Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1

Abstract: Impulsivity describes the tendency to act prematurely without appropriate foresight and is symptomatic of a number of neuropsychiatric disorders. Although a number of genes for impulsivity have been identified, no study to date has carried out an unbiased, genome-wide approach to identify genetic markers associated with impulsivity in experimental animals. Herein we report a linkage study of a six-generational pedigree of adult rats phenotyped for one dimension of impulsivity, namely premature responding on the five-choice serial reaction time task, combined with genome wide sequencing and transcriptome analysis to identify candidate genes associated with the expression of the impulsivity trait. Premature responding was found to be heritable (h2 = 13–16%), with significant linkage (LOD 5.2) identified on chromosome 1. Fine mapping of this locus identified a number of polymorphic candidate genes, however only one, beta haemoglobin, was differentially expressed in both the founder strain and F6 generation. These findings provide novel insights into the genetic substrates and putative neurobiological mechanisms of impulsivity with broader translational relevance for impulsivity-related disorders in humans

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p<0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Learning not to be impulsive: disruption by experience of alcohol withdrawal

RATIONALE There is extensive evidence that alcoholism and impulsivity are related, but the direction of causality is unclear. OBJECTIVES The aim of the present investigation was to study the effects of chronic ethanol treatment and withdrawal in measures of attention and impulse control in the five-choice serial reaction time task (5CSRTT) in mice. MATERIALS AND METHODS C57BL/6J mice were trained in the 5CSRTT and then tested in a variable inter-trial interval (vITI) session, which promotes the emergence of premature responses, a measure of poor inhibitory control. Following chronic ethanol treatment, mice were tested in additional vITI sessions-in experiment 1, at 1, 7 and 14 days post-withdrawal, and in experiment 2, at 14, 28, 42 and 56 days post-withdrawal. RESULTS Control animals showed a reduction in premature responding with experience of the vITI schedule. Compared to controls, previous ethanol treatment did not affect attention or impulsivity on first experience of the vITI procedure. Ethanol-treated animals showed sustained increased premature responding over sessions. This effect of ethanol treatment was not apparent in experiment 2, in which first exposure to the vITI schedule was delayed for 2 weeks following ethanol treatment. CONCLUSIONS Chronic ethanol treatment impaired the ability to learn to modify behaviour in order to gain access to reinforcement more frequently. This effect was related to the time since withdrawal

Repeated ethanol exposure during early and late adolescence: double dissociation of effects on waiting and choice impulsivity

BACKGROUND: A strong association exists between impulsivity and binge drinking, and between adolescent alcohol exposure and alcohol abuse in humans. To understand the extent to which early-life alcohol exposure contributes to increased impulsivity, we developed an animal model of binge drinking using 2 strains of mice, C57BL/6J (B6) and DBA2/J (D2), that differ in both motor impulsivity and alcohol drinking. METHODS: Mice were treated with 2 g/kg ethanol (EtOH) during their early (intermittent ethanol exposure [IEE]_Early; postnatal day [PND]30 to 45) or late (IEE_Late; PND45 to 60) adolescence or with saline (control group [CON]) throughout the adolescence period. To determine the consequences IEE on waiting impulsivity and attentional function, the number of premature responses and omissions, respectively, were evaluated in adulthood using the 5-choice serial reaction time task (5-CSRTT). To examine the effects of IEE on choice impulsivity, risky decision making was assessed in adulthood using a mouse version of the Iowa Gambling Task (mIGT). Additionally, the acute effects of EtOH in adulthood on waiting impulsivity and choice preference were investigated. RESULTS: We provide experimental evidence that IEE during late, but not early, adolescence disrupts waiting impulsivity and attentional abilities in the 5-CSRTT. In contrast, IEE during early, but not late, adolescence altered risky decision making in the mIGT. D2 mice consistently showed lower premature responding than B6 mice in both the mIGT and the 5-CSRTT, but greater risky decision making on the mIGT. IEE and CON mice showed similar responsiveness to the acute EtOH effects on premature responding, but increased risky choices only in B6_IEE_Early mice. CONCLUSIONS: Our observations suggest a direct effect of IEE during adolescence on waiting and choice impulsivity and attention later in life

Alpha-synuclein deletion decreases motor impulsivity but does not affect risky decision making in a mouse Gambling Task

Rationale: There is evidence to support the role of alphasynuclein in motor impulsivity, but the extrapolation of this finding to other types of impulsivity remains to be elucidated. Objective: This study aims to investigate the role of alphasynuclein in choice impulsivity/risky decision-making bymeans of a mouse version of the Iowa Gambling Task (mIGT). Methods: Two strains of mice that differ in the expression of the alpha-synuclein gene, the C57BL/6JOlaHsd (HA) and C57BL/6J (CR), were tested in the mIGT. HA mice differ from their CR ancestors in possessing a chromosomal deletion resulting in the loss of two genes: snca, encoding alphasynuclein and mmrn1, encoding multimerin-1. Mice were trained in the mIGT until a stable pattern of responding was achieved and then the acute effects of ethanol and cocaine in choice preference were investigated. Results: No differences between the strains were evident in risky decision-making in any of the experiments, but HA mice showed consistently reduced levels of premature responding in comparison with CR mice, confirming the reduced motor impulsivity found in a previous study. Ethanol did not modify the percentage of advantageous choices in either strain, while cocaine increased the risky choice behaviour by increasing the percentage of disadvantageous choices in both strains. Conclusions: We provide further evidence for the involvement of alpha-synuclein in motor impulsivity and suggest that alpha-synuclein does not play a role in risky decision making as evaluated in the mIGT

Use of recombinant inbred mouse strains to study genetic basis of motor impulsivity and compulsivity in 5-choice serial reaction time task

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