Structural differences in adolescent brains can predict alcohol misuse.
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ABSTRACT:
SUBMITTER: Rane RP
PROVIDER: S-EPMC9255959 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
Structural differences in adolescent brains can predict alcohol misuse.
Rane Roshan Prakash RP de Man Evert Ferdinand EF Kim JiHoon J Görgen Kai K Tschorn Mira M Rapp Michael A MA Banaschewski Tobias T Bokde Arun L W ALW Desrivieres Sylvane S Flor Herta H Grigis Antoine A Garavan Hugh H Gowland Penny A PA Brühl Rüdiger R Martinot Jean-Luc JL Martinot Marie-Laure Paillere MP Artiges Eric E Nees Frauke F Papadopoulos Orfanos Dimitri D Lemaitre Herve H Paus Tomas T Poustka Luise L Fröhner Juliane J Robinson Lauren L Smolka Michael N MN Winterer Jeanne J Whelan Robert R Schumann Gunter G Walter Henrik H Heinz Andreas A Ritter Kerstin K
eLife 20220526
Alcohol misuse during adolescence (AAM) has been associated with disruptive development of adolescent brains. In this longitudinal machine learning (ML) study, we could predict AAM significantly from brain structure (T1-weighted imaging and DTI) with accuracies of 73 -78% in the IMAGEN dataset (n∼1182). Our results not only show that structural differences in brain can predict AAM, but also suggests that such differences might precede AAM behavior in the data. We predicted 10 phenotypes of AAM a ...[more]
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Project description:Background and aimsResearch on adolescent predictors of later alcohol misuse is typically conducted on samples of singletons, and associations may be confounded by between-family differences. To address potential confounding, we applied a co-twin comparison design to evaluate whether differences between co-twins in a wide array of adolescent risk factors predicted differences in young adult alcohol misuse.DesignLongitudinal study in which associations between characteristics of the sample as adolescents were used to predict young adult alcohol misuse in individual-level analyses and co-twin comparisons.SettingFinland.ParticipantsA total of 3402 individuals (1435 complete twin pairs; 36% monozygotic; 57% female) from the FinnTwin12 study.MeasurementsThe young adult alcohol misuse outcome was a composite score of alcohol use and intoxication frequency. Adolescent predictors included factor scores representing academic performance, substance use, externalizing problems, internalizing problems, peer environment, physical health and relationship with parents; and single measures tapping alcohol expectancies, life events and pubertal development.FindingsIn individual-level analyses, individuals with higher adolescent substance use, externalizing problems, time with friends, peer deviance, sports involvement, sleeping difficulties, parental discipline, positive alcohol expectancies and difficulty of life events reported higher alcohol misuse in young adulthood (Ps < 0.019, R2 = 0.0003-0.0310%). Conversely, those with higher adolescent internalizing problems, parent-child relationship quality and time with parents reported lower alcohol misuse (Ps < 0021, R2 = 0.0018-0.0093%). The associations with adolescent substance use and alcohol expectancies remained significant in co-twin comparisons (Ps < 0.049, R2 = 0.0019-0.0314%). Further, academic performance emerged as a significant predictor, such that individuals with higher grades compared with their co-twin reported higher young adult alcohol misuse (Ps < 0.029, R2 = 0.0449-0.0533%).ConclusionsAdolescent substance use, positive alcohol expectancies and higher academic performance appear to be robust predictors of later alcohol misuse.
| S-EPMC7156309 | biostudies-literature
Project description:Considerable research efforts have attempted to identify genes associated with alcoholism among adults, yet few studies have examined adolescents. Identifying genes associated with alcohol misuse in youth is important given that the relative contribution of genetic and environmental influences on alcoholism varies across development. The purpose of this study was to examine the association between a polymorphism of the mu-opioid receptor gene (OPRM1) and alcohol misuse in a sample of youth and to test whether heightened sensitivity to the reinforcing effects of alcohol mediated this relationship.Adolescents (n = 187; mean age = 15.4 years; 47.6% female) were genotyped for A118G (rs1799971), a single-nucleotide polymorphism (SNP) of the OPRM1 gene, and assessed for alcohol use disorder (AUD) diagnoses and other psychopathology. Alcohol misuse was also measured continuously to maximize detection of drinking problems in youth. Drinking motives were used to capture the extent to which youth consumed alcohol to enhance positive affect.AUD groups differed significantly in terms of allelic distributions of the A118G SNP, such that 51.9% of youth with an AUD carried at least one copy of the G allele compared to 16.3% of non-AUD controls. Those who carried the G allele endorsed drinking to enhance positive affect more strongly than those who were homozygous for the A allele and drinking to enhance positive affect mediated the association between OPRM1 and alcohol-related problems.These data build on findings from adult studies and provide the first evidence that a polymorphism of the OPRM1 receptor gene is associated with the development of early-onset alcohol-related problems during adolescence, in part, by heightening sensitivity to the reinforcing effects of alcohol.
| S-EPMC3691683 | biostudies-literature
Project description:BackgroundWe sought to clarify the impact of adolescent alcohol misuse on adult physical health and subjective well-being. To do so, we investigated both the direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction and the indirect effects on these outcomes attributable to subsequent alcohol problems.MethodThe sample included 2733 twin pairs (32% monozygotic; 52% female) from the FinnTwin16 study. Adolescent alcohol misuse was a composite of frequency of drunkenness, frequency of alcohol use, and alcohol problems at ages 16, 17, and 18.5. The early midlife outcomes included somatic symptoms, self-rated health, and life satisfaction at age 34. The mediators examined as part of the indirect effect analyses included alcohol problems from the Rutgers Alcohol Problem Index at ages 24 and 34. Serial mediation and co-twin comparison models were applied and included covariates from adolescence and early midlife.ResultsThere were weak direct associations between adolescent alcohol misuse and early midlife physical health and life satisfaction. However, there was stronger evidence for indirect effects, whereby young adult and early midlife alcohol problems serially mediated the relationship between adolescent alcohol misuse and early midlife somatic symptoms (β = 0.03, 95% CI [0.03, 0.04]), self-rated health (β = -0.02, 95% CI [-0.03, -0.01]), and life satisfaction (β = -0.03, CI [-0.04, -0.02]). These serial mediation effects were robust in co-twin comparison analyses.ConclusionsThese results provide evidence that alcohol problems are a primary driver linking adolescent alcohol misuse and poor health outcomes across the lifespan.
| S-EPMC9509441 | biostudies-literature
Project description:The propensity to engage in risky behaviors including excessive alcohol consumption may impose increased medical, emotional, and psychosocial burdens. Personality and behavioral traits of individuals may contribute in part to the involvement in risky behaviors, and therefore the classification of one's traits may help identify those who are at risk for future onset of the addictive disorder and related behavioral issues such as alcohol misuse. Personality and behavioral characteristics including impulsivity, anger, reward sensitivity, and avoidance were assessed in a large sample of healthy young adults (n = 475). Participants also underwent diffusion tensor imaging for the analysis of structural brain networks. A data-driven clustering using personality and behavioral traits of the participants identified four subtypes. As compared with individuals clustered into the neutral type, individuals with a high level of impulsivity (A subtype) and those with high levels of reward sensitivity, impulsivity, anger, and avoidance (B subtype) showed significant associations with problem drinking. In contrast, individuals with high levels of impulsivity, anger, and avoidance but not reward sensitivity (C subtype) showed a pattern of social drinking that was similar to those of the neutral subtype. Furthermore, logistic regression analysis with ridge estimators was applied to demonstrate the neurobiological relevance for the identified subtypes according to distinct patterns of structural brain connectivity within the addiction circuitry [neutral vs. A subtype, the area under the receiver operator characteristic curve (AUC) = 0.74, 95% CI = 0.67-0.81; neutral vs. B subtype, AUC = 0.74, 95% CI = 0.66-0.82; neutral vs. C subtype, AUC = 0.77, 95% CI = 0.70-0.84]. The current findings enable the characterization of individuals according to subtypes based on personality and behavioral traits that are also corroborated by neuroimaging data and may provide a platform to better predict individual risks for addictive disorders.
| S-EPMC7062673 | biostudies-literature
Project description: Not available
| S-EPMC1410854 | biostudies-literature
Project description:ObjectivesThe objective was to assess the relationship between alcohol use and misuse and patient sex among emergency department (ED) patients by comparing self-reported estimates of quantity and frequency of alcohol use, estimated blood alcohol concentrations (eBACs) when typically drinking and during heavy episodic drinking (binging), and alcohol misuse severity, to understand sex differences in alcohol use and misuse for this population.MethodsThe authors surveyed a random sample of nonintoxicated, subcritically ill or injured, 18- to 64-year-old English- or Spanish-speaking patients on randomly selected dates and times at two EDs during July 2009 and August 2009. Participants self-administered a questionnaire about their self-reported alcohol use during a typical month within the past 12 months and the Alcohol Use Disorders Identification Test (AUDIT). Using the formulae by Matthews and Miller, sex-specific eBACs were calculated for participants according to their reported weight and the number of reported alcoholic drinks consumed on days when typically drinking and on days of heavy episodic (binge) drinking (five or more drinks/occasion for men, four or more drinks for women). Sex-specific alcohol misuse severity levels (low-risk, harmful, hazardous, and dependence) were calculated using AUDIT scores. Wilcoxon rank-sum and Pearson's chi-square tests were used to compare outcomes by sex. Negative binomial regression was used to assess the relationship between sex and the number of drinks consumed on a typical day, the number of days spent drinking and binging, and estimated AUDIT scores. Logistic regression was used to assess the outcome of the presence of binging according to sex. Multinomial logistic regression was used to compare by sex the percentage of days spent drinking and binging in 1 month, eBACs when typically drinking and when binging, and AUDIT at-risk drinking levels. Incidence rate ratios (IRRs) and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were estimated. All models were adjusted for patient demographic characteristics.ResultsOf the 513 participants, 52.1% were women, 55.8% were white non-Hispanic, and their median age was 34 years (interquartile range [IQR] = 25 to 46 years). Men reported greater mean alcohol consumption than women when typically drinking (4.3 vs. 3.3 drinks/day; p < 0.001) and during heavy episodic drinking (8.6 vs. 5.3 drinks/occasion; p < 0.001). Men spent more days drinking (IRR = 1.41, 95% CI = 1.19 to 1.65) and engaging in heavy episodic drinking (IRR = 1.68, 95% CI = 1.31 to 2.17) than women. Additionally, men were more likely to engage in heavy episodic drinking (AOR = 1.72, 95% CI = 1.16 to 2.56) than women. However, the mean eBACs for men and women were similar when typically drinking (0.05 vs. 0.06; p < 0.13) and during heavy episodic drinking (0.13 vs. 0.12; p < 0.13). Mean AUDIT scores were greater for men than women (7.5 vs. 5.3; p < 0.001), although alcohol misuse severity levels were similar between men and women (24.4% vs. 26.6% for hazardous, 2.8% vs. 2.2% for harmful, and 6.5% vs. 3.4% for dependence; p < 0.38).ConclusionsAlthough men drink more than women, women have similar eBACs with comparable levels of alcohol misuse. Women may benefit from recognizing that they are reaching similar levels of intoxication compared to men. Addressing these differences and possible health implications in future ED brief interventions may induce changes in problematic alcohol use among women.
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Project description:Adolescent sensitivity to alcohol is a predictor of continued alcohol use and misuse later in life. Thus, it is important to understand the many factors that can impact alcohol sensitivity. Data from our laboratory suggested that susceptibility to alcohol-associated contextual fear learning deficits varied among adolescent and adult mice from two mouse strains. To investigate the extent of genetic background's influences on adolescent learning after alcohol exposure, we examined how 9 inbred mouse strains differed in vulnerability to alcohol-induced contextual and cued fear conditioning deficits. We demonstrated significant strain- and sex-dependent effects of acute alcohol exposure on adolescent fear learning, with alcohol having most pronounced effects on contextual fear learning. Female adolescents were more susceptible than males to alcohol-induced impairments in contextual, but not cued, fear learning, independent of genetic background. Heritability for contextual and cued fear learning after alcohol exposure was estimated to be 31 % and 18 %, respectively. Learning data were compared to Blood Ethanol Concentrations (BEC) to assess whether strain differences in alcohol metabolism contributed to strain differences in learning after alcohol exposure. There were no clear relationships between BEC and learning outcomes, suggesting that strains differed in learning outcomes for reasons other than strain differences in alcohol metabolism. Genetic analyses revealed polymorphisms across strains in notable genes, such as Chrna7, a promising genetic candidate for susceptibility to alcohol-induced fear conditioning deficits. These results are the first to demonstrate the impact of genetic background on alcohol-associated fear learning deficits during adolescence and suggest that the mechanisms underlying this sensitivity are distinct from alcohol metabolism.
| S-EPMC10921434 | biostudies-literature
Project description:The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.
| S-EPMC6059181 | biostudies-literature
Project description:INTRODUCTION:Alcohol expectancies are important determinants and predictors of adolescent alcohol use. Research with African Americans has shown that the endorsement of positive alcohol expectancies differs from that of Whites during childhood and predicts different alcohol outcomes during young adulthood. However, limited research has explored racial differences in the relationship between expectancy endorsement and alcohol use in school-aged adolescents. The current study examines the effect of White or African American race on the relationship between positive alcohol expectancies and alcohol use. METHODS:Participants were 104 adolescents ages 12-18 who identified as either non-Hispanic White or non-Hispanic African American. Participants completed self-report measures of alcohol consumption and positive social alcohol expectancies. RESULTS:Preliminary analyses revealed no racial differences in alcohol expectancies or consumption. However, race moderated the relationship between alcohol expectancies and alcohol use such that more positive expectancies predicted alcohol use among White youth, but not African American youth. CONCLUSIONS:These results suggest that alcohol expectancies, which were thought to be important mediators of the relationship between social and personality factors and adolescent alcohol use may not be as impactful for African Americans. Future research should focus on identifying factors posing unique risk for alcohol consumption in this population.
| S-EPMC5608973 | biostudies-literature
Project description:Myelination defects in the central nervous system (CNS) are associated with various psychiatric disorders, including drug addiction. As these disorders are often observed in individuals prenatally exposed to cigarette smoking, we tested the hypothesis that such exposure impairs central myelination in adolescence, an important period of brain development and the peak age of onset of psychiatric disorders. Pregnant Sprague Dawley rats were treated with nicotine (3?mg?kg(-1) per day; gestational nicotine (GN)) or gestational saline via osmotic mini pumps from gestational days 4-18. Both male and female offsprings were killed on postnatal day 35 or 36, and three limbic brain regions, the prefrontal cortex (PFC), caudate putamen and nucleus accumbens, were removed for measurement of gene expression and determination of morphological changes using quantitative real-time PCR (qRT-PCR) array, western blotting and immunohistochemical staining. GN altered myelin gene expression at both the mRNA and protein levels, with striking sex differences. Aberrant expression of myelin-related transcription and trophic factors was seen in GN animals, which correlated highly with the alterations in the myelin gene expression. These correlations suggest that these factors contribute to GN-induced alterations in myelin gene expression and also indicate abnormal function of oligodendrocytes (OLGs), the myelin-producing cells in the CNS. It is unlikely that these changes are attributable solely to an alteration in the number of OLGs, as the cell number was changed only in the PFC of GN males. Together, our findings suggest that abnormal brain myelination underlies various psychiatric disorders and drug abuse associated with prenatal exposure to cigarette smoke.
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