Phenotypic and measurement influences on heritability estimates in childhood ADHD

Twin studies described a strongly heritable component of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. However, findings varied considerably between studies. In addition, ADHD presents with a high rate of comorbid disorders and associated psychopathology. Therefore, this literature review reports findings from population-based twin studies regarding the influence of subtypes, assessment instruments, rater effects, sex differences, and comorbidity rates on ADHD heritability estimates. In addition, genetic effects on the persistence of ADHD are discussed. By reviewing relevant factors influencing heritability estimates more homogeneous subtypes relevant for molecular genetic studies can be elicited. A systematic search of population-based twin studies in ADHD was performed, using the databases PubMed and PsycInfo. Results of family studies were added in case insufficient or contradictory findings were obtained in twin studies. Heritability estimates were strongly influenced by rater effects and assessment instruments. Inattentive and hyperactive–impulsive symptoms were likely influenced by common as well as specific genetic risk factors. Besides persistent ADHD, ADHD accompanied by symptoms of conduct or antisocial personality disorder might be another strongly genetically determined subtype, however, family environmental risk factors have also been established for this pattern of comorbidity

Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach - unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. the median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. in addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Institute of Mental HealthNovartisJanssen-CilagAbbottEli-LillyShireBristol-Myers SquibbUniv Fed ABC, Ctr Math Computat & Cognit, Santo Andre, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilHosp Clin Porto Alegre, Child & Adolescent Psychiat Div, ADHD Outpatient Program, Porto Alegre, RS, BrazilNYU, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY USAInst Nacl Psiquiatria Desenvolvimento, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Lab Interdisciplinar Neurociencias Clin, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psychiat, São Paulo, BrazilNational Institute of Mental Health: R01MH083246Web of Scienc

An ecologic study

Background: Vancomycin-resistant enterococci (VRE) are among the most common antimicrobial-resistant pathogens causing nosocomial infections. Although antibiotic use has been identified as a risk factor for VRE, it remains unclear which antimicrobial agents particularly facilitate VRE selection. Here, we assessed whether use of specific antimicrobial agents is independently associated with healthcare-associated (HA) VRE rates in a university hospital setting in Berlin, Germany . Methods: We conducted the study between January 2014 and December 2015 at the Charité-university hospital of Berlin, Germany. From the hospital pharmacy, we extracted data for all antibacterials for systemic use (anatomical therapeutic chemical (ATC)-classification J01) and calculated ward specific antibiotic consumption in defined daily doses (DDDs) per 100 patient-days (PD). We used the microbiology laboratory database to identify all patients with isolation of invasive or non-invasive VRE and calculated HA-VRE incidence as nosocomial VRE-cases per 100 patients and HA-VRE incidence density as nosocomial VRE- cases per 1000 PD. We defined VRE isolates as hospital-acquired if they were identified three days or later after hospital admission and otherwise as community-acquired (CA-VRE). We performed univariable and multivariable regression analyses to estimate the association of the frequency of HA-VRE per month with antibiotic use and other parameters such as length of stay, type of ward or presence of at least one CA-VRE on ward. In a second analysis, we considered only patients with VRE infections. Results: We included data from 204,054 patients with 948,380 PD from 61 wards. Overall, 1430 VRE-cases were identified of which 409 (28.6%) were considered hospital-acquired (HA). We found that carbapenem use in the current month and prior-month use of glycopeptides increased the risk for HA-VRE by 1% per 1 DDD/100 PD and 3% per 1 DDD/100 PD, respectively. However, when only VRE from clinical samples were considered, only glycopeptide use showed a statistically significant association. In both models, detection of at least one patient with CA-VRE on a ward in the current month significantly increased the risk of HA-VRE, thereby indicating nosocomial spread of VRE. Conclusions: Our findings suggest that the risk of HA-VRE is associated with specific antimicrobial agents. Prudent use of these antimicrobial agents might reduce nosocomial VRE rates. That appearance of at least one CA-VRE case on the ward increased the risk of HA-VRE detection highlights the importance of strict hand hygiene practices to interrupt person-to-person transmission of VRE

Cost-Effectiveness of Routine Screening for Cardiac Toxicity in Patients Treated with Imatinib in Brazil

AbstractWe performed a cost-effectiveness study of different strategies of screening for cardiotoxicity in patients receiving imatinib, the first strategy based on yearly echocardiograms in all patients and the second strategy based on yearly B-type natriuretic peptide level measurement, reserving echocardiograms for patients with an abnormal test result. Results are presented in terms of additional cost per diagnosis as compared with not performing any screening. From the Brazilian private sector’s perspective, strategies 1 and 2 resulted in additional costs of US $30,951.53 and US$19,925.64 per diagnosis of cardiotoxicity, respectively. From the perspective of the Brazilian public health system, the same strategies generated additional costs of US $7,668.00 and US$20,232.87 per diagnosis, respectively. In our study, systematic screening for cardiotoxicity in patients using imatinib has a high cost per diagnosis. If screening is to be adopted, a strategy based on B-type natriuretic peptide level measurement, reserving echocardiography for patients with abnormal results, results in lower costs per diagnosis in the private sector. From the public health system’s perspective, costs per diagnosis will greatly depend on the reimbursement values adopted for B-type natriuretic peptide level measurement

Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction

Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI

Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84–98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention

Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL), DSM-5 update: translation into Brazilian Portuguese

Brazilian governmental research funding agency Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Brazilian governmental research funding agency Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Brazilian governmental research funding agency Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS)ShireNovartisEli LillyJanssen-CilagUniv Fed Rio Grande do Sul, Fac Med, Dept Psiquiatria, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Fac Med, Dept Pediat, Porto Alegre, RS, BrazilUniv Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilPontifica Univ Catolica Rio Grande do Sul, Dev Cognit Neurosci Res Grp GNCD, Porto Alegre, RS, BrazilInst Bairral Psiquiatria, Ctr Integrado Desenvolvimento Infancia & Adolesce, Itapira, BrazilUniv Fed Sao Paulo, Fac Med, Dept & Inst Psiquiatria, Sao Paulo, SP, BrazilWeb of Scienc

Specific and social fears in children and adolescents: separating normative fears from problem indicators and phobias

Objective: To distinguish normative fears from problematic fears and phobias. Methods: We investigated 2,512 children and adolescents from a large community school-based study, the High Risk Study for Psychiatric Disorders. Parent reports of 18 fears and psychiatric diagnosis were investigated. We used two analytical approaches: confirmatory factor analysis (CFA)/item response theory (IRT) and nonparametric receiver operating characteristic (ROC) curve. Results: According to IRT and ROC analyses, social fears are more likely to indicate problems and phobias than specific fears. Most specific fears were normative when mild; all specific fears indicate problems when pervasive. In addition, the situational fear of toilets and people who look unusual were highly indicative of specific phobia. Among social fears, those not restricted to performance and fear of writing in front of others indicate problems when mild. All social fears indicate problems and are highly indicative of social phobia when pervasive. Conclusion: These preliminary findings provide guidance for clinicians and researchers to determine the boundaries that separate normative fears from problem indicators in children and adolescents, and indicate a differential severity threshold for specific and social fears