Cognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here, we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N = 10 145) of 9-11-year-old children from the Adolescent Brain and Cognitive DevelopmentSM (ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly, not controlling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.

Background: Epidemiological and molecular findings suggest a relationship between Alzheimer's disease (AD) and dyslipidemia, although the nature of this association is not well understood. Results: Using linear mixed effects models, we investigated the relationship between CSF levels of heart fatty acid binding protein (HFABP), a lipid binding protein involved with fatty acid metabolism and lipid transport, amyloid-β (Aβ), phospho-tau, and longitudinal MRI-based measures of brain atrophy among 295 non-demented and demented older individuals. Across all participants, we found a significant association of CSF HFABP with longitudinal atrophy of the entorhinal cortex and other AD-vulnerable neuroanatomic regions. However, we found that the relationship between CSF HABP and brain atrophy was significant only among those with low CSF Aβ1-42and occurred irrespective of phospho-tau181pstatus. Conclusions: Our findings indicate that Aβ-associated volume loss occurs in the presence of elevated HFABP irrespective of phospho-tau. This implicates a potentially important role for fatty acid binding proteins in Alzheimer's disease neurodegeneration. © 2013 Desikan et al.; licensee BioMed Central Ltd.

Adolescent screen usage is ubiquitous and influences development and behavior. Longitudinal screen usage data coupled with psychometrically valid constructs of problematic behaviors can provide insights into these relationships. We describe methods by which the screen usage questionnaire was developed in the Adolescent Brain Cognitive Development (ABCD) Study, demonstrate longitudinal changes in screen usage via child report and describe data harmonization baseline-year 2. We further include psychometric analyses of adapted social media and video game addiction scales completed by youth. Nearly 12,000 children ages 9-10 years at baseline and their parents were included in the analyses. The social media addiction questionnaire (SMAQ) showed similar factor structure and item loadings across sex and race/ethnicities, but that item intercepts varied across both sex and race/ethnicity. The videogame addiction questionnaire (VGAQ) demonstrated the same configural, metric and scalar invariance across racial and ethnic groups, however differed across sex. Video gaming and online social activity increased over ages 9/10-11/12 (p's < 0.001). Compared with boys, girls engaged in greater social media use (p < .001) and demonstrated higher ratings on the SMAQ (p < .001). Compared with girls, boys played more video games (p < .001) and demonstrated higher ratings on the VGAQ (p < .001). Time spent playing video games increased more steeply for boys than girls from age 9/10-11/12 years (p < .001). Black youth demonstrated significantly higher SMAQ and VGAQ scores compared to all other racial/ethnic groups. These data show the importance of considering different screen modalities beyond total screen use and point towards clear demographic differences in use patterns. With these comprehensive data, ABCD is poised to address critical questions about screen usage changes across adolescence.

BACKGROUND:Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN:We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION:This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION:The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21,856) and multiple sclerosis (MS) (n=43,879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16,731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility.

The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan-Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose-response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10−10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10−7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD's common inherited influences.

The main objective of the multi-site Pediatric Imaging, Neurocognition, and Genetics (PING) study was to create a large repository of standardized measurements of behavioral and imaging phenotypes accompanied by whole genome genotyping acquired from typically-developing children varying widely in age (3 to 20 years). This cross-sectional study produced sharable data from 1493 children, and these data have been described in several publications focusing on brain and cognitive development. Researchers may gain access to these data by applying for an account on the PING portal and filing a data use agreement. Here we describe the recruiting and screening of the children and give a brief overview of the assessments performed, the imaging methods applied, the genetic data produced, and the numbers of cases for whom different data types are available. We also cite sources of more detailed information about the methods and data. Finally we describe the procedures for accessing the data and for using the PING data exploration portal.

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10 -7). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.