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Background: Prenatal alcohol exposure (PAE) is linked to a variety of neurodevelopmental challenges, including social functioning (SF) and executive functioning (EF) deficits. These deficits present differently across developmental stages from preschool age to adolescence. Methods: The post hoc analyses described here were conducted on data from 83 preschool‐age children with PAE (early childhood group; ages 2.5 to 5.0) and 95 adolescents (49 with PAE, 46 controls; ages 8 to 16). Each child completed EF tasks as part of several prior studies. Parents completed social and communication inventories about their child's abilities. Thirty‐three participants from the early childhood group returned for a 4‐year follow‐up and completed both SF and EF measures. Results: Both the early childhood and adolescent groups with PAE showed deficits in SF and EF. There was a relationship between SF and EF within the adolescent PAE group that was not present in the adolescent control group or the early childhood PAE group. However, at the 4‐year follow‐up (Mage = 8.45), participants originally in the early childhood PAE group also demonstrated this relationship. Conclusions: These findings support previous research on EF/SF deficits in adolescents with PAE while also addressing a gap in the literature concerning early childhood research on this topic. Additionally, these findings suggest that the relationship between EF and SF deficits may strengthen throughout development. This line of research highlights potential sensitive periods for SF and EF training in children with PAE and suggests that fetal alcohol spectrum disorders programs consider targeting EF training as a component of social skill interventions. [ABSTRACT FROM AUTHOR]

Background: While many adolescents exhibit risky behavior, teenagers with a family history (FH+) of an alcohol use disorder (AUD) are at a heightened risk for earlier initiation of alcohol use, a more rapid escalation in frequency and quantity of alcohol consumption and developing a subsequent AUD in comparison with youth without such family history (FH−). Neuroanatomically, developmentally normative risk‐taking behavior parallels an imbalance between more protracted development of the prefrontal cortex (PFC) and earlier development of limbic regions. Magnetic resonance imaging (MRI)‐derived volumetric properties were obtained for these structures in FH+ and FH− adolescents. Methods: Forty‐two substance‐naïve adolescents (13‐ to 14‐year‐olds), stratified into FH+ (N = 19, 13 girls) and FH− (N = 23, 11 girls) age/handedness‐matched groups, completed MRI scanning at 3.0T, as well as cognitive and clinical testing. T1 images were processed using FreeSurfer to measure PFC and hippocampi/amygdalae subfields/nuclei volumes. Results: FH+ status was associated with larger hippocampal/amygdala volumes (p < 0.05), relative to FH− adolescents, with right amygdala results appearing to be driven by FH+ boys. Volumetric differences also were positively associated with family history density (p < 0.05) of having an AUD. Larger subfields/nuclei volumes were associated with higher anxiety levels and worse auditory verbal learning performance (p < 0.05). Conclusions: FH+ risk for AUD is detectable via neuromorphometric characteristics, which precede alcohol use onset and the potential onset of a later AUD, that are associated with emotional and cognitive measures. It is plausible that the development of limbic regions might be altered in FH+ youth, even prior to the onset of alcohol use, which could increase later risk. Thus, targeted preventative measures are warranted that serve to delay the onset of alcohol use in youth, particularly in those who are FH+ for an AUD. [ABSTRACT FROM AUTHOR]

The Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium has focused on the impact of adolescent binge drinking on brain development, particularly on effects that persist into adulthood. Adolescent binge drinking is common, and while many factors contribute to human brain development and alcohol use during adolescence, animal models are critical for understanding the specific consequences of alcohol exposure during this developmental period and the underlying mechanisms. Using adolescent intermittent ethanol (AIE) exposure models, NADIA investigators identified long‐lasting AIE‐induced changes in adult behavior that are consistent with observations in humans, such as increased alcohol drinking, increased anxiety (particularly social anxiety), increased impulsivity, reduced behavioral flexibility, impaired memory, disrupted sleep, and altered responses to alcohol. These behavioral changes are associated with multiple molecular, cellular, and physiological alterations in the brain that persist long after AIE exposure. At the molecular level, AIE results in long‐lasting changes in neuroimmune/trophic factor balance and epigenetic–microRNA (miRNA) signaling across glia and neurons. At the cellular level, AIE history is associated in adulthood with reduced expression of cholinergic, serotonergic, and dopaminergic neuron markers, attenuated cortical thickness, decreased neurogenesis, and altered dendritic spine and glial morphology. This constellation of molecular and cellular adaptations to AIE likely contributes to observed alterations in neurophysiology, measured by synaptic physiology, EEG patterns, and functional connectivity. Many of these AIE‐induced brain changes replicate findings seen in postmortem brains of humans with alcohol use disorder (AUD). NADIA researchers are now elucidating mechanisms of these adaptations. Emerging data demonstrate that exercise, antiinflammatory drugs, anticholinesterases, histone deacetylase inhibitors, and other pharmacological compounds are able to prevent (administered during AIE) and/or reverse (given after AIE) AIE‐induced pathology in adulthood. These studies support hypotheses that adolescent binge drinking increases risk of adult hazardous drinking and influences brain development, and may provide insight into novel therapeutic targets for AIE‐induced neuropathology and AUDs. [ABSTRACT FROM AUTHOR]

Although adolescents are developmentally distinct from adults, they often receive addiction treatment based on adult models. This is problematic because adolescents face significantly different conditions in addiction treatment, including distinct basic biological and neurodevelopmental stages, unique sociodevelopmental concerns, distinctive addiction trajectories, and, in turn, disparate treatment goals and outcomes. In sum, it can be difficult for even savvy clinicians to know how to approach addiction treatment with this important age group. In an effort to help clinicians and researchers consider substance use via a neurodevelopmental lens, we approached this review with 4 goals: (i) characterize the prevalence, and related health and safety implications of substance use within this age group; (ii) identify the nature of the adolescent brain, including characteristic features of this phase of neurodevelopment relevant to adolescent substance use treatment; (iii) provide an overview of current adolescent addiction interventions and avenues to improve clinical treatment and clinical research efforts for adolescents; and (iv) examine the intersection between the nature of the developing brain and adolescent substance use, and utilize that information to inform alternative routes and directions for substance use treatment in this critical age group. This review concludes by offering a novel neurodevelopmental model and framework to examine substance use interventions, along with a series of recommendations to optimize adolescent substance use treatment and clinical research. Although adolescents are developmentally distinct, they often receive addiction treatment based upon adult models. This is problematic because adolescents face disparate conditions in treatment, including distinct neurodevelopmental stages, sociodevelopmental concerns, addiction trajectories, treatment goals and outcomes. Yet, it can be difficult for clinicians to know how to approach addictions treatment with adolescents. In this review, we advance a novel neurodevelopmental model and framework for examining adolescent addictions interventions, and a series of recommendations to optimize adolescent treatment and clinical research. [ABSTRACT FROM AUTHOR]

Background Transitions into heavy alcohol use often already take place during adolescence and are likely to be both genetically and environmentally determined. Therefore, in a 6-wave longitudinal study, we examined the effects of DRD2 Taq1 A and OPRM1 A118 G genotypes and the interaction with parental rule-setting on different groups of adolescent drinkers. Methods Growth mixture modeling resulted in 3 distinct groups of adolescent drinkers: light drinkers ( n = 346), moderate drinkers ( n = 178), and heavy drinkers ( n = 72). Results Multinomial regression showed that moderate drinkers carried the OPRM1 G allele and received lower levels of parental rule-setting significantly more often than the light drinking group. No other significant main effects of DRD2, OPRM1, and rule-setting were found. The interaction between OPRM1 genotype and parental rule-setting significantly distinguished the heavy drinkers from the light ( p < 0.001) and moderate groups ( p = 0.055): Particularly, the alcohol use of OPRM1 G allele carriers was affected by parental rule-setting, while AA genotype carriers remained largely unaffected by parental rules. Conclusions Findings showed that different trajectories of adolescent drinking are preceded by a gene-parenting interaction. These results concur with Belsky's theory of plasticity (2009), as well as with Shanahan and Hofer's typology of a controlling and restricting gene-environment interaction (2005). [ABSTRACT FROM AUTHOR]

Background Disrupted sleep is a common complaint of individuals with alcohol use disorder and in abstinent alcoholics. Furthermore, among recovering alcoholics, poor sleep predicts relapse to drinking. Whether disrupted sleep in these populations results from prolonged alcohol use or precedes the onset of drinking is not known. The aim of this study was to examine the sleep electroencephalogram ( EEG) in alcohol-naïve, parental history positive ( PH+), and negative ( PH−) boys and girls. Methods All-night sleep EEG recordings in 2 longitudinal cohorts (child and teen) followed at 1.5 to 3 year intervals were analyzed. The child and teen participants were 9/10 and 15/16 years old at the initial assessment, respectively. Parental history status was classified by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM- IV) criteria applied to structured interviews ( DIS- IV) resulting in 14 PH− and 10 PH+ children and 14 PH− and 10 PH+ teens. Sleep data were visually scored in 30-second epochs using standard criteria. Power spectra were calculated for EEG derivations C3/ A2, C4/ A1, O2/ A1, O1/ A2 for nonrapid eye movement ( NREM) and rapid eye movement ( REM) sleep. Results We found no difference between PH+ and PH− individuals in either cohort for any visually scored sleep stage variable. Spectral power declined in both cohorts across assessments for NREM and REM sleep in all derivations and across frequencies independent of parental history status. With regard to parental history, NREM sleep EEG power was lower for the delta band in PH+ teens at both assessments for the central derivations. Furthermore, power in the sigma band for the right occipital derivation in both NREM and REM sleep was lower in PH+ children only at the initial assessment. Conclusions We found no gross signs of sleep disruption as a function of parental history. Modest differences in spectral EEG power between PH+ and PH− children and teens indicate that a marker of parental alcohol history may be detectable in teens at risk for problem drinking. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies suggest that initiation of alcohol drinking at an early age is associated with an increased risk of developing an alcohol use disorder later in life. Nevertheless, relatively few studies using animal models have investigated the relationship between age of onset of drinking and ethanol drinking patterns in adulthood. Besides age at drinking onset, other factors such as gender could also affect the pattern of development of alcohol consumption. In rodents, many studies have shown that females drink more than males. However, even if it is assumed that hormonal changes occurring at puberty could explain these differences, only one study performed in rats has investigated the emergence of sex-specific alcohol drinking patterns in adolescence and the transition from adolescence to adulthood. The aim of the present study was to compare the acquisition of voluntary alcohol consumption, relapse-like drinking (the Alcohol Deprivation Effect—ADE) and stress-induced alcohol drinking in male and female outbred mice that acquired alcohol consumption during adolescence or adulthood. Methods: Separate groups of naïve female and male WSC-1 mice aged ± 28 days (adolescents) or ±70 days (adults) were given ad libitum access to water and 6% ethanol solution for 8 weeks (1st to 8th week) before undergoing a 2-week deprivation phase (9th and 10th week). After the deprivation period, 2-bottle preference testing (ethanol vs. water) resumed for 3 weeks (11th to 13th). During the 13th week, all animals were subjected to restraint stress for 2 consecutive days. Results: Over the entire time course of the experiment, ethanol intake and preference increased in females (both adults and adolescents). Adolescent animals (both females and males) showed a transient increase in alcohol consumption and preference compared to adults. However, by the end of continuous alcohol exposure (when all mice were adults), ethanol intake was not affected by age at drinking onset. A deprivation phase was followed by a rise in ethanol intake (ADE) that was not affected by sex or age. Finally, stress did not alter alcohol self-administration either during or after its occurrence. Conclusions: Emergence of greater alcohol consumption in adult females does not seem to be limited to a specific developmental period ( i.e., puberty). Age of voluntary drinking onset (adolescence vs. adulthood) does not affect eventual alcohol intake in adult WSC-1 mice and does not modify the transient increase in ethanol consumption after alcohol deprivation. [ABSTRACT FROM AUTHOR]

Background: There has been considerable focus on the adolescent stage of development in the study of alcohol use and the etiology of alcohol-related problems. Because adolescence is a process of dynamic change rather than a discrete or static stage of development, it is important to consider ontogenetic changes in the response to ethanol within the adolescent time period. In rodents, levels of ethanol-induced motor impairment have been shown to increase from early to late adolescence. This study investigated associations between behavior following acute ethanol administration and age, rearing condition (mother-reared vs nursery-reared), and serotonin transporter (rh5-HTTLPR) genotype in a sample of alcohol-naïve adolescent rhesus macaques. Methods: Rhesus macaques ( n=97; 41 males, 56 females), ranging in age from 28 to 48 months, were administered intravenous (IV) doses of ethanol (2.2 g/kg for males, 2.0 g/kg for females) twice in 2 separate testing sessions. A saline/ethanol group ( n=16; 8 males, 6 females) was administered saline in 1 testing session and ethanol in the second session. Following each IV injection, subjects underwent a 30-minute general motor behavioral assessment. Behavior in the saline/ethanol group was compared between the saline and ethanol-testing sessions using analysis of variance. Behavioral data for the larger study sample were averaged between the 2 testing sessions and summarized using factor analysis. Rotated factor scores were used as dependent variables in multiple regression analyses to test for relationships between behavior and age, rearing condition, and rh5-HTTLPR genotype. Results: During the ethanol-testing session, behaviors indicative of motor impairment (stumbles, falls, sways, bumping the wall, and unsuccessful jumps) were frequently observed in the saline/ethanol group, while they did not occur under the saline-testing session. Factor analysis of behavior following ethanol administration in the larger study sample yielded 3 factors: Ataxia, Impaired Jumping Ability, and Stimulation. Significant negative correlations between age and Ataxia were found for both males and females. Females also exhibited positive correlations between age and Impaired Jumping Ability and age and Stimulation. No significant correlations were found with either rearing condition or rh5-HTTLPR genotype. Conclusions: These findings suggest that ontogenetic changes during adolescence in the behavioral response to ethanol differ between rodents and primates. Furthermore, sex differences in the behavioral response to ethanol appear to develop during adolescence. [ABSTRACT FROM AUTHOR]

Background Recent evidence indicates that adolescent and adult rats are differentially sensitive to many of the acute effects of ethanol. Little is known about the neurobehavioral consequences of repeated ethanol exposure during adolescence relative to adulthood. In the present study we examined the impact of repeated ethanol exposure during adolescence and adulthood on subsequent sensitivity to ethanol-induced motor impairments. Methods The tilting plane test was used to assess the impact of acute ethanol (3.0 g/kg) on motor coordination before (test 1), 2 days after (test 2), and 16 days after (test 3) a 20 day period of chronic-intermittent ethanol (CIE; 5.0 g/kg intraperitoneally every 48 hrs for 20 days) or isovolumetric chronic-intermittent saline (CIS) treatment in adolescent (postnatal (PD) 30) and adult (PD 70) rats. Results Adolescent subjects were less sensitive than adults to the effects of ethanol on motor coordination during test 1. Adolescent CIS-treated subjects exhibited an increase in sensitivity to ethanol-induced motor impairments that reached adult levels by test 2 (PD 51) and remained stable between test 2 and test 3 (PD 65). Adolescent CIE-treated subjects did not exhibit this age-related increase in sensitivity. In this group, the effects of acute ethanol remained unchanged across the three testing days. Adult CIE-treated subjects exhibited a small degree of tolerance between test 1 and test 2 (PD 91) that was no longer evident during test 3 (PD 105). In adult CIS-treated subjects, the effects of acute ethanol remained stable across the three testing days. Blood ethanol concentrations assessed during testing suggest that age-related changes in sensitivity to ethanol-induced motor impairments are not related to changes in ethanol metabolism. Conclusions The data suggest that CIE exposure during adolescence has a lasting impact on sensitivity to ethanol-induced motor impairments. This effect might stem from a disruption of normal developmental processes. [ABSTRACT FROM AUTHOR]

A characteristic of heritable alcoholism is an early onset of alcohol abuse, which may begin at or before the age of adolescence. The objective of the present study was to determine the ontogeny of alcohol drinking behavior before and during puberty in the selectively bred alcohol-preferring (P), alcohol-nonpreferring (NP), high alcohol drinking (HAD), and low alcohol drinking (LAD) lines of rats. In addition, the effects of postweaning housing conditions (single- or pair-housed) and initiation procedure (4 days forced ethanol or free-choice) were evaluated in male and female P rats. Results indicate that high alcohol drinking in P and HAD (replicate line 2) rats, as well as low alcohol drinking behavior in NP and LAD (replicate line 2) rats, is present as early as 3 to 4 weeks of age. Ethanol intakes in juvenile P and HAD rats reached levels of ∼4 to 5 g/kg/day by 38 to 41 days of age and were comparable with levels observed in adults. Neither housing conditions nor ethanol initiation procedure significantly altered the acquisition or magnitude of alcohol intake levels in juvenile male and female P rats. These results suggest that the neural substrates underlying divergent ethanol drinking behavior in P/NP and HAD/LAD lines of rats are present early in life. [ABSTRACT FROM AUTHOR]

Several personality needs have consistently been identified as placing adolescents at heightened risk for the relatively intensive use of alcohol and other drugs. At the same time, little is known about the natural history of personality change during adolescence as it relates to substance use behaviors. Yet, this question is of clear importance to our understanding of personality risk factors for substance use because personality needs appear less temporally stable during adolescence than later in the life span. In this study, we use prospective longitudinal data to investigate the relation of high-risk personality needs to substance use in two groups of adolescents: those who maintained a temporally stable personality need structure across 3 years and those who showed considerable changes in personality needs during the same time interval. Subjects were 12, 15, or 18 years old at the first test time and 15, 18, or 21 years old, respectively, at the second test time. For subjects of both sexes, only those who maintained a temporally stable, low-risk personality profile showed quite conservative substance use patterns across time compared with all others. Generalized personality changes were linked to more intensive substance use behaviors in males, especially among those who had high levels of risky personality needs at the first test time. In contrast, personality change, per se, did not appear as relevant to females' alcohol and other drug use behaviors until combined with information regarding their level of high-risk personality needs. The results are discussed in terms of their implications for prevention and future research. [ABSTRACT FROM AUTHOR]