Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities.

Understanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology and treatment of psychopathology. Here, we combine transdiagnostic and dimensional approaches to genetic discovery for the first time, conducting a novel multivariate genome-wide association study of eight psychiatric symptoms and disorders broadly related to mood disturbance and psychosis. We identify two transdiagnostic genetic liabilities that distinguish between common forms of psychopathology versus rarer forms of serious mental illness.

Classifying Characteristics of Opioid Use Disorder From Hospital Discharge Summaries Using Natural Language Processing.

Background: Opioid use disorder (OUD) is underdiagnosed in health system settings, limiting research on OUD using electronic health records (EHRs). Medical encounter notes can enrich structured EHR data with documented signs and symptoms of OUD and social risks and behaviors. To capture this information at scale, natural language processing (NLP) tools must be developed and evaluated.

Variability and concordance of sulcal patterns in the orbitofrontal cortex: A twin study.

Sulcogyral patterns have been identified in the orbitofrontal cortex (OFC) based on the continuity of the medial and lateral orbital sulci. Pattern types are named according to their frequency in the population, with Type I present in ∼60%, Type II in ∼25%, Type III in ∼10%, and Type IV in ∼5%. Previous work has demonstrated that psychiatric conditions with high estimated heritability (e.

Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology.

Rare genomic disorders (RGDs) confer elevated risk for neurodevelopmental psychiatric disorders. In this era of intense genomics discoveries, the landscape of RGDs is rapidly evolving. However, there has not been comparable progress to date in scalable, harmonized phenotyping methods.

Defining the Critical Components of Informed Consent for Genetic Testing.

Purpose: Informed consent for genetic testing has historically been acquired during pretest genetic counseling, without specific guidance defining which core concepts are required.

Methods: The Clinical Genome Resource (ClinGen) Consent and Disclosure Recommendations Workgroup (CADRe) used an expert consensus process to identify the core concepts essential to consent for clinical genetic testing. A literature review identified 77 concepts that are included in informed consent for genetic tests.

Engaging Parents and Health Care Stakeholders to Inform Development of a Behavioral Intervention Technology to Promote Pediatric Behavioral Health: Mixed Methods Study.

Background: Despite effective psychosocial interventions, gaps in access to care persist for youth and families in need. Behavioral intervention technologies (BITs) that apply psychosocial intervention strategies using technological features represent a modality for targeted prevention that is promising for the transformation of primary care behavioral health by empowering parents to take charge of the behavioral health care of their children. To realize the potential of BITs for parents, research is needed to understand the status quo of parental self-help and parent-provider collaboration to address behavioral health challenges and unmet parental needs that could be addressed by BITs.

Developmental Histories Facilitating the Emergence of Creative Scientific Expertise: The Role of Developed Cognitive Talents, Education, and Social and Cultural Contexts.

Understanding how individual and contextual factors collectively contribute to the developmental histories that facilitate the emergence of creative expertise in science is improved by considering the contribution of the broad structure of developed cognitive abilities to creativity, prospective research on the high achieving or gifted students who may choose careers in and end up as creative scientists later in life, as well as retrospective studies of established creative scientists themselves and what their educational histories reveal. We first review and elaborate on these connections as documented in research which explore the development of talent, including cognitive mechanisms that include math and spatial reasoning and science related educational opportunities. We propose a research thought experiment that utilizes the multi-trait, multi-method matrix, and bifactor modeling to help understand the true overlap between measurement structures of cognitive and creative aptitudes.

Comprehensive Assessment of Visual Perceptual Skills in Autism Spectrum Disorder.

The purpose of the current study was to assess meaningful variability in visual-perceptual skills using a standardized assessment of visual perception, the Test of Visual Perceptual Skills (TVPS), across children with and without autism spectrum disorder (ASD). In addition to assessing overall accuracy across subtests of the TVPS, we also assessed response variability at the item-level, and the linear relationship between quantitative measures of ASD symptoms, task performance, and item-level variance. We report a significant linear relationship between ASD features and performance on the TVPS Figure Ground subtest.

Effect of Targeted Behavioral Science Messages on COVID-19 Vaccination Registration Among Employees of a Large Health System: A Randomized Trial.

This randomized trial evaluates whether individually addressed emails designed with behaviorally informed features increase COVID-19 vaccination rates.

A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor's appointment.

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment ( = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%.

Can You Ever Be Too Smart for Your Own Good? Comparing Linear and Nonlinear Effects of Cognitive Ability on Life Outcomes.

Despite a long-standing expert consensus about the importance of cognitive ability for life outcomes, contrary views continue to proliferate in scholarly and popular literature. This divergence of beliefs presents an obstacle for evidence-based policymaking and decision-making in a variety of settings. One commonly held idea is that greater cognitive ability does not matter or is actually harmful beyond a certain point (sometimes stated as > 100 or 120 IQ points).

Informing patients that they are at high risk for serious complications of viral infection increases vaccination rates.

For many vaccine-preventable diseases like influenza, vaccination rates are lower than optimal to achieve community protection. Those at high risk for infection and serious complications are especially advised to be vaccinated to protect themselves. Using influenza as a model, we studied one method of increasing vaccine uptake: informing high-risk patients, identified by a machine learning model, about their risk status.

Putting the Self in Self-Correction: Findings From the Loss-of-Confidence Project.

Science is often perceived to be a self-correcting enterprise. In principle, the assessment of scientific claims is supposed to proceed in a cumulative fashion, with the reigning theories of the day progressively approximating truth more accurately over time. In practice, however, cumulative self-correction tends to proceed less efficiently than one might naively suppose.

Pediatric Head CT: Automated Quantitative Analysis with Quantile Regression.

Background And Purpose: Together with quantile regression methods, such a model would have the potential for clinical utility through automated quantitative comparison of individual cases relative to their age and gender-matched peer group. Our aim was to demonstrate the automated processing of digital clinical head CT data in the development of a clinically useful model of age-related changes of the brain in the first 2 decades of life.

Materials And Methods: A total of 415 (209 female) consecutive, clinical head CTs with radiographically normal findings from patients from birth through 20 years of age were retrospectively selected and subjected to automated segmentation.

Objecting to experiments even while approving of the policies or treatments they compare.

We resolve a controversy over two competing hypotheses about why people object to randomized experiments: 1) People unsurprisingly object to experiments only when they object to a policy or treatment the experiment contains, or 2) people can paradoxically object to experiments even when they approve of implementing either condition for everyone. Using multiple measures of preference and test criteria in five preregistered within-subjects studies with 1,955 participants, we find that people often disapprove of experiments involving randomization despite approving of the policies or treatments to be tested.

Clinical outcomes of a genomic screening program for actionable genetic conditions.

Purpose: Three genetic conditions-hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia-have tier 1 evidence for interventions that reduce morbidity and mortality, prompting proposals to screen unselected populations for these conditions. We examined the impact of genomic screening on risk management and early detection in an unselected population.

Methods: Observational study of electronic health records (EHR) among individuals in whom a pathogenic/likely pathogenic variant in a tier 1 gene was discovered through Geisinger's MyCode project.

Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers.

Individuals with 16p11.2 copy number variant (CNV) show considerable phenotypic heterogeneity. Although autism spectrum disorder (ASD) is reported in approximately 20-23% of individuals with 16p11.

Insufficient Evidence for "Autism-Specific" Genes.

Despite evidence that deleterious variants in the same genes are implicated across multiple neurodevelopmental and neuropsychiatric disorders, there has been considerable interest in identifying genes that, when mutated, confer risk that is largely specific for autism spectrum disorder (ASD). Here, we review the findings and limitations of recent efforts to identify relatively "autism-specific" genes, efforts which focus on rare variants of large effect size that are thought to account for the observed phenotypes. We present a divergent interpretation of published evidence; discuss practical and theoretical issues related to studying the relationships between rare, large-effect deleterious variants and neurodevelopmental phenotypes; and describe potential future directions of this research.

Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer.

Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin.

Behavioural profiling of autism connectivity abnormalities.

Background: Brain regions are functionally diverse, and a given region may engage in a variety of tasks. This functional diversity of brain regions may be one factor that has prevented the finding of consistent biomarkers for brain disorders such as autism spectrum disorder (ASD). Thus, methods to characterise brain regions would help to determine how functional abnormalities contribute to affected behaviours.

Self-distancing promotes positive emotional change after adversity: Evidence from a micro-longitudinal field experiment.

Objective: This research examines changes in emotionality following adverse experiences in daily life. We tested whether daily self-distancing (vs. self-immersing) in reflections on adversity results in positive change in emotionality.

Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems.

Objective: Individuals at high risk for schizophrenia may benefit from early intervention, but few validated risk predictors are available. Genetic profiling is one approach to risk stratification that has been extensively validated in research cohorts. The authors sought to test the utility of this approach in clinical settings and to evaluate the broader health consequences of high genetic risk for schizophrenia.