Publications by authors named "Wesley K Thompson"

195 Publications

Comparing Copy Number Variations in a Danish Case Cohort of Individuals With Psychiatric Disorders.

JAMA Psychiatry 2021 Nov 24. Epub 2021 Nov 24.

Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen, Denmark.

Importance: Although the association between several recurrent genomic copy number variants (CNVs) and mental disorders has been studied for more than a decade, unbiased, population-based estimates of the prevalence, disease risks and trajectories, fertility, and mortality to contrast chromosomal abnormalities and advance precision health care are lacking.

Objective: To generate unbiased, population-based estimates of prevalence, disease risks and trajectories, fertility, and mortality of CNVs implicated in neuropsychiatric disorders.

Design, Setting, And Participants: In a population-based case-cohort study, using the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) 2012 database, individuals born between May 1, 1981, and December 31, 2005, and followed up until December 31, 2012, were analyzed. All individuals (n = 57 377) with attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), schizophrenia (SCZ), autism spectrum disorder (ASD), or bipolar disorder (BPD) were included, as well as 30 000 individuals randomly drawn from the database. Data analysis was conducted from July 1, 2017, to September 7, 2021.

Exposures: Copy number variants at 6 genomic loci (1q21.1, 15q11.2, 15q13.3, 16p11.2, 17p12, and 17q12).

Main Outcomes And Measures: Population-unbiased hazard ratio (HR) and survival estimates of CNV associations with the 5 ascertained psychiatric disorders, epilepsy, intellectual disability, selected somatic disorders, fertility, and mortality.

Results: Participants' age ranged from 1 to 32 years (mean, 12.0 [IQR, 6.9] years) during follow-up, and 38 662 were male (52.3%). Copy number variants broadly associated with an increased risk of autism spectrum disorder and ADHD, whereas risk estimates of SCZ for most CNVs were lower than previously reported. Comparison with previous studies suggests that the lower risk estimates are associated with a higher CNV prevalence in the general population than in control samples of most case-control studies. Significant risk of major depressive disorder (HR, 5.8; 95% CI, 1.5-22.2) and sex-specific risk of bipolar disorder (HR, 17; 95% CI, 1.5-189.3, in men only) were noted for the 1q21.1 deletion. Although CNVs at 1q21.1 and 15q13.3 were associated with increased risk across most diagnoses, the 17p12 deletion consistently conferred less risk of psychiatric disorders (HR 0.4-0.8), although none of the estimates differed significantly from the general population. Trajectory analyses noted that, although diagnostic risk profiles differed across loci, they were similar for deletions and duplications within each locus. Sex-stratified analyses suggest that pathogenicity of many CNVs may be modulated by sex.

Conclusions And Relevance: The findings of this study suggest that the iPSYCH population case cohort reveals broad disease risk for some of the studied CNVs and narrower risk for others, in addition to sex differential liability. This finding on genomic risk variants at the level of a population may be important for health care planning and clinical decision making, and thus the advancement of precision health care.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.3392DOI Listing
November 2021

Growth trajectories of cognitive and motor control in adolescence: How much is development and how much is practice?

Neuropsychology 2021 Nov 22. Epub 2021 Nov 22.

Department of Psychiatry and Behavioral Sciences.

Objective: Executive control continues to develop throughout adolescence and is vulnerable to alcohol use. Although longitudinal assessment is ideal for tracking executive function development and onset of alcohol use, prior testing experience must be distinguished from developmental trajectories.

Method: We used the Stroop Match-to-Sample task to examine the improvement of processing speed and specific cognitive and motor control over 4 years in 445 adolescents. The twice-minus-once-tested method was used and expanded to four test sessions to delineate prior experience (i.e., learning) from development. A General Additive Model evaluated the predictive value of age and sex on executive function development and potential influences of alcohol use on development.

Results: Results revealed strong learning between the first two assessments. Adolescents significantly improved their speed processing over 4 years. Compared with boys, girls enhanced ability to control cognitive interference and motor reactions. Finally, the influence of alcohol use initiation was tested over 4 years for development in 110 no/low, 110 moderate/heavy age- and sex-matched drinkers; alcohol effects were not detected in the matched groups.

Conclusions: Estimation of learning effects is crucial for examining developmental changes longitudinally. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000771DOI Listing
November 2021

Neural vulnerability and hurricane-related media are associated with post-traumatic stress in youth.

Nat Hum Behav 2021 Nov 15;5(11):1578-1589. Epub 2021 Nov 15.

Florida International University, Miami, FL, USA.

The human toll of disasters extends beyond death, injury and loss. Post-traumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable. Even children far removed from harm's way report PTS, and media-based exposure may partially account for this phenomenon. In this study, we examine this issue using data from nearly 400 9- to 11-year-old children collected before and after Hurricane Irma, evaluating whether pre-existing neural patterns moderate associations between hurricane experiences and later PTS. The 'dose' of both self-reported objective exposure and media exposure predicted PTS, the latter even among children far from the hurricane. Furthermore, neural responses in brain regions associated with anxiety and stress conferred particular vulnerability. For example, heightened amygdala reactivity to fearful stimuli moderated the association between self-reported media exposure and PTS. Collectively, these findings show that for some youth with measurable vulnerability, consuming extensive disaster-related media may offer an alternative pathway to disaster exposure that transcends geography and objective risk.
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http://dx.doi.org/10.1038/s41562-021-01216-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8607811PMC
November 2021

Associations between patterns in comorbid diagnostic trajectories of individuals with schizophrenia and etiological factors.

Nat Commun 2021 11 16;12(1):6617. Epub 2021 Nov 16.

Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.

Schizophrenia is a heterogeneous disorder, exhibiting variability in presentation and outcomes that complicate treatment and recovery. To explore this heterogeneity, we leverage the comprehensive Danish health registries to conduct a prospective, longitudinal study from birth of 5432 individuals who would ultimately be diagnosed with schizophrenia, building individual trajectories that represent sequences of comorbid diagnoses, and describing patterns in the individual-level variability. We show that psychiatric comorbidity is prevalent among individuals with schizophrenia (82%) and multi-morbidity occur more frequently in specific, time-ordered pairs. Three latent factors capture 79% of variation in longitudinal comorbidity and broadly relate to the number of co-occurring diagnoses, the presence of child versus adult comorbidities and substance abuse. Clustering of the factor scores revealed five stable clusters of individuals, associated with specific risk factors and outcomes. The presentation and course of schizophrenia may be associated with heterogeneity in etiological factors including family history of mental disorders.
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http://dx.doi.org/10.1038/s41467-021-26903-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595374PMC
November 2021

Demographic and mental health assessments in the adolescent brain and cognitive development study: Updates and age-related trajectories.

Dev Cogn Neurosci 2021 Oct 29;52:101031. Epub 2021 Oct 29.

Department of Psychiatry, University of California at San Diego, 9500 Gilman Drive (0603), La Jolla, CA 92093-0603, United States. Electronic address:

The Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and 1-year follow-up. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.
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http://dx.doi.org/10.1016/j.dcn.2021.101031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579129PMC
October 2021

Risk for depression tripled during the COVID-19 pandemic in emerging adults followed for the last 8 years.

Psychol Med 2021 Nov 2:1-8. Epub 2021 Nov 2.

Center for Health Sciences, SRI International, Menlo Park, CA, USA.

Background: The coronavirus disease 2019 (COVID-19) pandemic has significantly increased depression rates, particularly in emerging adults. The aim of this study was to examine longitudinal changes in depression risk before and during COVID-19 in a cohort of emerging adults in the U.S. and to determine whether prior drinking or sleep habits could predict the severity of depressive symptoms during the pandemic.

Methods: Participants were 525 emerging adults from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a five-site community sample including moderate-to-heavy drinkers. Poisson mixed-effect models evaluated changes in the Center for Epidemiological Studies Depression Scale (CES-D-10) from before to during COVID-19, also testing for sex and age interactions. Additional analyses examined whether alcohol use frequency or sleep duration measured in the last pre-COVID assessment predicted pandemic-related increase in depressive symptoms.

Results: The prevalence of risk for clinical depression tripled due to a substantial and sustained increase in depressive symptoms during COVID-19 relative to pre-COVID years. Effects were strongest for younger women. Frequent alcohol use and short sleep duration during the closest pre-COVID visit predicted a greater increase in COVID-19 depressive symptoms.

Conclusions: The sharp increase in depression risk among emerging adults heralds a public health crisis with alarming implications for their social and emotional functioning as this generation matures. In addition to the heightened risk for younger women, the role of alcohol use and sleep behavior should be tracked through preventive care aiming to mitigate this looming mental health crisis.
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http://dx.doi.org/10.1017/S0033291721004062DOI Listing
November 2021

A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study Cohort at Baseline.

Front Pediatr 2021 5;9:734184. Epub 2021 Oct 5.

Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, United States.

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development Study (ABCD study), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index. Further this summary will describe how physical health measures collected from the ABCD cohort compare with current normative data and clinical guidelines. We propose this data set has the potential to facilitate clinical recommendations and inform national standards of physical health in this age group. This manuscript will also provide important information for ABCD users and help guide analyses investigating physical health including new avenues for health disparity research as it pertains to adolescent and young adult development.
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http://dx.doi.org/10.3389/fped.2021.734184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526338PMC
October 2021

Risk of lead exposure, subcortical brain structure, and cognition in a large cohort of 9- to 10-year-old children.

PLoS One 2021 14;16(10):e0258469. Epub 2021 Oct 14.

Children's Hospital Los Angeles, and the Department of Pediatrics, University of Southern California, Los Angeles, California, United States of America.

Background: Lead, a toxic metal, affects cognitive development at the lowest measurable concentrations found in children, but little is known about its direct impact on brain development. Recently, we reported widespread decreases in cortical surface area and volume with increased risks of lead exposure, primarily in children of low-income families.

Methods And Findings: We examined associations of neighborhood-level risk of lead exposure with cognitive test performance and subcortical brain volumes. We also examined whether subcortical structure mediated associations between lead risk and cognitive performance. Our analyses employed a cross-sectional analysis of baseline data from the observational Adolescent Brain Cognitive Development (ABCD) Study. The multi-center ABCD Study used school-based enrollment to recruit a demographically diverse cohort of almost 11,900 9- and 10-year-old children from an initial 22 study sites. The analyzed sample included data from 8,524 typically developing child participants and their parents or caregivers. The primary outcomes and measures were subcortical brain structure, cognitive performance using the National Institutes of Health Toolbox, and geocoded risk of lead exposure. Children who lived in neighborhoods with greater risks of environmental lead exposure exhibited smaller volumes of the mid-anterior (partial correlation coefficient [rp] = -0.040), central (rp = -0.038), and mid-posterior corpus callosum (rp = -0.035). Smaller volumes of these three callosal regions were associated with poorer performance on cognitive tests measuring language and processing speed. The association of lead exposure risk with cognitive performance was partially mediated through callosal volume, particularly the mid-posterior corpus callosum. In contrast, neighborhood-level indicators of disadvantage were not associated with smaller volumes of these brain structures.

Conclusions: Environmental factors related to the risk of lead exposure may be associated with certain aspects of cognitive functioning via diminished subcortical brain structure, including the anterior splenium (i.e., mid-posterior corpus callosum).
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258469PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516269PMC
November 2021

Vertex-wise multivariate genome-wide association study identifies 780 unique genetic loci associated with cortical morphology.

Neuroimage 2021 Dec 21;244:118603. Epub 2021 Sep 21.

NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Building 48, Oslo University Hospital, Ullevål, PO Box 4956 Nydalen, Oslo 0424, Norway; Department of Neurosciences, University of California San Diego, La Jolla, CA 92037, USA; Department of Radiology, University of California San Diego, La Jolla, CA 92037, USA; Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA 92037, USA. Electronic address:

Brain morphology has been shown to be highly heritable, yet only a small portion of the heritability is explained by the genetic variants discovered so far. Here we extended the Multivariate Omnibus Statistical Test (MOSTest) and applied it to genome-wide association studies (GWAS) of vertex-wise structural magnetic resonance imaging (MRI) cortical measures from N=35,657 participants in the UK Biobank. We identified 695 loci for cortical surface area and 539 for cortical thickness, in total 780 unique genetic loci associated with cortical morphology robustly replicated in 8,060 children of mixed ethnicity from the Adolescent Brain Cognitive Development (ABCD) Study®. This reflects more than 8-fold increase in genetic discovery at no cost to generalizability compared to the commonly used univariate GWAS methods applied to region of interest (ROI) data. Functional follow up including gene-based analyses implicated 10% of all protein-coding genes and pointed towards pathways involved in neurogenesis and cell differentiation. Power analysis indicated that applying the MOSTest to vertex-wise structural MRI data triples the effective sample size compared to conventional univariate GWAS approaches. The large boost in power obtained with the vertex-wise MOSTest together with pronounced replication rates and highlighted biologically meaningful pathways underscores the advantage of multivariate approaches in the context of highly distributed polygenic architecture of the human brain.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118603DOI Listing
December 2021

Recalibrating expectations about effect size: A multi-method survey of effect sizes in the ABCD study.

PLoS One 2021 23;16(9):e0257535. Epub 2021 Sep 23.

Department of Psychiatry, University of Vermont, Burlington, VT, United States of America.

Effect sizes are commonly interpreted using heuristics established by Cohen (e.g., small: r = .1, medium r = .3, large r = .5), despite mounting evidence that these guidelines are mis-calibrated to the effects typically found in psychological research. This study's aims were to 1) describe the distribution of effect sizes across multiple instruments, 2) consider factors qualifying the effect size distribution, and 3) identify examples as benchmarks for various effect sizes. For aim one, effect size distributions were illustrated from a large, diverse sample of 9/10-year-old children. This was done by conducting Pearson's correlations among 161 variables representing constructs from all questionnaires and tasks from the Adolescent Brain and Cognitive Development Study® baseline data. To achieve aim two, factors qualifying this distribution were tested by comparing the distributions of effect size among various modifications of the aim one analyses. These modified analytic strategies included comparisons of effect size distributions for different types of variables, for analyses using statistical thresholds, and for analyses using several covariate strategies. In aim one analyses, the median in-sample effect size was .03, and values at the first and third quartiles were .01 and .07. In aim two analyses, effects were smaller for associations across instruments, content domains, and reporters, as well as when covarying for sociodemographic factors. Effect sizes were larger when thresholding for statistical significance. In analyses intended to mimic conditions used in "real-world" analysis of ABCD data, the median in-sample effect size was .05, and values at the first and third quartiles were .03 and .09. To achieve aim three, examples for varying effect sizes are reported from the ABCD dataset as benchmarks for future work in the dataset. In summary, this report finds that empirically determined effect sizes from a notably large dataset are smaller than would be expected based on existing heuristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257535PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460025PMC
November 2021

Effect sizes of associations between neuroimaging measures and affective symptoms: A meta-analysis.

Depress Anxiety 2021 Sep 13. Epub 2021 Sep 13.

Laureate Institute for Brain Research, Tulsa, Oklahoma, USA.

Background: The utility of brain-based biomarkers for psychiatric disorders hinges among other factors on their ability to explain a significant portion of the phenotypic variance. In particular, many small scale studies have been unable to arbitrate whether structural or functional magnetic resonance imaging has potential to be a biological marker for these disorders.

Methods: This study conducted a meta-analysis to examine the relationship between study power and published effect sizes for the relationship between affective symptoms and structural or functional magnetic resonance imaging measures. The current analyses are based on 821 brain-affective symptom association effect sizes derived from 120 publications, which employed a univariate region-of-interest approach.

Results: For self-assessed affective symptoms published brain imaging measures accounted for on average 8% (confidence interval: 1.6%-23%) of between-subject variation. This average effect size was based mostly on studies with small sample sizes, which have likely led to inflation of these effect size estimates.

Conclusions: These findings support the conclusion that brain imaging measures currently account for a smaller proportion of the interindividual variance in affective symptoms than has been previously reported. The current findings support the need for both large-sample clinical studies and new statistical and theoretical models to more robustly capture systematic variance of brain-affective symptom relationships.
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http://dx.doi.org/10.1002/da.23215DOI Listing
September 2021

Early Adolescent Substance Use Before and During the COVID-19 Pandemic: A Longitudinal Survey in the ABCD Study Cohort.

J Adolesc Health 2021 09;69(3):390-397

Department of Psychiatry, University of California, San Diego, La Jolla, California.

Purpose: Evaluate changes in early adolescent substance use during the coronavirus disease 2019 (COVID-19) pandemic using a prospective, longitudinal, nationwide cohort.

Methods: Participants were enrolled in the Adolescent Brain Cognitive Development Study. A total of 7,842 youth (mean age = 12.4 years, range = 10.5-14.6) at 21 study sites across the U.S. completed a three-wave assessment of substance use between May and August 2020. Youth reported whether they had used alcohol, nicotine, cannabis, or other substances in the past 30 days. Data were linked to prepandemic surveys that the same youth had completed in the years 2018-2020, before the advent of the COVID-19 pandemic.

Results: Past-30-day substance use remained stable in the 6 months since stay-at-home orders were first issued in U.S. states/counties; was primarily episodic (1-2 days in the past month); and was typically limited to a single substance. Using pretest/posttest and age-period designs, we found that compared to before the pandemic, fewer youth were using alcohol and more youth were using nicotine or misusing prescription drugs. During the pandemic, youth were more likely to use substances when they were more stressed by pandemic-related uncertainty; their family experienced material hardship; their parents used alcohol or drugs; or they experienced greater depression or anxiety. Neither engagement in social distancing nor worry about COVID-19 infection was associated with substance use. Several risk factors were stronger among older (vs. younger) adolescents.

Conclusions: Among youth in early adolescence, advent of the COVID-19 pandemic was associated with decreased use of alcohol and increased use of nicotine and misuse of prescription drugs.
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http://dx.doi.org/10.1016/j.jadohealth.2021.06.015DOI Listing
September 2021

Psychotic-like Experiences and Polygenic Liability in the Adolescent Brain Cognitive Development Study.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jul 13. Epub 2021 Jul 13.

Department of Psychological and Brain Sciences, Washington University, St. Louis, Missouri.

Background: Childhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms.

Methods: Adolescent Brain Cognitive Development Study baseline data from children with European ancestry (n = 4650, ages 9-10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models.

Results: Total and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔRs = 0.202%-0.660%; false discovery rate-corrected ps < .006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR = 0.120%-0.216%; false discovery rate-corrected ps < .03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated = 3.33%-32.22%).

Conclusions: Total and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.
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http://dx.doi.org/10.1016/j.bpsc.2021.06.012DOI Listing
July 2021

Polygenic risk for neuroticism moderates response to gains and losses in amygdala and caudate: Evidence from a clinical cohort.

J Affect Disord 2021 10 18;293:124-132. Epub 2021 Jun 18.

Laureate Institute for Brain Research, Tulsa, OK, USA.

Background: Neuroticism is a heritable trait that contributes to the vulnerability to depression. We used polygenic risk scores (PRS) to examine genetic vulnerability to neuroticism and its associations with reward/punishment processing in a clinical sample with mood, anxiety, and substance use disorders. It was hypothesized that higher PRS for neuroticism is associated with attenuated neural responses to reward/punishment.

Method: Four hundred sixty-nine participants were genotyped and their PRSs for neuroticism were computed. Associations between PRS for neuroticism and anticipatory processing of monetary incentives were examined using functional magnetic resonance imaging.

Results: Individuals with higher PRS for neuroticism showed less anticipatory activation in the left amygdala and caudate region to incentives regardless of incentive valence. Further, these individuals exhibited altered sensitivity to gain/loss processing in the right anterior insula. Higher PRSs for neuroticism were also associated with reduced processing of gains in the precuneus.

Limitations: The study population consisted of a transdiagnostic sample with dysfunctions in positive and negative valence processing. PRS for neuroticism may be correlated with current clinical symptoms due to the vulnerability to psychiatric disorders.

Conclusions: Greater genetic loading for neuroticism was associated with attenuated anticipatory responsiveness in reward/punishment processing with altered sensitivity to valences. Thus, a higher genetic risk for neuroticism may limit the degree to which positive and/or negative outcomes influence the current mood state, which may contribute to the development of positive and negative affective dysfunctions in individuals with mood, anxiety, and addictive disorders.
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http://dx.doi.org/10.1016/j.jad.2021.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411869PMC
October 2021

Meaningful associations in the adolescent brain cognitive development study.

Neuroimage 2021 10 18;239:118262. Epub 2021 Jun 18.

Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla, CA 92093, United States; Population Neuroscience and Genetics Lab, University of California, San Diego, La Jolla, CA 92093, United States. Electronic address:

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and children's health in the United States. A cohort of n = 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118262DOI Listing
October 2021

Cognitive Performance Trajectories Before and After Sleep Treatment Initiation in Middle-Aged and Older Adults: Results from the Health and Retirement Study.

J Gerontol A Biol Sci Med Sci 2021 Jun 11. Epub 2021 Jun 11.

Division of Pulmonary Medicine, Critical Care, and Sleep Medicine, University of California San Diego, La Jolla, CA.

Background: Sleep disturbances are associated with risk of cognitive decline but it is not clear if treating disturbed sleep mitigates decline. We examined differences in cognitive trajectories before and after sleep treatment initiation.

Methods: Data came from the 2006-2014 Health and Retirement Study. At each of five waves, participants were administered cognitive assessments and scores were summed. Participants also reported if, in prior two weeks, they had taken medications or used other treatments to improve sleep. Our sample (N=3,957) included individuals who at HRS 2006 were >50 years, had no cognitive impairment, reported no sleep treatment, and indicated experiencing sleep disturbance. We identified differences between those receiving vs. not receiving treatment in subsequent waves, and among those treated (N=1,247), compared cognitive trajectories before and after treatment.

Results: At baseline, those reporting sleep treatment at subsequent waves were more likely to be younger, female, Caucasian, to have more health conditions, to have higher BMI, and more depressive symptoms (all p's≤0.015). Decline in cognitive performance was mitigated in periods after sleep treatment vs. periods before (B=-0.20, 95% CI=-0.25, -0.15, p<0.001; vs., B=-0.26, 95% CI=-0.32, -0.20, p<0.001), and this same trend was seen for self-initiated and doctor-recommended treatments. Trends were driven by those with higher baseline cognitive performance-those with lower performance saw cognitive declines following sleep treatment.

Conclusions: In middle-aged and older adults with sleep disturbance, starting sleep treatment may slow cognitive decline. Future research should assess types, combinations, and timing of treatments most effective in improving cognitive health in later life.
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http://dx.doi.org/10.1093/gerona/glab164DOI Listing
June 2021

A large-scale investigation into the role of classical HLA loci in multiple types of severe infections, with a focus on overlaps with autoimmune and mental disorders.

J Transl Med 2021 05 31;19(1):230. Epub 2021 May 31.

iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.

Background: Infections are a major disease burden worldwide. While they are caused by external pathogens, host genetics also plays a part in susceptibility to infections. Past studies have reported diverse associations between human leukocyte antigen (HLA) alleles and infections, but many were limited by small sample sizes and/or focused on only one infection.

Methods: We performed an immunogenetic association study examining 13 categories of severe infection (bacterial, viral, central nervous system, gastrointestinal, genital, hepatitis, otitis, pregnancy-related, respiratory, sepsis, skin infection, urological and other infections), as well as a phenotype for having any infection, and seven classical HLA loci (HLA-A, B, C, DPB1, DQA1, DQB1 and DRB1). Additionally, we examined associations between infections and specific alleles highlighted in our previous studies of psychiatric disorders and autoimmune disease, as these conditions are known to be linked to infections.

Results: Associations between HLA loci and infections were generally not strong. Highlighted associations included associations between DQB1*0302 and DQB1*0604 and viral infections (P = 0.002835 and P = 0.014332, respectively), DQB1*0503 and sepsis (P = 0.006053), and DQA1*0301 with "other" infections (a category which includes infections not included in our main categories e.g. protozoan infections) (P = 0.000369). Some HLA alleles implicated in autoimmune diseases showed association with susceptibility to infections, but the latter associations were generally weaker, or with opposite trends (in the case of HLA-C alleles, but not with alleles of HLA class II genes). HLA alleles associated with psychiatric disorders did not show association with susceptibility to infections.

Conclusions: Our results suggest that classical HLA alleles do not play a large role in the etiology of severe infections. The discordant association trends with autoimmune disease for some alleles could contribute to mechanistic theories of disease etiology.
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http://dx.doi.org/10.1186/s12967-021-02888-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165335PMC
May 2021

Corrigendum to "Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders - Findings from a Danish population-based study" [Brain Behav. Immun. 91 (2021) 10-23].

Brain Behav Immun 2021 Aug 27;96:307-308. Epub 2021 May 27.

CORE-Copenhagen Research Centre for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

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http://dx.doi.org/10.1016/j.bbi.2021.05.019DOI Listing
August 2021

Breastfeeding Duration Is Associated With Domain-Specific Improvements in Cognitive Performance in 9-10-Year-Old Children.

Front Public Health 2021 26;9:657422. Epub 2021 Apr 26.

The Cognitive Neurophysiology Laboratory, The Del Monte Institute for Neuroscience, Department of Neuroscience, University of Rochester Medical Center, Rochester, NY, United States.

Significant immunological, physical and neurological benefits of breastfeeding in infancy are well-established, but to what extent these gains persist into later childhood remain uncertain. This study examines the association between breastfeeding duration and subsequent domain-specific cognitive performance in a diverse sample of 9-10-year-olds enrolled in the Adolescent Brain Cognitive Development (ABCD) Study®. The analyses included 9,116 children that attended baseline with their biological mother and had complete neurocognitive and breastfeeding data. Principal component analysis was conducted on data from an extensive battery of neurocognitive tests using varimax-rotation to extract a three-component model encompassing General Ability, Executive Functioning, and Memory. Propensity score weighting using generalized boosted modeling was applied to balance the distribution of observed covariates for children breastfed for 0, 1-6, 7-12, and more than 12 months. Propensity score-adjusted linear regression models revealed significant association between breastfeeding duration and performance on neurocognitive tests representing General Ability, but no evidence of a strong association with Executive Function or Memory. Benefits on General Ability ranged from a 0.109 (1-6 months) to 0.301 (>12 months) standardized beta coefficient difference compared to those not breastfed. Results indicate clear cognitive benefits of breastfeeding but that these do not generalize to all measured domains, with implications for public health policy as it pertains to nutrition during infancy.
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http://dx.doi.org/10.3389/fpubh.2021.657422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8109433PMC
May 2021

Rates of Incidental Findings in Brain Magnetic Resonance Imaging in Children.

JAMA Neurol 2021 May;78(5):578-587

Department of Psychiatry, University of Maryland, Baltimore.

Importance: Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings.

Objectives: To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended.

Design, Setting, And Participants: This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020.

Main Outcomes And Measures: Percentage of children with IFs in each category and prevalence of specific IFs.

Results: A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2 = 0.260; 95% CI, 0.135-0.387).

Conclusions And Relevance: Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.
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http://dx.doi.org/10.1001/jamaneurol.2021.0306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985817PMC
May 2021

Common genetic and clinical risk factors: association with fatal prostate cancer in the Cohort of Swedish Men.

Prostate Cancer Prostatic Dis 2021 09 15;24(3):845-851. Epub 2021 Mar 15.

Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.

Background: Clinical variables-age, family history, genetics-are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age at prostate cancer death. We evaluated if adding PHS to clinical variables improves associations with prostate cancer death.

Methods: Genotype/phenotype data were obtained from a nested case-control Cohort of Swedish Men (n = 3279; 2163 with prostate cancer, 278 prostate cancer deaths). PHS and clinical variables (family history, alcohol intake, smoking, heart disease, hypertension, diabetes, body mass index) were tested via univariable Cox proportional hazards models for association with age at prostate cancer death. Multivariable Cox models with/without PHS were compared with log-likelihood tests.

Results: Median age at last follow-up/prostate cancer death was 78.0 (IQR: 72.3-84.1) and 81.4 (75.4-86.3) years, respectively. On univariable analysis, PHS46 (HR 3.41 [95% CI 2.78-4.17]), family history (HR 1.72 [1.46-2.03]), alcohol (HR 1.74 [1.40-2.15]), diabetes (HR 0.53 [0.37-0.75]) were each associated with prostate cancer death. On multivariable analysis, PHS46 (HR 2.45 [1.99-2.97]), family history (HR 1.73 [1.48-2.03]), alcohol (HR 1.45 [1.19-1.76]), diabetes (HR 0.62 [0.42-0.90]) all remained associated with fatal disease. Including PHS46 or PHS166 improved multivariable models for fatal prostate cancer (p < 10).

Conclusions: PHS had the most robust association with fatal prostate cancer in a multivariable model with common risk factors, including family history. Adding PHS to clinical variables may improve prostate cancer risk stratification strategies.
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http://dx.doi.org/10.1038/s41391-021-00341-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387332PMC
September 2021

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Front Endocrinol (Lausanne) 2020 18;11:549928. Epub 2021 Feb 18.

Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.

Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.

Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.

Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.
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http://dx.doi.org/10.3389/fendo.2020.549928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930488PMC
May 2021

RAMIC: Design of a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of ramipril in patients with COVID-19.

Contemp Clin Trials 2021 04 22;103:106330. Epub 2021 Feb 22.

Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, United States of America; NAFLD Research Center, Department of Medicine, University of California San Diego, La Jolla, California, United States of America. Electronic address:

Background And Aims: Retrospective studies have shown that angiotensin-converting-enzyme (ACE) inhibitors are associated with a reduced risk of complications and mortality in persons with novel coronavirus disease 2019 (COVID-19). Thus, we aimed to examine the efficacy of ramipril, an ACE-inhibitor, in preventing ICU admission, mechanical ventilation and/or mortality while also minimizing the risk of transmission and use of personal protective equipment (PPE).

Methods: RAMIC is a multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial comparing the efficacy of treatment with ramipril 2.5 mg orally daily compared to placebo for 14 days. The study population includes adult patients with COVID-19 who were admitted to a hospital or assessed in an emergency department or ambulatory clinic. Key exclusion criteria include ICU admission or need for mechanical ventilation at screening, use of an ACE inhibitor or angiotensin-receptor-II blocker within 7 days, glomerular filtration rate < 40 mL/min or a systolic blood pressure (BP) < 100 mmHg or diastolic BP < 65 mmHg. Patients are randomized 2:1 to receive ramipril (2.5 mg) or placebo daily. Informed consent and study visits occur virtually to minimize the risk of SARS-CoV-2 transmission and preserve PPE. The primary composite endpoint of ICU admission, invasive mechanical ventilation and death are adjudicated virtually.

Conclusions: RAMIC is designed to assess the efficacy of treatment with ramipril for 14 days to decrease ICU admission, mechanical ventilator use and mortality in patients with COVID-19 and leverages virtual study visits and endpoint adjudication to mitigate risk of infection and to preserve PPE (ClinicalTrials.gov, NCT04366050).
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http://dx.doi.org/10.1016/j.cct.2021.106330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899027PMC
April 2021

Polygenic hazard score is associated with prostate cancer in multi-ethnic populations.

Nat Commun 2021 02 23;12(1):1236. Epub 2021 Feb 23.

Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS (PHS, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10). Comparing the 80/20 PHS percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
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http://dx.doi.org/10.1038/s41467-021-21287-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902617PMC
February 2021

Association of Heavy Drinking With Deviant Fiber Tract Development in Frontal Brain Systems in Adolescents.

JAMA Psychiatry 2021 Apr;78(4):407-415

Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California.

Importance: Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood.

Objective: To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents.

Design, Setting, And Participants: This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking.

Exposures: Self-reported alcohol consumption in the past year summarized by categorical drinking levels.

Main Outcomes And Measures: Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope.

Results: Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154 = -2.7, P = .008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156 = -0.21, 2-tailed P = .008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152 = 3.0, P = .004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence.

Conclusions And Relevance: This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.4064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774050PMC
April 2021

Screen media activity does not displace other recreational activities among 9-10 year-old youth: a cross-sectional ABCD study®.

BMC Public Health 2020 Nov 25;20(1):1783. Epub 2020 Nov 25.

Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK, 74136, USA.

Background: Screen media is among the most common recreational activities engaged in by children. The displacement hypothesis predicts that increased time spent on screen media activity (SMA) may be at the expense of engagement with other recreational activities, such as sport, music, and art. This study examined associations between non-educational SMA and recreational activity endorsement in 9-10-year-olds, when accounting for other individual (i.e., cognition, psychopathology), interpersonal (i.e., social environment), and sociodemographic characteristics.

Methods: Participants were 9254 youth from the Adolescent Brain Cognitive Development Study®. Latent factors reflecting SMA, cognition, psychopathology, and social environment were entered as independent variables into logistic mixed models. Sociodemographic covariates included age, sex, race/ethnicity, education, marital status, and household income. Outcome variables included any recreational activity endorsement (of 19 assessed), and specific sport (swimming, soccer, baseball) and hobby (music, art) endorsements.

Results: In unadjusted groupwise comparisons, youth who spent more time engaging with SMA were less likely to engage with other recreational activities (ps < .001). However, when variance in cognition, psychopathology, social environment, and sociodemographic covariates were accounted for, most forms of SMA were no longer significantly associated with recreational activity engagement (p > .05). Some marginal effects were observed: for every one SD increase in time spent on games and movies over more social forms of media, youth were at lower odds of engaging in recreational activities (adjusted odds ratio = 0·83, 95% CI 0·76-0·89). Likewise, greater general SMA was associated with lower odds of endorsing group-based sports, including soccer (0·93, 0·88-0·98) and baseball (0·92, 0·86-0·98). Model fit comparisons indicated that sociodemographic characteristics, particularly socio-economic status, explained more variance in rates of recreational activity engagement than SMA and other latent factors. Notably, youth from higher socio-economic families were up to 5·63 (3·83-8·29) times more likely to engage in recreational activities than youth from lower socio-economic backgrounds.

Conclusions: Results did not suggest that SMA largely displaces engagement in other recreational activities among 9-10-year-olds. Instead, socio-economic factors greatly contribute to rates of engagement. These findings are important considering recent shifts in time spent on SMA in childhood.
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http://dx.doi.org/10.1186/s12889-020-09894-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687784PMC
November 2020

Genome-wide association study identifies 16 genomic regions associated with circulating cytokines at birth.

PLoS Genet 2020 11 23;16(11):e1009163. Epub 2020 Nov 23.

The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.

Circulating inflammatory markers are essential to human health and disease, and they are often dysregulated or malfunctioning in cancers as well as in cardiovascular, metabolic, immunologic and neuropsychiatric disorders. However, the genetic contribution to the physiological variation of levels of circulating inflammatory markers is largely unknown. Here we report the results of a genome-wide genetic study of blood concentration of ten cytokines, including the hitherto unexplored calcium-binding protein (S100B). The study leverages a unique sample of neonatal blood spots from 9,459 Danish subjects from the iPSYCH initiative. We estimate the SNP-heritability of marker levels as ranging from essentially zero for Erythropoietin (EPO) up to 73% for S100B. We identify and replicate 16 associated genomic regions (p < 5 x 10-9), of which four are novel. We show that the associated variants map to enhancer elements, suggesting a possible transcriptional effect of genomic variants on the cytokine levels. The identification of the genetic architecture underlying the basic levels of cytokines is likely to prompt studies investigating the relationship between cytokines and complex disease. Our results also suggest that the genetic architecture of cytokines is stable from neonatal to adult life.
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http://dx.doi.org/10.1371/journal.pgen.1009163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721185PMC
November 2020

Brain Predictability toolbox: a Python library for neuroimaging-based machine learning.

Bioinformatics 2021 07;37(11):1637-1638

Department of Psychiatry and Complex Systems, University of Vermont, Burlington, VT 05401, USA.

Summary: Brain Predictability toolbox (BPt) represents a unified framework of machine learning (ML) tools designed to work with both tabulated data (e.g. brain derived, psychiatric, behavioral and physiological variables) and neuroimaging specific data (e.g. brain volumes and surfaces). This package is suitable for investigating a wide range of different neuroimaging-based ML questions, in particular, those queried from large human datasets.

Availability And Implementation: BPt has been developed as an open-source Python 3.6+ package hosted at https://github.com/sahahn/BPt under MIT License, with documentation provided at https://bpt.readthedocs.io/en/latest/, and continues to be actively developed. The project can be downloaded through the github link provided. A web GUI interface based on the same code is currently under development and can be set up through docker with instructions at https://github.com/sahahn/BPt_app.
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http://dx.doi.org/10.1093/bioinformatics/btaa974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485846PMC
July 2021
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