Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.

Background: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear.

Non-linear development of EEG coherence in adolescents and young adults shown by the analysis of neurophysiological trajectories and their covariance.

To contribute to the understanding of changes in the factors governing the development of neural connectivity, the developmental structure of EEG coherence in adolescents and young adults was analyzed using the means, variances, and covariances of high alpha frequency band coherence measures from a set of 27 coherence pairs obtained from a sample of 1426 participants from the COGA study with 5006 observations over ages 12 through 31. Means and covariances were calculated at 96 age centers by a LOESS method. In the current study, trajectories of covariance matrices considered as individual units were determined by tensorial analysis: calculation of Riemannian geodesic (non-Euclidean) distances between matrices and application of both linear and non-linear dimension reduction techniques to these distances.

Prediction of brain age in individuals with and at risk for alcohol use disorder using brain morphological features.

Brain age measures predicted from structural and functional brain features are increasingly being used to understand brain integrity, disorders, and health. While there is a vast literature showing aberrations in both structural and functional brain measures in individuals with and at risk for alcohol use disorder (AUD), few studies have investigated brain age in these groups. The current study examines brain age measures predicted using brain morphological features, such as cortical thickness and brain volume, in individuals with a lifetime diagnosis of AUD as well as in those at higher risk to develop AUD from families with multiple members affected with AUD (i.

Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons.

Genome-wide association studies (GWAS) of electroencephalographic endophenotypes for alcohol use disorder (AUD) has identified noncoding polymorphisms within the gene. encodes GIRK2, a subunit of a G-protein-coupled inwardly rectifying potassium channel that regulates neuronal excitability. We studied the effect of upregulating using an isogenic approach with human glutamatergic neurons derived from induced pluripotent stem cells (male and female donors).

COVID-19 pandemic stressors are associated with reported increases in frequency of drunkenness among individuals with a history of alcohol use disorder.

Some sources report increases in alcohol use have been observed since the start of the COVID-19 pandemic, particularly among women. Cross-sectional studies suggest that specific COVID-19-related stressful experiences (e.g.

Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features.

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems.

Examining associations between genetic and neural risk for externalizing behaviors in adolescence and early adulthood.

Background: Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers.

Methods: Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated.

Upregulated GIRK2 counteracts ethanol-induced changes in excitability & respiration in human neurons.

Unlabelled: Genome-wide association analysis (GWAS) of electroencephalographic endophenotypes for alcohol use disorder (AUD) has identified non-coding polymorphisms within the gene. encodes GIRK2, a subunit of a G protein-coupled inwardly-rectifying potassium channel that regulates neuronal excitability. How changes in GIRK2 affect human neuronal excitability and the response to repeated ethanol exposure is poorly understood.

Associations of parent-adolescent closeness with P3 amplitude, frontal theta, and binge drinking among offspring with high risk for alcohol use disorder.

Background: Parents impact their offspring's brain development, neurocognitive function, risk, and resilience for alcohol use disorder (AUD) via both genetic and socio-environmental factors. Individuals with AUD and their unaffected children manifest low parietal P3 amplitude and low frontal theta (FT) power, reflecting heritable neurocognitive deficits associated with AUD. Likewise, children who experience poor parenting tend to have atypical brain development and greater rates of alcohol problems.

Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons.

Synonymous and noncoding single nucleotide polymorphisms (SNPs) in the KCNJ6 gene, encoding G protein-gated inwardly rectifying potassium channel subunit 2 (GIRK2), have been linked with increased electroencephalographic frontal theta event-related oscillations (ERO) in subjects diagnosed with alcohol use disorder (AUD). To identify molecular and cellular mechanisms while retaining the appropriate genetic background, we generated induced excitatory glutamatergic neurons (iN) from iPSCs derived from four AUD-diagnosed subjects with KCNJ6 variants ("Affected: AF") and four control subjects without variants ("Unaffected: UN"). Neurons were analyzed for changes in gene expression, morphology, excitability and physiological properties.

Differentiating Individuals with and without Alcohol Use Disorder Using Resting-State fMRI Functional Connectivity of Reward Network, Neuropsychological Performance, and Impulsivity Measures.

Individuals with alcohol use disorder (AUD) may manifest an array of neural and behavioral abnormalities, including altered brain networks, impaired neurocognitive functioning, and heightened impulsivity. Using multidomain measures, the current study aimed to identify specific features that can differentiate individuals with AUD from healthy controls (CTL), utilizing a random forests (RF) classification model. Features included fMRI-based resting-state functional connectivity (rsFC) across the reward network, neuropsychological task performance, and behavioral impulsivity scores, collected from thirty abstinent adult males with prior history of AUD and thirty CTL individuals without a history of AUD.

Statistical Nonparametric fMRI Maps in the Analysis of Response Inhibition in Abstinent Individuals with History of Alcohol Use Disorder.

Inhibitory impairments may persist after abstinence in individuals with alcohol use disorder (AUD). Using traditional statistical parametric mapping (SPM) fMRI analysis, which requires data to satisfy parametric assumptions often difficult to satisfy in biophysical system as brain, studies have reported equivocal findings on brain areas responsible for response inhibition, and activation abnormalities during inhibition found in AUD persist after abstinence. Research is warranted using newer analysis approaches.

Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity.

Background And Purpose: The ENIGMA-EEG working group was established to enable large-scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain.

Methods: We summarize how we have performed our currently largest genome-wide association study of oscillatory brain activity in EEG recordings by meta-analyzing the results across five participating cohorts, resulting in the first genome-wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders.

Predicting alcohol use disorder remission: a longitudinal multimodal multi-featured machine learning approach.

Predictive models for recovering from alcohol use disorder (AUD) and identifying related predisposition biomarkers can have a tremendous impact on addiction treatment outcomes and cost reduction. Our sample (N = 1376) included individuals of European (EA) and African (AA) ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA) who were initially assessed as having AUD (DSM-5) and reassessed years later as either having AUD or in remission. To predict this difference in AUD recovery status, we analyzed the initial data using multimodal, multi-features machine learning applications including EEG source-level functional brain connectivity, Polygenic Risk Scores (PRS), medications, and demographic information.

A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior.

Aberrant connectivity of large-scale brain networks has been observed among individuals with alcohol use disorders (AUDs) as well as in those at risk, suggesting deficits in neural communication between brain regions in the liability to develop AUD. Electroencephalographical (EEG) coherence, which measures the degree of synchrony between brain regions, may be a useful measure of connectivity patterns in neural networks for studying the genetics of AUD. In 8810 individuals (6644 of European and 2166 of African ancestry) from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Multi-Trait Analyses of genome-wide association studies (MTAG) on parietal resting-state theta (3-7 Hz) EEG coherence, which previously have been associated with AUD.

Random Forest Classification of Alcohol Use Disorder Using EEG Source Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures.

Individuals with alcohol use disorder (AUD) manifest a variety of impairments that can be attributed to alterations in specific brain networks. The current study aims to identify features of EEG-based functional connectivity, neuropsychological performance, and impulsivity that can classify individuals with AUD (N = 30) from unaffected controls (CTL, N = 30) using random forest classification. The features included were: (i) EEG source functional connectivity (FC) of the default mode network (DMN) derived using eLORETA algorithm, (ii) neuropsychological scores from the Tower of London test (TOLT) and the visual span test (VST), and (iii) impulsivity factors from the Barratt impulsiveness scale (BIS).

Random Forest Classification of Alcohol Use Disorder Using fMRI Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures.

Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can classify adult males with AUD ( = 30) from healthy controls (CTL, = 30) using the Random Forest (RF) classification method. The predictor variables were: (i) fMRI-based within-network functional connectivity (FC) of the Default Mode Network (DMN), (ii) neuropsychological scores from the Tower of London Test (TOLT), and the Visual Span Test (VST), and (iii) impulsivity factors from the Barratt Impulsiveness Scale (BIS).

Density and Dichotomous Family History Measures of Alcohol Use Disorder as Predictors of Behavioral and Neural Phenotypes: A Comparative Study Across Gender and Race/Ethnicity.

Background: Family history (FH) is an important risk factor for the development of alcohol use disorder (AUD). A variety of dichotomous and density measures of FH have been used to predict alcohol outcomes; yet, a systematic comparison of these FH measures is lacking. We compared 4 density and 4 commonly used dichotomous FH measures and examined variations by gender and race/ethnicity in their associations with age of onset of regular drinking, parietal P3 amplitude to visual target, and likelihood of developing AUD.

Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples.

Background: Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

Methods: We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood.

Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (-threshold < 0.

Predicting risk for Alcohol Use Disorder using longitudinal data with multimodal biomarkers and family history: a machine learning study.

Predictive models have succeeded in distinguishing between individuals with Alcohol use Disorder (AUD) and controls. However, predictive models identifying who is prone to develop AUD and the biomarkers indicating a predisposition to AUD are still unclear. Our sample (n = 656) included offspring and non-offspring of European American (EA) and African American (AA) ancestry from the Collaborative Study of the Genetics of Alcoholism (COGA) who were recruited as early as age 12 and were unaffected at first assessment and reassessed years later as AUD (DSM-5) (n = 328) or unaffected (n = 328).

Lower Prefrontal and Hippocampal Volume and Diffusion Tensor Imaging Differences Reflect Structural and Functional Abnormalities in Abstinent Individuals with Alcohol Use Disorder.

Background: Alcohol use disorder (AUD) is known to have adverse effects on brain structure and function. Multimodal assessments investigating volumetric, diffusion, and cognitive characteristics may facilitate understanding of the consequences of long-term alcohol use on brain circuitry, their structural impairment patterns, and their impact on cognitive function in AUD.

Methods: Voxel- and surface-based volumetric estimations, diffusion tensor imaging (DTI), and neuropsychological tests were performed on 60 individuals: 30 abstinent individuals with AUD (DSM-IV) and 30 healthy controls.