Brain functional connectivity correlates of autism diagnosis and familial liability in 24-month-olds.

Background: fcMRI correlates of autism spectrum disorder (ASD) diagnosis and familial liability were studied in 24-month-olds at high (older affected sibling) and low familial likelihood for ASD.

Methods: fcMRI comparisons of high-familial-likelihood (HL) ASD-positive (HLP, N = 23) and ASD-negative (HLN, N = 91), and low-likelihood ASD-negative (LLN, N = 27) 24-month-olds from the Infant Brain Imaging Study (IBIS) Network were conducted, employing object oriented data analysis (OODA), support vector machine (SVM) classification, and network-level fcMRI enrichment analyses.

Results: OODA (alpha = 0.

Functional connectivity between the visual and salience networks and autistic social features at school-age.

Background: Autism spectrum disorder (ASD) is highly heritable and phenotypically variable. Neuroimaging markers reflecting variation in behavior will provide insights into circuitry subserving core features. We examined functional correlates of ASD symptomology at school-age, while accounting for associated behavioral and cognitive domains, in a longitudinal sample followed from infancy and enriched for those with a genetic liability for ASD.

Statistical properties of functional connectivity MRI enrichment analysis in school-age autism research.

Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations.

The emergency department trigger tool: Multicenter trigger query validation.

Objectives: We previously described derivation and validation of the emergency department trigger tool (EDTT) for adverse event (AE) detection. As the first step in our multicenter study of the tool, we validated our computerized screen for triggers against manual review, establishing our use of this automated process for selecting records to review for AEs.

Methods: This is a retrospective observational study of visits to three urban, academic EDs over 18 months by patients ≥ 18 years old.

Near-Miss Events Detected Using the Emergency Department Trigger Tool.

Objectives: Near misses include conditions with potential for harm, intercepted medical errors, and events requiring monitoring or intervention to prevent harm. Little is reported on near misses or their importance for quality and safety in the emergency department (ED).

Methods: This is a secondary evaluation of data from a retrospective study of the ED Trigger Tool (EDTT) at an urban, academic ED (data from October 1, 2014, to October 31, 2015; 92,859 eligible visits).

Emergency Department Adverse Events Detected Using the Emergency Department Trigger Tool.

Study Objective: The Emergency Department Trigger Tool (EDTT) is a novel approach to adverse event detection in the ED. We previously described the derivation, validation, and high-level performance of this tool. Here we further detail adverse events detected to demonstrate the utility of the EDTT and how it might be used for quality improvement.

The Emergency Department Trigger Tool: Validation and Testing to Optimize Yield.

Objective: Recognized as a premier approach for adverse event (AE) detection, trigger tools have been developed for multiple clinical settings outside the emergency department (ED). We recently derived and tested an ED trigger tool (EDTT) with enhanced features for high-yield detection of harm, consisting of 30 triggers associated with AEs. In this study, we validate the EDTT in an independent sample and compare record selection approaches to optimize yield for quality improvement.

Adverse Events Present on Arrival to the Emergency Department: The ED as a Dual Safety Net.

Background: The emergency department (ED) is the natural venue for the provision of acute unscheduled care. However, little is known about the nature and proportion of this care that goes to addressing adverse events (AEs)-physical injury to a patient due to health care that requires some intervention-that are present on arrival (POA) to the ED. Described here are AEs that are POA, and population prevalence estimates for these events.

The Emergency Department Trigger Tool: A Novel Approach to Screening for Quality and Safety Events.

Study Objective: Trigger tools improve surveillance for harm by focusing reviews on records with "triggers" whose presence increases the likelihood of an adverse event. We refine and automate a previously developed emergency department (ED) trigger tool and present record selection strategies to further optimize yield.

Methods: We specified 97 triggers for extraction from our electronic medical record, identifying 76,894 ED visits with greater than or equal to 1 trigger.

Critical Review, Development, and Testing of a Taxonomy for Adverse Events and Near Misses in the Emergency Department.

Objectives: An adverse event (AE) is a physical harm experienced by a patient due to health care, requiring intervention. Describing and categorizing AEs is important for quality and safety assessment and identifying areas for improvement. Safety science suggests that improvement efforts should focus on preventing and mitigating harm rather than on error, which is commonplace but infrequently leads to AEs.

Multicenter Test of an Emergency Department Trigger Tool for Detecting Adverse Events.

Objectives: Traditional approaches to safety and quality screening in the emergency department (ED) are porous and low yield for identifying adverse events (AEs). A better approach may be in the use of trigger tool methodology. We recently developed a novel ED trigger tool using a multidisciplinary, multicenter approach.

Inhibitory control in siblings discordant for exposure to maternal smoking during pregnancy.

Maternal smoking during pregnancy (SDP) has been linked to poorer offspring executive function across development, but SDP does not occur independent of other familial risk factors. As such, poor and inconsistent control for potential confounds, notably shared familial (i.e.

Prenatal Exposure Effects on Early Adolescent Substance Use: Preliminary Evidence From a Genetically Informed Bayesian Approach.

Objective: Given the controversy surrounding the question of whether there are direct or causal effects of exposure to maternal smoking during pregnancy (SDP) on offspring outcomes such as substance use during the adolescent years, we sought to test, on a preliminary basis, within- and between-family associations of SDP and initiation of substance use early in adolescence (by age 15 years) using a discordant sibling design.

Method: We used a sibling-comparison approach in a sample of 173 families drawn from the state of Missouri, wherein mothers were discordant for smoking behaviors between two different pregnancies, to test for associations of SDP and initiation of substance use in a younger adolescent cohort. The discordant sibling comparison approach allows for disentangling familial effects from direct effects of SDP through the purposeful collection of data from siblings within the same family with differential exposure.

Within-Family Effects of Smoking during Pregnancy on ADHD: the Importance of Phenotype.

We sought to test within- and between- family associations of smoking during pregnancy (SDP) and attention deficit-hyperactivity disorder (ADHD) symptoms using a structured interview based on the conventional Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) symptoms and the Strengths and Weaknesses of ADHD-Symptoms and Normal-Behavior (SWAN) scale, which is a population based measure that grew out of the notion that an ADHD diagnosis exists on the extreme end of a continuum of normative behaviors and includes both above- and below- average performance on attention and activity. We used a sibling-comparison approach in a sample of 173 families including siblings aged 7-16 years (52% male) drawn from the state of Missouri, USA, wherein mothers smoked during one pregnancy but not the other. There was a within-family effect of smoking during pregnancy on SWAN hyperactivity/impulsivity and SWAN total ADHD behaviors.

The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders.

Introduction: Forms of childhood trauma tend to co-occur and are associated with increased risk for psychiatric and substance use disorders. Commonly used binary measures of trauma exposure have substantial limitations.

Methods: We performed multigroup confirmatory factor analysis (CFA), separately by sex, using data from the Childhood Trauma (CT) Study's sample of twins and siblings (N = 2594) to derive three first-order factors (childhood physical abuse, childhood sexual abuse, and parental partner abuse) and, as hypothesized, one higher order, childhood trauma factor (CTF) representing a measure of their common variance.

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects.

Unopposed cathepsin G, neutrophil elastase, and proteinase 3 cause severe lung damage and emphysema.

Cigarette smoking is a major factor for the development of pulmonary emphysema because it induces abnormal inflammation and a protease-rich local milieu that causes connective tissue breakdown of the lungs. As a result of its capacity to degrade lung tissue and the high risk of patients lacking α1-antitrypsin to develop emphysema, much interest has focused on neutrophil elastase (NE). Two similar neutrophil serine proteases (NSPs), cathepsin G and proteinase 3, coexist with NE in humans and mice, but their potential tissue-destructive role(s) remains unclear.

Attention-Deficit/Hyperactivity Disorder, Autistic Traits, and Substance Use Among Missouri Adolescents.

Background: Although existing literature demonstrates the association of attention-deficit/hyperactivity disorder (ADHD) with both substance use (SU) and autism spectrum disorder (ASD), few studies have examined rates of SU among adolescents with elevated ASD symptoms, with or without comorbid ADHD. Clinic-based studies suggest a possible protective effect of ASD against SU, but this has not been confirmed in population-based studies.

Objective: We examined alcohol, tobacco, and drug use in adolescents with either ADHD, elevated autistic traits, or both as compared with controls.

Exploration of ADHD Subtype Definitions and Co-Occurring Psychopathology in a Missouri Population-Based Large Sibship Sample.

Background: There is some debate regarding the utility of Attention-Deficit/ Hyperactivity Disorder (ADHD) subtypes as currently defined. Differences in co-occurring psychopathology among subtypes would support the validity of subtype definitions.

Objective: To explore how ADHD subtype relates to co-occurring psychopathology in a large population-based sample of children and adolescents (n=5744).

Genetic variation in the serotonin transporter and HTR1B receptor predicts reduced bone formation during serotonin reuptake inhibitor treatment in older adults.

Objectives: Studies have reported an association between serotonin reuptake inhibitors (SRIs) and accelerated bone loss. Genetic variation in the serotonin system might modulate bone metabolism changes during SRI treatment. In a clinical trial we examined functional genetic polymorphisms of serotonin transporter and receptors involved in bone metabolism to determine whether they predict changes in bone metabolism during SRI treatment.

PTSD risk associated with a functional DRD2 polymorphism in heroin-dependent cases and controls is limited to amphetamine-dependent individuals.

Posttraumatic stress disorder (PTSD), a pathologic response to severe stress, is a common co-morbid disorder in substance-dependent individuals. Evidence from twin studies suggests that PTSD is moderately heritable. Genetic association studies to date have reported a limited number of replicated findings.

ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.

Context: The genetic contribution to liability for opioid dependence is well established; identification of the responsible genes has proved challenging.

Objective: To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations.

Design: Case-control genetic association study that included 2 control groups (lacking an established optimal control group).

Examining the association of NRXN3 SNPs with borderline personality disorder phenotypes in heroin dependent cases and socio-economically disadvantaged controls.

Background: Borderline personality disorder (BPD) and substance use disorders frequently co-occur; their dual presence predicts poor prognosis. The genetic underpinnings of BPD have not been well-characterized and could offer insight into comorbidity. The current report focuses on the association of neurexin 3 (NRXN3) single nucleotide polymorphisms (SNPs) with BPD symptoms in heroin dependent cases and controls.

Association of OPRD1 polymorphisms with heroin dependence in a large case-control series.

Genes encoding the opioid receptors (OPRM1, OPRD1 and OPRK1) are obvious candidates for involvement in risk for heroin dependence. Prior association studies commonly had samples of modest size, included limited single nucleotide polymorphism (SNP) coverage of these genes and yielded inconsistent results. Participants for the current investigation included 1459 heroin-dependent cases ascertained from maintenance clinics in New South Wales, Australia, 1495 unrelated individuals selected from an Australian sample of twins and siblings as not meeting DSM-IV criteria for lifetime alcohol or illicit drug dependence (non-dependent controls) and 531 controls ascertained from economically disadvantaged neighborhoods in proximity to the maintenance clinics.