The Cognitive Impact of the ANK3 Risk Variant for Bipolar Disorder: Initial Evidence of Selectivity to Signal Detection during Sustained Attention

BACKGROUND: Abnormalities in cognition have been reported in patients with Bipolar Disorder (BD) and their first degree relatives, suggesting that susceptibility genes for BD may impact on cognitive processes. Recent genome-wide genetic studies have reported a strong association with BD in a single nucleotide polymorphism (SNP) (rs10994336) within ANK3, which codes for Ankyrin 3. This protein is involved in facilitating the propagation of action potentials by regulating the assembly of sodium gated ion channels. Since ANK3 influences the efficiency of transmission of neuronal impulses, allelic variation in this gene may have widespread cognitive effects. Preclinical data suggest that this may principally apply to sequential signal detection, a core process of sustained attention. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and eighty-nine individuals of white British descent were genotyped for the ANK3 rs10994336 polymorphism and received diagnostic interviews and comprehensive neurocognitive assessment of their general intellectual ability, memory, decision making, response inhibition and sustained attention. Participants comprised euthymic BD patients (n = 47), their unaffected first-degree relatives (n = 75) and healthy controls (n = 67). The risk allele T was associated with reduced sensitivity in target detection (p = 0.0004) and increased errors of commission (p = 0.0018) during sustained attention regardless of diagnosis. We found no effect of the ANK3 genotype on general intellectual ability, memory, decision making and response inhibition. CONCLUSIONS/SIGNIFICANCE: Our results suggest that allelic variation in ANK3 impacts cognitive processes associated with signal detection and this mechanism may relate to risk for BD. However, our results require independent replication and confirmation that ANK3 (rs10994336) is a direct functional variant

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Prevalência de transtornos mentais nas tentativas de suicídio em um hospital de emergência no Rio de Janeiro, Brasil Prevalence of mental disorders associated with suicide attempts treated at an emergency hospital in Rio de Janeiro, Brazil

Há poucos estudos nacionais sobre prevalência de transtornos mentais nas tentativas de suicídio, os quais utilizararam principalmente dados secundários e instrumentos de rastreamento. O objetivo deste estudo foi estimar a prevalência de transtornos mentais em 96 casos de tentativas de suicídio atendidos em hospital de emergência, Rio de Janeiro, Brasil (2006-2007), utilizando o Composite International Development Interview. A maioria da amostra consistiu em mulheres, jovens, baixa escolaridade e ingestão de medicamentos psicoativos como principal meio. Outros fatores: histórias prévias de tentativa e uso de álcool no momento do agravo. Os transtornos mentais mais freqüentes foram: episódio depressivo (38,9%), dependência de substâncias psicoativas (21,9%), transtorno de estresse pós-traumático (20,8%), dependência de álcool (17,7%) e esquizofrenia (15,6%). A taxa total dos transtornos mentais foi de 71,9%. Tais achados são mais próximos aos estudos em países em desenvolvimento. Além do acesso ao tratamento dos transtornos mentais, são necessárias políticas públicas que enfatizem o controle de meios e respostas sociais à redução do comportamento suicida.<br>There are few Brazilian studies on prevalence of mental disorders in suicide attempters. The available studies have mainly used secondary data and screening instruments. The principal objective of this study was to estimate the prevalence of mental disorders in 96 suicide attempters seen in an emergency ward in Rio de Janeiro, Brasil (2006-2007) using the Composite International Development Interview. Most were female, young, and illiterate, and the main method was ingestion of psychoactive drugs. Other factors included history of prior attempts and use of alcohol at the time of attempt. The most frequent mental disorders were: depression (38.9%), use of psychoactive substances (21.9%), posttraumatic stress disorder (20.8%), alcohol abuse (17.7%), and schizophrenia (15.6%). Total prevalence of mental disorders was 71.9%. These findings are largely consistent with studies conducted in other developing countries. Besides access to treatment for mental disorders, public policies with an emphasis on the control of suicide methods and social responses for the reduction of suicidal behavior are needed