Big five personality traits and common mental disorders within a hierarchical taxonomy of psychopathology: A longitudinal study of Mexican-origin youth.

The present study (a) tested whether a structure of common mental disorders within the hierarchical taxonomy of psychopathology was invariant from late childhood to adolescence in a sample of Mexican-origin youth, (b) examined the developmental course of psychopathology at different levels of the hierarchy, and (c) tested the degree to which changes in psychopathology were associated with changes in the Big Five personality domains. Results were consistent with the longitudinal hierarchical invariance of common mental disorders from age 12 to 17 ( = 674). Further, initial levels of conscientiousness, agreeableness, and emotional stability were positively associated with lower initial levels of a higher order factor of psychopathology, and increases in extraversion and decreases in neuroticism were associated with decreases in a higher order factor of psychopathology, which captured the general tendency for externalizing, internalizing, and attention-hyperactivity-related dimensions of psychopathology to correlate.

The causal influence of brain size on human intelligence: Evidence from within-family phenotypic associations and GWAS modeling.

There exists a moderate correlation between MRI-measured brain size and the general factor of IQ performance (), but the question of whether the association reflects a theoretically important causal relationship or spurious confounding remains somewhat open. Previous small studies ( < 100) looking for the persistence of this correlation within families failed to find a tendency for the sibling with the larger brain to obtain a higher test score. We studied the within-family relationship between brain volume and intelligence in the much larger sample provided by the Human Connectome Project ( = 1,022) and found a highly significant correlation (disattenuated = 0.

Para-limbic Structural Abnormalities Are Associated With Internalizing Symptoms in Children With Prenatal Alcohol Exposure.

Background: Prenatal alcohol exposure (PAE) is associated with a variety of structural abnormalities in the brain, including several within the para-limbic system. Children with PAE have higher rates of internalizing disorders, including depression and anxiety, which may be related to underlying limbic system anomalies.

Methods: Children aged 8 to 16 with PAE (n = 41) or without PAE (n = 36) underwent an magnetic resonance imaging of the brain and parents completed behavioral questionnaires about their children.

Differential implications of persistent, remitted, and late-onset ADHD symptoms for substance abuse in women and men: A twin study from ages 11 to 24.

Background: Persistence and emergence of ADHD in adulthood are associated with substance problems. We investigate differential implications of ADHD course for tobacco, alcohol, or marijuana problems by sex, then whether substance misuse results from ADHD or contributes to it, through a twin differences design.

Methods: A population-based cohort of 998 twins (61 % monozygotic; 52 % female), born in Minnesota from 1988 to 1994, was prospectively assessed from ages 11-24.

CpTi(κBuNCNBu): A Complex with an Unusual κ Coordination Mode of a Heterocumulene Featuring a Free Carbene.

Although there are myriad binding modes of heterocumulenes to metal centers, the monometallic κ-ECE (E = O, S, NR) coordination mode has not been reported. Herein, the synthesis, isolation, and physical characterization of CpTi(κ-BuNCNBu) () (Cp = cyclopentadienyl, Bu = -butyl), a strained 4-membered metallacycle bearing a free carbene, is described. Computational (DFT, CASSCF, QT-AIM, ELF) and solid-state CP-MAS C NMR spectroscopic analysis indicate that is best described as a free carbene with partial Ti-C bonding that results from Ti-N π-bonding mixing with N-C-N σ-bonding of the bent N-C-N framework.

Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder.

Background: Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial.

Adolescent Externalizing Psychopathology and Its Prospective Relationship to Marijuana Use Development from Age 14 to 30: Replication Across Independent Longitudinal Twin Samples.

Externalizing psychopathology in early adolescence is a highly heritable risk factor for drug use, yet how it relates to marijuana use development is not well-characterized. We evaluate this issue in independent twin samples from Colorado (N = 2608) and Minnesota (N = 3630), assessed from adolescence to early adulthood. We used a biometric latent growth model of marijuana use frequency with data from up to five waves of assessment from ages 14 to 30, to examine change in marijuana use and its relationship with a factor model of adolescent externalizing psychopathology.

Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis.

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters.

NosP Signaling Modulates the NO/H-NOX-Mediated Multicomponent c-Di-GMP Network and Biofilm Formation in .

Biofilms form when bacteria aggregate in a self-secreted exopolysaccharide matrix; they are resistant to antibiotics and implicated in disease. Nitric oxide (NO) is known to mediate biofilm formation in many bacteria via ligation to H-NOX (heme-NO/oxygen binding) domains. Most NO-responsive bacteria, however, lack H-NOX domain-containing proteins.

Enhancing subtilisin thermostability through a modified normalized B-factor analysis and loop-grafting strategy.

Rational design-guided improvement of protein thermostability typically requires identification of residues or regions contributing to instability and introduction of mutations into these residues or regions. One popular method, B-FIT, utilizes B-factors to identify unstable residues or regions and combines them with other strategies, such as directed evolution. Here, we performed structure-based engineering to improve the thermostability of the subtilisin E-S7 (SES7) peptidase.

The NKCC1 antagonist bumetanide mitigates interneuronopathy associated with ethanol exposure in utero.

Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave.

The role of parental genotype in predicting offspring years of education: evidence for genetic nurture.

Similarities between parent and offspring are widespread in psychology; however, shared genetic variants often confound causal inference for offspring outcomes. A polygenic score (PGS) derived from genome-wide association studies (GWAS) can be used to test for the presence of parental influence that controls for genetic variants shared across generations. We use a PGS for educational attainment (EA3; N ≈ 750 thousand) to predict offspring years of education in a sample of 2517 twins and both parents.

Effectiveness and Safety of Ankle Arthrodesis Versus Arthroplasty: A Prospective Multicenter Study.

Background: Newer designs and techniques of total ankle arthroplasty (TAA) have challenged the assumption of ankle arthrodesis (AA) as the primary treatment for end-stage ankle arthritis. The objective of this study was to compare physical and mental function, ankle-specific function, pain intensity, and rates of revision surgery and minor complications between these 2 procedures and to explore heterogeneous treatment effects due to age, body mass index (BMI), patient sex, comorbidities, and employment on patients treated by 1 of these 2 methods.

Methods: This was a multisite prospective cohort study comparing outcomes of surgical treatment of ankle arthritis.

Long-Term Outcome of a Brief Intervention to Address Adolescent Drug Abuse in a School Setting.

The present study used data from a randomized controlled trial on brief interventions with adolescents to identify distinct longitudinal patterns of substance use and identify predictors, as well as outcomes associated with those use patterns. Data were originally collected for the purpose of evaluating two brief intervention conditions with adolescents who had been identified in a school setting as abusing alcohol or other drugs (total sample, = 315). Adolescents were randomly assigned to a two-session adolescent only brief intervention (BI-A), a two-session adolescent- plus an additional parent session (BI-AP), or an assessment only control session (CON).

A new regulatory mechanism for Raf kinase activation, retinoic acid-bound Crabp1.

The rapidly accelerated fibrosarcoma (Raf) kinase is canonically activated by growth factors that regulate multiple cellular processes. In this kinase cascade Raf activation ultimately results in extracellular regulated kinase 1/2 (Erk1/2) activation, which requires Ras binding to the Ras binding domain (RBD) of Raf. We recently reported that all-trans retinoic acid (atRA) rapidly (within minutes) activates Erk1/2 to modulate cell cycle progression in stem cells, which is mediated by cellular retinoic acid binding protein 1 (Crabp1).

Persistent Changes in Stress-Regulatory Genes in Pregnant Women or Children Exposed Prenatally to Alcohol.

Background: We have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE).

Opportunities for the prevention of mental disorders by reducing general psychopathology in early childhood.

This paper explores the concept that reducing general psychopathology early in the life course provides unprecedented opportunities to prevent the development of all forms of psychopathology later in life. We review empirical evidence for the existence of the general factor of psychopathology and theories regarding the psychological nature of the factor. We then highlight specific examples of environmental risk factors for general psychopathology and discuss translational implications for the transdiagnostic prevention of psychopathology beginning in early childhood.

Reduced premovement positivity during the stimulus-response interval precedes errors: Using single-trial and regression ERPs to understand performance deficits in ADHD.

Brain mechanisms linked to incorrect response selections made under time pressure during cognitive task performance are poorly understood, particularly in adolescents with attention-deficit hyperactivity disorder (ADHD). Using subject-specific multimodal imaging (electroencephalogram, magnetic resonance imaging, behavior) during flanker task performance by a sample of 94 human adolescents (mean age = 15.5 years, 50% female) with varying degrees of ADHD symptomatology, we examined the degree to which amplitude features of source-resolved event-related potentials (ERPs) from brain-independent component processes within a critical (but often ignored) period in the action selection process, the stimulus-response interval, were associated with motor response errors (across trials) and error rates (across individuals).

The rsmS (ybaM) mutation causes bypass suppression of the RsmAB post-transcriptional virulence regulation system in enterobacterial phytopathogens.

Plant cell wall degrading enzymes (PCWDEs) are the primary virulence determinants of soft rotting bacteria such as the potato pathogen, Pectobacterium atrosepticum. The regulation of secondary metabolite (Rsm) system controls production of PCWDEs in response to changing nutrient conditions. This work identified a new suppressor of an rsmB mutation - ECA1172 or rsmS (rsmB suppressor).

The nonconservative CD177 single-nucleotide polymorphism c.1291G>A is a genetic determinant for human neutrophil antigen-2 atypical/low expression and deficiency.

Background: Human neutrophil antigen-2 (HNA-2) is exclusively expressed on neutrophils. HNA-2-deficient individuals (HNA-2 null) are susceptible to produce isoantibodies. The nonsense CD177 coding single-nucleotide polymorphism (SNP) c.

Reasons High School Students Use Marijuana: Prevalence and Correlations With Use Across Four Decades.

Objective: Changes in the legality and prevalence of marijuana raise questions about whether adolescents' reasons for using marijuana and associations between reasons for use and recent marijuana use have changed historically.

Method: Using nationally representative data from Monitoring the Future for 1976-2016 (N = 39,964; 47.6% female), we examined changes in self-reported reasons for marijuana use and in the associations between reasons for use and past-30-day marijuana use among 12th graders who used marijuana in the past 12 months.

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.

The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies.

To infer that a single-nucleotide polymorphism (SNP) either affects a phenotype or is linkage disequilibrium with a causal site, we must have some assurance that any SNP-phenotype correlation is not the result of confounding with environmental variables that also affect the trait. In this study, we study the properties of linkage disequilibrium (LD) Score regression, a recently developed method for using summary statistics from genome-wide association studies to ensure that confounding does not inflate the number of false positives. We do not treat the effects of genetic variation as a random variable and thus are able to obtain results about the unbiasedness of this method.

Two-year cortical trajectories are abnormal in children and adolescents with prenatal alcohol exposure.

Objectives: Cortical abnormalities in prenatal alcohol exposure (PAE) are known, including in gyrification (LGI), thickness (CT), volume (CV), and surface area (CS). This study provides longitudinal and developmental context to the PAE cortical development literature.

Experimental Design: Included: 58 children with PAE and 52 controls, ages 6-17 at enrollment, from four Collaborative Initiative on FASD (CIFASD) sites.

Associations between childhood ADHD, gender, and adolescent alcohol and marijuana involvement: A causally informative design.

Background: We report whether the etiology underlying associations of childhood ADHD with adolescent alcohol and marijuana involvement is consistent with causal relationships or shared predispositions, and whether it differs by gender.

Methods: In three population-based twin samples (N = 3762; 64% monozygotic), including one oversampling females with ADHD, regressions were conducted with childhood inattentive or hyperactive-impulsive symptoms predicting alcohol and marijuana outcomes by age 17. To determine whether ADHD effects were consistent with causality, twin difference analyses divided effects into those shared between twins in the pair and those differing within pairs.