Adjunctive aripiprazole treatment reversed hyperprolactinemia in both sexes, resulting in reinstatement of menstruation in female patients, with no significant effects on psychopathology and extrapyramidal symptoms. Aripiprazole has higher affinity to dopamine D(2) receptors than haloperidol, which is the likely cause of this observation.

This study examined effects of cigarette smoking on mortality risk in 1213 persons aged 19-69 years with schizophrenia-related psychotic disorders admitted to State of Maryland Hospitals between 1994 and 2000. Inpatient medical records from 7 hospitals were reviewed to obtain demographic information, diagnosis, medication use, as well as smoking and other substance use. Social Security Death Index data were used to identify deaths in the study group between 1994 and 2004. Death records were reviewed to obtain manner of death and underlying disorders. Of the 1213, 55% were smokers and 71% abused substances. There was an age × smoking interaction (χ(2) = 14.6, df = 1, P = .0001) for mortality, with estimated hazard ratios (HRs) for smokers vs nonsmokers of 2.1 among 35- to 54-year olds and HR of 0.7 among those aged 55-69 years. Five- and 10-year mortality rates for smokers aged 35-54 years were 7.0% and 14.2%, compared with 3.3% and 10.0% for nonsmokers, respectively (χ(2) = 5.53, df = 1, P = .019). Cardiac causes were identified in 43% of deaths in smokers but only 19% of deaths in nonsmokers (P < .006). For those aged 35-54 years, the odds of cardiac related death was increased by 12 fold in smokers relative to nonsmokers (HR = 12.4, χ(2) = 12.0, df = 1, P = .0005). Among people aged 35-54 years, those smoking greater than one pack daily have a significantly increased total mortality risk (HR = 2.7) vs nonsmokers. Cigarette smoking, particularly in people aged 35-54 years, contributes to an increased risk of death. Greater smoking severity significantly increases this risk. Smoking cessation in people with schizophrenia deserves significant attention.

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We investigate all the four-body graviton interaction processes: gX → γX, gX → gX, and gg → gg with X as an elementary particle of spin less than two in the context of linearized gravity except the spin-3/2 case. We show explicitly that gravitational gauge invariance and Lorentz invariance cause every four-body graviton scattering amplitude to be factorized. We explore the implications of this factorization property by investigating polarization effects through the covariant density matrix formalism in each four-body graviton scattering process. PACS number(s) : 04.60.+n, 12.25.+e, 13.88.+e

ABSTRACT:Genetic variants of three human organic cation transporter genes (hOCTs) were extensively explored in a Korean population. The functional changes of hOCT2 variants were evaluated in vitro, and those genetic polymorphisms of hOCTs were compared among different ethnic populations. From direct DNA sequencing, 7 of 13 coding variants were nonsynonymous single-nucleotide polymorphisms (SNPs), including four variants from hOCT1 (F160L, P283L, P341L, and M408V) and three from hOCT2 (T199I, T201M, and A270S), whereas 6 were synonymous SNPs. The linkage disequilibrium analysis presented for three independent LD blocks for each hOCT gene showed no significant linkage among all three hOCT genes. The transporter activities of MDCK cells that overexpress the hOCT2-T199I, -T201M, and -A270S variants showed significantly decreased uptake of showed a 2-to 5-fold increase in K m values and a 10-to 20-fold decrease in V max values. The allele frequencies of the five functional variants hOCT1-P283L, -P341L, and hOCT2-T199I, -T201M, and -A270S were 1.3, 17, 0.7, 0.7, and 11%, respectively, in a Korean population; the frequency distributions of these variants were not significantly different from those of Chinese and Vietnamese populations. These findings suggest that genetic variants of hOCTs are not linked among three genes in a Korean population, and several of the hOCT genetic variants cause decreased transport activity in vitro compared with the wild type, although the clinical relevance of these variants remains to be evaluated.The human organic cation transporters hOCT1, hOCT2, and hOCT3 mediate electrogenic transport of small organic cations with different molecular structures, independent of sodium gradient (Koepsell, 1999). These organic cation substrates include clinically important therapeutics (e.g., metformin, procainamide, and cimetidine), endogenous compounds (e.g., dopamine and norepinephrine), as well as toxic substances [e.g., tetraethylammonium bromide (TEA), HPP ϩ , and methyl-4-phenylpyridinium acetate (MPP ϩ )] (Gorboulev et al., 1997;Zhang et al., 1997;Kang et al., 2006). Although these transporters show extensive overlaps in their substrate specificities, they exhibit distinct differences in tissue distribution; hOCT1 is primarily found in the sinusoidal membrane of hepatocytes and, to a lesser extent, in intestinal epithelial cells, whereas hOCT2 is mainly expressed in the basolateral membrane of kidney proximal tubules, and hOCT3 shows a widespread tissue distribution that includes the brain, heart, and liver. Based on their properties and tissue distributions, hOCT1, hOCT2, and hOCT3 are thought to play important roles in the excretion and distribution of organic cations in the liver, kidney, and brain (Jonker and Schinkel, 2004).Knockout mouse models have been generated for the Oct1, Oct2, and Oct3 genes to elucidate the in vivo function of the OCT transporters. Oct1-, Oct2-, and Oct3-deficient mice are viable and display no obvious phenotypic abnormalities (Jonker et al., 2001Zwart et al., 2001...

The aim of this study is to examine the effects of treatment with varenicline, a partial agonist at the a4b2 and full agonist at the a7 nicotine acetylcholine receptor, on cognitive impairments in people with schizophrenia. In all, 120 clinically stable people with schizophrenia participated in randomized, double-blind, placebo-controlled 8-week trial. Antipsychotic and concomitant medication doses remained fixed throughout the study. Varenicline was titrated up to 1 mg twice daily for weeks 2-8. Neuropsychological, clinical, and safety assessments were administered at baseline and weeks 1, 2, 4, and 8. In the primary analyses of neurocognitive differences at week 8, no varenicline-placebo differences were significant. In secondary longitudinal analyses, varenicline improved compared with placebo on the Digital Symbol Substitution Test (p ¼ 0.013) and the Wisconsin Card Sorting Test non-perseverative errors (p ¼ 0.043). Some treatment effects were different between smokers and non-smokers. In smokers, Continuous Performance Test hit reaction time (p ¼ 0.008) and Stroop Interference (p ¼ 0.004) were reduced for varenicline compared with placebo, while there were no treatment differences in non-smokers. No significant treatment main effects or interactions were noted for total scores on the Positive and Negative Syndrome Scale or the Scale for the Assessment for Negative Symptoms. Our findings suggest beneficial effects of adjunctive varenicline treatment with antipsychotics for some cognitive impairments in people with schizophrenia. In some cases, effects of treatment varied between smokers and non-smokers. Further study is required to assess the functional significance of these changes.

Background Cardiovascular disease (CVD) mortality in schizophrenia is more frequent than in the general population. Whether second generation antipsychotics (SGAs) increase risk of CVD morbidity and mortality has yet to be determined. Methods Using an administrative database, we identified schizophrenia patients, treated in Maryland, who started clozapine (n=1084) or never treated with clozapine (initiated on risperidone)(n=602) between 1994 and 2000. Deaths between 1994 and 2004 were identified by the Social Security Death Index and death records were obtained. Results During the 6–10 year followup period there were 136 deaths of which 43 were CVD. CVD mortality in patients < 55 years old at medication start was approximately 1.1% (cloz: 1.1%, risp: 1.0%) in both groups at five years, and 2.7% (clozapine) and 2.8% (risperidone) at ten years (χ2=0.12, df=1, p=0.73). Patients started ≥ 55 years had CVD mortality of 8.5% (clozapine) and 3.6% (risperidone) at five years and 16.0%(clozapine) and 5.7% (risperidone) at ten years (χ2 =2.13, df=1, p=0.144). In a Cox regression model, patients with age ≥55 years were at greater risk of mortality than younger patients (HR=4.6, p<0.001); whites were at greater risk than non-whites (HR=2.1, p=0.046); however, SGA treatment (HR=1.2, 95% CI 0.6 to 2.4, p=0.61) and sex (HR=0.9, p=0.69), were not statistically significant predictors of CVD; nor was there a significant age x clozapine interaction (χ2=1.52, df=1, p=0.22). Age-, race-, and gender adjusted Standardized Mortality Ratios (SMR) were significantly elevated (clozapine 4.70, 95%CI=3.19–6.67; risperidone 2.88, 95%CI=1.38–5.30) compared to year 2000 rates for the Maryland general population but did not differ by antipsychotic group (Π2=1.42, df=1, p=0.23). Conclusions The risk of CVD mortality in schizophrenia does not differ between clozapine and risperidone in adults despite known differences in risk profiles for weight gain and metabolic side effects. However, we cannot rule out an increased risk of CV mortality among those starting treatment at age ≥ 55 years.

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