Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description.

AIM: Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. MATERIALS AND METHODS: The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. RESULTS: This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. CONCLUSIONS: Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment.

Estudio farmacogenético del tratamiento a largo plazo con antipsicóticos de segunda generación y sus efectos adversos metabólicos (Estudio SLiM): justificación, objetivos, diseño y descripción de la muestra / Pharmacogenetic study of second-generation antipsychotic long-term treatment metabolic side effects (the SLiM Study): rationale, objectives, design and sample description

Objetivo. El aumento de peso es un efecto secundario frecuente e importante de los antipsicóticos de segunda generación (ASG). Además, estos fármacos pueden inducir otros efectos secundarios que están asociados a un aumento de la morbimortalidad cardiovascular, tales como la resistencia a la insulina, la diabetes o el síndrome metabólico. Estudios preliminares indican que las diferencias genéticas interindividuales producen distintos grados de vulnerabilidad a los efectos secundarios inducidos por los ASG. El estudio SLiM (por sus siglas en inglés, Second-generation antipsychotic Long-term treatment Metabolic side effects) tiene como objetivo identificar en pacientes no tratados previamente con ASG (pacientes naive), aquellos factores clínicos, genéticos y ambientales que expliquen las diferencias interindividuales en relación con el aumento de peso y los cambios metabólicos generados tras 6 meses de tratamiento con estos fármacos. Material y métodos. El estudio SLiM es un estudio farmacogenético multicéntrico, observacional, prospectivo, de 6 meses de duración, en el que se ha reclutado una cohorte de 307 pacientes pediátricos y adultos (rango de edad entre 8,8 a 90,1 años) naive a ASG y una cohorte de 150 controles sanos (rango de edad entre 7,8 y 73,2 años) emparejados por edad y sexo. Resultados. En este artículo se presentan la justificación, los objetivos y el diseño del estudio y se ofrece una descripción de la muestra al inicio del estudio. Conclusiones. Los resultados del estudio SLiM permitirán una mejor comprensión de los factores clínicos, ambientales y genéticos implicados en el aumento de peso y los trastornos metabólicos asociados al tratamiento con ASG (AU)

Aim. Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. Materials and methods. The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. Results. This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. Conclusions. Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment (AU)

Pathogenesis of Helicobacter pylori infection.

Helicobacter pylori infection and disease outcome are mediated by a complex interplay between bacterial, host, and environmental factors. Over the past year, our understanding of this complex interplay has been improved by a variety of studies focusing on both host and bacterial factors. These include studies assessing novel virulence factors as well as those most frequently associated with severity of disease outcome including cagA and the cag pathogenicity island, and the vacuolating cytotoxin. Several studies have focused on regulation of virulence factors by environmental factors. In addition, mechanisms by which bacterial virulence factors influence the host response and disease, by inducing epigenetic changes, autophagy and altered oxidative stress have also been elucidated. This review highlights key findings in the pathogenesis of H. pylori infection reported over the past year.

Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study.

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Cognitive impairment is related to oxidative stress and chemokine levels in first psychotic episodes.

INTRODUCTION: This study measures the levels of various markers of oxidative stress and inflammation in blood samples from first-episode psychosis (FEP) patients, and examines the association between these peripheral biomarkers and cognitive performance at 6 months after treatment. METHODS: Twenty-eight FEP patients and 28 healthy controls (matched by age, sex and educational level) had blood samples taken at admission for assessment of total antioxidant status, superoxide dismutase (SOD), total glutathione (GSH), catalase (CAT), glutathione peroxidase, lipid peroxidation, nitrites and the chemokine monocyte chemoattractant protein-1 (MCP-1). A battery of cognitive tests was also applied to the healthy controls and those FEP patients who were in remission at 6 months after the acute episode. RESULTS: FEP patients had significantly lower levels of total antioxidant status, catalase and glutathione peroxidase, compared with the healthy controls. Regression analyses found that MCP-1 levels were negatively associated with learning and memory (verbal and working), nitrite levels were negatively associated with executive function, and glutathione levels were positively associated with executive function. CONCLUSION: Our results suggest an association between certain peripheral markers of oxidative stress and inflammation and specific aspects of cognitive functioning in FEP patients. Further studies on the association between MCP-1 and cognition are warranted.

Psychosis and smoking cessation: difficulties in quitting associated with sex and substance abuse.

No prospective studies of first psychotic episodes have explored sex differences in smoking cessation. The aim of this study was to determine the influence of sex and substance abuse on smoking cessation during an 8-year follow-up of patients after a first psychotic episode. Logistic regression modeling was used to identify factors associated with smoking cessation by sex. To examine for sex variable interactions, the following two methods were used: 1) for other clinical variables, mixed analyses were calculated; and 2) for use of other substances, logistic regression models were performed only in the substance users. At baseline, 79% of men and 84% of women were current smokers. Lower smoking cessation after 8 years was associated with female sex (odds ratio, OR=0.30; 95% confidence intervals, CIs=0.12-0.75) and treatment with typical antipsychotics (OR=0.30, CIs=0.10-0.93). In a logistic regression model of alcohol users, those who used alcohol continuously were less likely to stop smoking (adjusted OR=0.22, CI=0.05-1.0). Among patients who continued using cannabis, female sex was associated with significant lower smoking cessation (adjusted OR=0.03, CI=0.001-0.77). Sex may act as a moderator in smoking cessation after a first psychotic episode. Smoking cessation interventions in these patients should consider sex differences and comorbidity with alcohol and cannabis use.

Oxidative stress by Helicobacter pylori causes apoptosis through mitochondrial pathway in gastric epithelial cells.

Helicobacter pylori is a gram negative bacterium that infects the human stomach of approximately half of the world's population. It produces oxidative stress, and mitochondria are one of the possible targets and the major intracellular source of free radicals. The present study was aimed at determining mitochondrial alterations in H. pylori-infected gastric epithelial cells and its relationship with oxidative stress, one of the recognized causes of apoptotic processes. Cells were treated with a strain of H. pylori for 24 h. Cellular oxidative burst, antioxidant defense analysis, mitochondrial alterations and apoptosis-related processes were measured. Our data provide evidence on how superoxide acts on mitochondria to initiate apoptotic pathways, with these changes occurring in the presence of mitochondrial depolarization and other morphological and functional changes. Treatment of infected cells with Vitamin E prevented increases in intracellular ROS and mitochondrial damage consistent with H. pylori inducing a mitochondrial ROS mediated programmed cell death pathway.