Female Patients Show a Larger Reduction in Suicidal Ideation in Inpatient Addiction Treatment Than Male Patients: Results of a Single-Center Observational Study

Vincent Grote,1,* Tim Wagner,1,2,* David Riedl,1,3 Alexandra Kautzky-Willer,4 Michael J Fischer,1,5,6 Oliver Scheibenbogen,2 Michael Musalek7– 9 1Ludwig Boltzmann Institute for Rehabilitation Research, Ludwig Boltzmann Gesellschaft, Vienna, Austria; 2Anton Proksch Institute, Vienna, Austria; 3University Hospital of Psychiatry II, Medical University of Innsbruck, Innsbruck, Austria; 4Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria; 5Vamed Rehabilitation Center Kitzbühel, Kitzbühel, Austria; 6Clinic for Rehabilitation Medicine, Hannover Medical School MHH, Hannover, Germany; 7Department of General Psychiatry, Sigmund Freud University, Vienna, Austria; 8Institute for Social Aesthetics and Mental Health, Sigmund Freud University, Vienna, Austria; 9Institute for Social Aesthetics and Mental Health, Sigmund Freud University, Berlin, Germany*These authors contributed equally to this workCorrespondence: Vincent Grote; Oliver Scheibenbogen, Email [email protected]; [email protected]: Substance use disorders (SUD) are prevalent disorders worldwide. Among other associated health problems, patients with SUD are at an increased risk of dying of suicide, with females displaying an even higher risk than males. Therefore, the aim of this study was to conduct a gender-sensitive evaluation of changes in suicidal ideation during multimodal inpatient treatment at a hospital facility specialized in treating addiction.Methods: A total of 694 patients (68.2% male) completed routine assessment including suicidal ideation, abstinence confidence, impulsivity, emotion regulation, self-efficacy and autonomy and joy both before (T1) and at the end (T2) of treatment. Mean changes were evaluated with repeated measures MANOVAs.Results: Before treatment, a total of n=127 (18.3%) of the respondents reported suicidal ideation, which was reduced to n=72 (10.4%) by the end of treatment. Among female patients, the change in reported suicidal ideation compared from T1 to T2 (21.7% vs 7.7%) was significantly higher than among male patients (T1: 16.7%%, T2: 11.6%; p=0.040). Generally, females reported worse symptoms scores and slightly higher numbers of suicidal thoughts at baseline (effect sizes ranging from η²=.008 – 0.044). While both genders significantly profited from the treatment, female patients generally showed larger improvements than male.Discussion: Our study underscores the beneficial effect of addiction-specialized inpatient treatment on suicidal ideation. Additionally, we found a substantial gender effect: while female patients generally were more distressed before treatment, they also reported higher symptom reduction during the treatment. This result highlights the need to perform more gender-sensitive research and develop more gender-sensitive treatment programs.Keywords: addiction, inpatient therapy, alcohol, drugs, gender medicin

Evolution of cooperation driven by zealots

Recent experimental results with humans involved in social dilemma games suggest that cooperation may be a contagious phenomenon and that the selection pressure operating on evolutionary dynamics (i.e., mimicry) is relatively weak. I propose an evolutionary dynamics model that links these experimental findings and evolution of cooperation. By assuming a small fraction of (imperfect) zealous cooperators, I show that a large fraction of cooperation emerges in evolutionary dynamics of social dilemma games. Even if defection is more lucrative than cooperation for most individuals, they often mimic cooperation of fellows unless the selection pressure is very strong. Then, zealous cooperators can transform the population to be even fully cooperative under standard evolutionary dynamics.Comment: 5 figure

Transgenic Rescue of the LARGEmyd Mouse: A LARGE Therapeutic Window?

LARGE is a glycosyltransferase involved in glycosylation of α-dystroglycan (α-DG). Absence of this protein in the LARGEmyd mouse results in α-DG hypoglycosylation, and is associated with central nervous system abnormalities and progressive muscular dystrophy. Up-regulation of LARGE has previously been proposed as a therapy for the secondary dystroglycanopathies: overexpression in cells compensates for defects in multiple dystroglycanopathy genes. Counterintuitively, LARGE overexpression in an FKRP-deficient mouse exacerbates pathology, suggesting that modulation of α-DG glycosylation requires further investigation. Here we demonstrate that transgenic expression of human LARGE (LARGE-LV5) in the LARGEmyd mouse restores α-DG glycosylation (with marked hyperglycosylation in muscle) and that this corrects both the muscle pathology and brain architecture. By quantitative analyses of LARGE transcripts we also here show that levels of transgenic and endogenous LARGE in the brains of transgenic animals are comparable, but that the transgene is markedly overexpressed in heart and particularly skeletal muscle (20–100 fold over endogenous). Our data suggest LARGE overexpression may only be deleterious under a forced regenerative context, such as that resulting from a reduction in FKRP: in the absence of such a defect we show that systemic expression of LARGE can indeed act therapeutically, and that even dramatic LARGE overexpression is well-tolerated in heart and skeletal muscle. Moreover, correction of LARGEmyd brain pathology with only moderate, near-physiological LARGE expression suggests a generous therapeutic window

Inflammation, insulin resistance, and diabetes-mendelian randomization using CRP haplotypes points upstream

Background Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. Methods and Findings We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p=0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p=0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p=0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations. Conclusions Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy

The struggle for existence in the world market ecosystem

The global trade system can be viewed as a dynamic ecosystem in which exporters struggle for resources: the markets in which they export. We can think that the aim of an exporter is to gain the entirety of a market share (say, car imports from the United States). This is similar to the objective of an organism in its attempt to monopolize a given subset of resources in an ecosystem. In this paper, we adopt a multilayer network approach to describe this struggle. We use longitudinal, multiplex data on trade relations, spanning several decades. We connect two countries with a directed link if the source country's appearance in a market correlates with the target country's disappearing, where a market is defined as a country-product combination in a given decade. Each market is a layer in the network. We show that, by analyzing the countries' network roles in each layer, we are able to classify them as out-competing, transitioning or displaced. This classification is a meaningful one: when testing the future export patterns of these countries, we show that out-competing countries have distinctly stronger growth rates than the other two classes

Organic Agriculture

Consumers are increasingly aware of the health- and safety-related implications of the food which they can buy in the market. At the same time, households have become more aware of their environmental responsibilities. Regarding the production of food, a crucial and multifunctional role is played by agriculture. The way vegetables, fruits, and other crops are grown and how livestock is raised has an impact on the environment and landscape. Operations performed by farmers, such as water management, can be dangerous for the soil and the whole ecosystem. Consequently, there is a search for natural ways of sustaining the impact of agriculture on the environment. In this context, one of the most popular ideas is organic agriculture. In the literature on the subject, there are many concepts that some authors consider to be synonymous even as others argue that these terms are not interchangeable. There is, for example, "organic agriculture," "alternative agriculture," "sustainable agriculture," "ecological agriculture," "biological agriculture," "niche farming," "community-supported agriculture," and "integrated pest management." Very often, techniques and products related to organic agriculture are described by marketing experts with the use of abbreviations such as "bio" and "eco." Products with such markings and labels are increasingly popular in stores that often give them separate shelves for their sale. Despite the higher price compared to conventional products, they are increasingly sought by consumers. The entry examines the various impacts of organic agriculture with a view to these trends

Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans.

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome-wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European-Americans (EA; 2927 cases) and 3132 African-Americans (AA: 1315 cases) participating in the family-based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome-wide significant (GWS; P < 5E-08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion-deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans-ancestral meta-analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward-related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non-European samples with distinct patterns of substance use may lead to the identification of novel ancestry-specific genetic markers of risk

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function