Neurogenetic and multi‐omic sources of overlap among sensation seeking, alcohol consumption, and alcohol use disorder

Addiction Biology, Journal Year: 2024, Volume and Issue: 29(2)

Published: Jan. 29, 2024

Sensation seeking is bidirectionally associated with levels of alcohol consumption in both adult and adolescent samples, shared neurobiological genetic influences may part explain these associations. Links between sensation use disorder (AUD) primarily manifest via increased rather than through direct effects on increasing problems consequences. Here the overlap among seeking, consumption, AUD was examined using multivariate modelling approaches for genome-wide association study (GWAS) summary statistics conjunction neurobiologically informed analyses at multiple investigation. Meta-analytic genomic structural equation (GenomicSEM) were used to conduct GWAS AUD. Resulting downstream examine brain tissue enrichment heritability evidence (e.g., stratified GenomicSEM, RRHO, correlations neuroimaging phenotypes), identify regions likely contributing observed across traits H-MAGMA LAVA). Across approaches, results supported neurogenetic architecture characterised by overlapping genes expressed midbrain striatal tissues variants cortical surface area. Alcohol evidenced relation decreased frontocortical thickness. Finally, mediation models provided mediating associations This extends previous research examining critical sources multi-omic which underlie phenotypic

Language: Английский

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Impulsivity facets and substance use involvement: insights from genomic structural equation modeling

Psychological Medicine, Journal Year: 2025, Volume and Issue: 55

Published: Jan. 1, 2025

Abstract Background Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of involvement remains unclear. Methods We used genomic structural equation modeling genome-wide association studies ( N = 79,729–903,147) to examine latent genetic architecture nine traits seven (SU) SUD traits. Results found that SU factors were strongly genetically inter-correlated r G =0.77) their associations differed. Lack premeditation, negative positive urgency equally positively correlated both =.0.30–0.50) 0.38–0.46) factors; sensation seeking was more factor =0.27 versus =0.10); delay discounting =0.31 =0.21); lack perseverance only weakly =0.10). After controlling for correlation SU/SUD, we premeditation independently (β=0.42) (β=0.21); (β=0.48, β=0.33, respectively); (β=0.33, β=0.36, respectively). Conclusions Our findings show specific confer risk involvement, potential implications SUDs prevention treatment.

Language: Английский

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Neuroanatomical variability associated with early substance use initiation: Results from the ABCD Study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 8, 2024

Abstract The extent to which neuroanatomical variability associated with substance involvement reflects pre-existing risk and/or consequences of exposure remains poorly understood. In the Adolescent Brain Cognitive Development SM (ABCD®) Study, we identify associations between global and regional differences in brain structure early use initiation (i.e., occurring <15 years age; ns analytic =6,556-9,804), evidence that precede initiation. Neurodevelopmental may confer for involvement.

Language: Английский

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Neuroanatomical Variability and Substance Use Initiation in Late Childhood and Early Adolescence

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(12), P. e2452027 - e2452027

Published: Dec. 30, 2024

Importance The extent to which neuroanatomical variability associated with early substance involvement, is subsequent risk for use disorder development, reflects preexisting and/or consequences of exposure remains poorly understood. Objective To examine features initiation and what associations may reflect vulnerability. Design, Setting, Participants Cohort study using data from baseline through 3-year follow-up assessments the ongoing longitudinal Adolescent Brain Cognitive Development Study. Children aged 9 11 years at were recruited 22 sites across US between June 1, 2016, October 15, 2018. Data analyzed February September 2024. Exposures Substance (ie, age &amp;lt;15 years). Main Outcomes Measures Self-reported alcohol, nicotine, cannabis, other magnetic resonance imaging (MRI)–derived estimates brain structure global regional cortical volume, thickness, surface area, sulcal depth, subcortical volume). Covariates included family (eg, familial relationships), pregnancy prenatal substances), child sex pubertal status), MRI scanner model) variables. Results Among 9804 children (mean [SD] age, 9.9 [0.6] years; 5160 boys [52.6%]; 213 Asian [2.2%], 1474 Black [15.0%], 514 Hispanic/Latino [5.2%], 29 American Indian [0.3%], 10 Pacific Islander [0.1%], 7463 White [76.1%], 75 [0.7%]) nonmissing neuroimaging covariate data, 3460 (35.3%) reported before 15. Initiation any or alcohol was thinner cortex in prefrontal regions rostral middle frontal gyrus, β = −0.03; 95% CI, −0.02 −0.05; P 6.99 × −6 ) but thicker all lobes, larger globus pallidus hippocampal volumes, as well greater indices whole 0.05; 0.03 0.06; 2.80 −8 following Bonferroni false discovery rate multiple testing correction. Cannabis lower right caudate volume (β −0.01 .002). Post hoc examinations restricting postbaseline suggested that majority associations, including preceded initiation. Conclusions Relevance In this cohort children, addition putative neurotoxic effects exposure, predispositional initiating earlier life potential cascading implications development later problems.

Language: Английский

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Dual-systems models of the genetic architecture of impulsive personality traits: neurogenetic evidence of distinct but related factors

Psychological Medicine, Journal Year: 2023, Volume and Issue: 54(8), P. 1533 - 1543

Published: Nov. 29, 2023

Abstract Background Dual-systems models, positing an interaction between two distinct and competing systems (i.e. top-down self-control, bottom-up reward- or emotion-based drive), provide a parsimonious framework for investigating the interplay cortical subcortical brain regions relevant to impulsive personality traits (IPTs) their associations with psychopathology. Despite recent developments in multivariate analysis of genome-wide association studies (GWAS), molecular genetic investigations these models have not been conducted. Methods Using IPT GWAS, we conducted confirmatory genomic structural equation (GenomicSEM) empirically evaluate dual-systems architecture IPTs. Genetic correlations factors neuroimaging phenotypes (regional/structural volume, surface area, thickness) were estimated compared. Results GenomicSEM underscored important sources shared unique variance constructs. Specifically, model consisting sensation seeking lack self-control demonstrated but related influences ( r g = 0.60). correlation analyses provided evidence differential (e.g. negatively associated thickness, positively area). No significant observed phenotypes. Conclusions IPTs tested consistent study hypotheses, mixed no volumes). Findings demonstrate utility studying influences, also highlight potential limitations as interpreting endophenotypes

Language: Английский

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Genetic Risk for Alcohol Use Disorder in Relation to Individual Symptom Criteria: Do Polygenic Indices Provide Unique Information for Understanding Severity and Heterogeneity?

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Abstract Alcohol Use Disorder (AUD) is a heterogenous category with many unique configurations of symptoms. Previous investigations AUD heterogeneity using molecular genetics methods studied the association between genetic liability and individual symptoms at latent level or focusing on small number variants. Notably, these studies did not investigate potential severity differences in their analyses. Therefore, current study aimed to examine risk for symptom criteria by polygenic score (PRS) approach assess relative each test associates above beyond unidimensional construct. An PRS was created summary statistics obtained from published genome-wide (GWAS), Multiple Indicators Causes (MIMIC) models were employed effect overall as well after accounting this effect. The phenotypic highly correlated ( r = 0.78). Results MIMIC indicated that significantly predicted factor. Regression paths testing unique, direct effects symptoms, independent factor, significant. These results imply PRSs derived GWAS influence expression through single factor when measured level. Item-level are needed further parse heterogeneous allow more nuanced tests conclusions.

Language: Английский

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Binge drinking trajectories across adolescence and early adulthood: Associations with genetic influences for dual-systems impulsive personality traits, alcohol consumption, and alcohol use disorder

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 16, 2024

Abstract Binge drinking is a relatively common pattern of alcohol use among youth with normative frequency trajectories peaking in emerging and early adulthood. Frequent binge critical risk factor for not only the development disorders (AUDs) but also increased odds alcohol-related injury death, thus constitutes significant public health concern. Changes across are strongly associated changes impulsive personality traits (IPTs) which have been hypothesized as intermediate phenotypes genetic heavy AUD. The current study sought to examine extent longitudinal intoxication adolescence adulthood influences underlying dual-systems IPTs (i.e., top-down [lack self-control] bottom-up [sensation seeking urgency] constructs) alongside consumption Associations were tested using conditional latent growth curve polygenic score (PGS) models three independent samples ( N =10,554). Results suggested consistent associations all between sensation PGSs model intercepts higher at first measurement occasion) slopes steeper increases toward peak frequency). Urgency significantly or frequency. Collectively, these findings highlight role unique correlated IPT alcohol-specific factors emergence escalation during

Language: Английский

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Impulsivity Facets and Substance Use Involvement: Insights from Genomic Structural Equation Modeling

Published: Oct. 25, 2024

Abstract Background Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of involvement remains unclear. Methods We used genomic structural equation modeling genome-wide association studies (N=79,729-903,147) based on individuals European ancestry to examine latent genetic architecture behaviors. included GWAS data from nine traits seven (SU) SUD traits. Results found that SU factors were strongly genetically inter-correlated ( r G =0.77) their associations differed. Lack premeditation, negative positive urgency equally positively correlated both =.0.30-0.50) = 0.37-0.47) factors; sensation seeking was more factor =0.27 vs. =0.10); delay discounting =0.32 =0.21); lack perseverance only weakly =0.09). After controlling for correlation SU/SUD, we premeditation independently (β=0.39, β=0.28, respectively) (β=0.28, β=0.19, respectively); (β=0.46, (β=0.34, β=0.39, respectively). Conclusions Our findings show specific confer risk involvement, potential implications SUDs prevention treatment.

Language: Английский

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Genomic Structural Equation Modeling of Reward-Related Traits: Exploring the Genetic Factor Structure and its Relationship with Psychopathology

Psychiatry Research, Journal Year: 2024, Volume and Issue: 344, P. 116335 - 116335

Published: Dec. 19, 2024

Language: Английский

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