm Hg, or on an antihypertensive medication) was 43% and occurrence rose dramatically from 21 to 63% across age groups 25-34 to 45-54, respectively. Among 266 male junior staff, the age-adjusted rate of hypertension was 23%, and occurrence did not rise with age. Logistic regression showed that body mass index (kg/m2), age, alcohol drinking, and being senior staff were all independently related to hypertension in men. On the other hand, the age-adjusted rate of hypertension in 121 women was 20% and was significantly related only to body mass index. CONCLUSION: Male urban civil servants appeared to have a risk for hypertension similar to that of U.S. black males. Age, body mass index, alcohol drinking, and other unidentified factors related to higher socioeconomic status were strong determinants of hypertension in this population.

A typology of alcoholism in Taiwan aborigines: a study on evolving process of community cases.

Thirty-one habitual drinkers with a personal, familial, social complication were screened from a Taiwan aborigine community. Each was given an in-depth descriptive semistructured interview. The interview, recorded with audiotape, contained 4 aspects: (1) personal developmental history; (2) family structure and interaction; (3) developmental process and current state of drinking behavior, and (4) attitude toward drinking behavior. Based on the evolving process and current state of drinking behavior, three process patterns of alcoholism were defined: (1) social developmental type (67.7%); (2) deviant behavioral type (9.7%), and (3) special constitutional type (22.6%).

Factors related to blood pressure among urban Nigerian workers.

This cross-sectional study of urban, Nigerian civil servants found that age, body mass index, alcohol drinking and high socioeconomic status were all positively and independently related to blood pressure among 438 males. Among 121 females, only body mass index was significantly related to blood pressure.

Blood pressure and other cardiovascular disease risk factors in black adults with sickle cell trait or glucose-6-phosphate dehydrogenase deficiency.

In this study, we examined the relationship of two common genetic markers in black populations, sickle cell trait and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency, to cardiovascular risk factors. The subjects were Nigerian civil servants in Benin City, Nigeria. We measured blood pressure, height, weight, sickle cell hemoglobin, G-6-PD, proteinuria, microalbuminuria and fasting serum cholesterol, high-density lipoprotein cholesterol (HDL), triglycerides, apoprotein (APO) AI, and APO B. Data were collected on age, alcohol consumption, cigarette smoking, job status, and years lived in an urban area. There were 257 males (3 SS hemoglobin, 73 AS, 181 AA) and 69 females (23 AS, 46 AA). In comparing cardiovascular risk factors, males differed only in percent of smokers (31.5 in AS vs. 17.8 in AA, P less than 0.01). Among females, only high-density lipoprotein (HDL) cholesterol differed (61.5 mg/dl in AS vs. 52.4 in AA, P less than 0.01). We hypothesize that females with sickle cell trait are more likely to use oral contraceptives than nontrait females. If so, the high-estrogen oral contraceptives available in Nigeria could elevate HDL. G-6-PD deficiency status among males (52 deficient, 207 nondeficient) and females (1 deficient, 5 carriers, 65 nondeficient) was not related to any of the cardiovascular risk factors. We conclude that sickle cell hemoglobin trait and G-6-PD deficiency are not useful genetic markers for risk factors for cardiovascular disease.

An improved preparation of phosphatidylglycerophosphate.

Phosphatidylglycerophosphate is not normally accumulated in the reaction mixture. It was found that octyl-beta-D-glucopyranoside greatly stimulated the synthesis and inhibited the degradation of phosphatidylglycerophosphate. The phenomenon could be used for the preparation of phosphatidylglycerophosphate from CDPdiacylglycerol and the sn-glycero-3-phosphate with the crude membrane enzyme preparation. The optimal concentration of octyl-beta-D-glucopyranoside to be used for such a purpose was 24.5 mM.

Phosphatidyl glycerolphosphate serves as glycerolphosphate donor in polymer synthesis.

Phosphatidyl glycerolphosphate was found to serve as the glycerolphosphate donor for polymer synthesis. When CDP-diglyceride and radiolabeled glycerolphosphate were incubated with the membrane enzyme prepared from Streptococcus sanguis, active syntheses of radiolabeled lipids and polymers were observed. The synthesis of polymer was not inhibited by low concentration of unlabeled phosphatidylglycerol. When [3H, 32P]glycerolphosphate was used, the polymer synthesized contained both 3H and 32P. The lipids formed were characterized as phosphatidylglycerol and phosphatidyl glycerolphosphate. The polymers formed from the latter were characterized as lipoteichoic acid like compounds by sodium dodecylsulfate-polyacrylamide gel electrophoresis.