Trait stability of measures is an essential requirement for individual differences research. Functional MRI has been increasingly used in studies that rely on the assumption of trait stability, such as attempts to relate task related brain activation to individual differences in behavior and psychopathology. However, recent research using adult samples has questioned the trait stability of task-fMRI measures, as assessed by test-retest correlations. To date, little is known about trait stability of task fMRI in children. Here, we examined within-session reliability and long-term stability of individual differences in task-fMRI measures using fMRI measures of brain activation provided by the adolescent brain cognitive development (ABCD) Study Release v4.0 as an individual's average regional activity, using its tasks focused on reward processing, response inhibition, and working memory. We also evaluated the effects of factors potentially affecting reliability and stability. Reliability and stability (quantified as the ratio of non-scanner related stable variance to all variances) was poor in virtually all brain regions, with an average value of 0.088 and 0.072 for short term (within-session) reliability and long-term (between-session) stability, respectively, in regions of interest (ROIs) historically-recruited by the tasks. Only one reliability or stability value in ROIs exceeded the 'poor' cut-off of 0.4, and in fact rarely exceeded 0.2 (only 4.9%). Motion had a pronounced effect on estimated reliability/stability, with the lowest motion quartile of participants having a mean reliability/stability 2.5 times higher (albeit still 'poor') than the highest motion quartile. Poor reliability and stability of task-fMRI, particularly in children, diminishes potential utility of fMRI data due to a drastic reduction of effect sizes and, consequently, statistical power for the detection of brain-behavior associations. This essential issue urgently needs to be addressed through optimization of task design, scanning parameters, data acquisition protocols, preprocessing pipelines, and data denoising methods.

Background

Survival analysis was used to explore the addition of a single nucleotide polymorphism (SNP) and covariates (sex, interview age, and ancestry) on a previously published model's ability to predict onset of drinking. A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking.

Methods

A subsample of 674 adolescents (ages 14-17) participating in the Collaborative Study on the Genetics of Alcoholism (COGA) was examined using a previously derived Cox proportional hazards model containing: 1) number of non-drinking related conduct disorder (CD) symptoms, 2) membership in a high-risk alcohol-dependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach Youth Self Report (YSR) externalizing score, and 5) YSR social problems score. The above covariates along with the SNP variant of GABRA2, rs279871, were added to this model. Five new prototype models were examined. The most parsimonious model was chosen based on likelihood ratio tests and model fit statistics.

Results

The final model contained four of the five original predictors (YSR social problems score was no longer significant and hence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (two copies of the high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype were more likely to begin drinking than those without this genotype.

Conclusions

The joint effect of the gene (rs279871 TT genotype) and environment (MBFD) on adolescent alcohol initiation is additive, but not interactive, after controlling for behavior problems (CD and YSR externalizing score). This suggests that the impact of the high-risk TT genotype on the onset of drinking is affected by controlling for peer drinking and does not include genotype-by-environment interactions.

The Adolescent Brain Cognitive Development (ABCD)^SM study aims to retain a demographically diverse sample of youth and one parent across 21 sites throughout its 10-year protocol while minimizing selective (systematic) attrition. To evaluate the effectiveness of these efforts, the ABCD Retention Workgroup (RW) has employed a data-driven approach to examine, track, and intervene via three key metrics: (1) which youth completed visits late; (2) which youth missed visits; and (3) which youth withdrew from the study. The RW actively examines demographic (race, education level, family income) and site factors (visit satisfaction, distance from site, and enrollment in ancillary studies) to strategize efforts that will minimize disengagement and loss of participating youth and parents. Data showed that the most robust primary correlates of late visits were distance from study site, race, and parental education level. Race, lower parental education level, parental employment status, and lower family income were associated with higher odds of missed visits, while being enrolled in one of the ancillary studies was associated with lower odds of missed visits. Additionally, parents who were primary Spanish speakers withdrew at slightly higher rates. These findings provide insight into future targets for proactive retention efforts by the ABCD RW.

Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9-11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen's d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development.

Background

Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. Event-related oscillations (EROs) have been used to effectively measure brain (dys)function during cognitive tasks in individuals with alcoholism and related disorders and in those at risk to develop these disorders. The current study examines ERO theta power during reward processing as well as impulsivity in adolescent and young adult subjects at high risk for alcoholism.

Methods

EROs were recorded during a monetary gambling task (MGT) in 12-25 years old participants (N = 1821; males = 48%) from high risk alcoholic families (HR, N = 1534) and comparison low risk community families (LR, N = 287) from the Collaborative Study on the Genetics of Alcoholism (COGA). Impulsivity scores and prevalence of externalizing diagnoses were also compared between LR and HR groups.

Results

HR offspring showed lower theta power and decreased current source density (CSD) activity than LR offspring during loss and gain conditions. Younger males had higher theta power than younger females in both groups, while the older HR females showed more theta power than older HR males. Younger subjects showed higher theta power than older subjects in each comparison. Differences in topography (i.e., frontalization) between groups were also observed. Further, HR subjects across gender had higher impulsivity scores and increased prevalence of externalizing disorders compared to LR subjects.

Conclusions

As theta power during reward processing is found to be lower not only in alcoholics, but also in HR subjects, it is proposed that reduced reward-related theta power, in addition to impulsivity and externalizing features, may be related in a predisposition to develop alcoholism and related disorders.

Background

Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. Event-related oscillations (EROs) have been used to effectively measure brain (dys)function during cognitive tasks in individuals with alcoholism and related disorders and in those at risk to develop these disorders. The current study examines ERO theta power during reward processing as well as impulsivity in adolescent and young adult subjects at high risk for alcoholism.

Methods

EROs were recorded during a monetary gambling task (MGT) in 12-25 years old participants (N = 1821; males = 48%) from high risk alcoholic families (HR, N = 1534) and comparison low risk community families (LR, N = 287) from the Collaborative Study on the Genetics of Alcoholism (COGA). Impulsivity scores and prevalence of externalizing diagnoses were also compared between LR and HR groups.

Results

HR offspring showed lower theta power and decreased current source density (CSD) activity than LR offspring during loss and gain conditions. Younger males had higher theta power than younger females in both groups, while the older HR females showed more theta power than older HR males. Younger subjects showed higher theta power than older subjects in each comparison. Differences in topography (i.e., frontalization) between groups were also observed. Further, HR subjects across gender had higher impulsivity scores and increased prevalence of externalizing disorders compared to LR subjects.

Conclusions

As theta power during reward processing is found to be lower not only in alcoholics, but also in HR subjects, it is proposed that reduced reward-related theta power, in addition to impulsivity and externalizing features, may be related in a predisposition to develop alcoholism and related disorders.

Background

Survival analysis was used to explore the addition of a single nucleotide polymorphism (SNP) and covariates (sex, interview age, and ancestry) on a previously published model's ability to predict onset of drinking. A SNP variant of rs279871, in the chromosome 4 gene encoding gamma-aminobutyric acid receptor (GABRA2), was selected due to its associations with alcoholism in young adults and with behaviors that increased risk for early drinking.

Methods

A subsample of 674 adolescents (ages 14-17) participating in the Collaborative Study on the Genetics of Alcoholism (COGA) was examined using a previously derived Cox proportional hazards model containing: 1) number of non-drinking related conduct disorder (CD) symptoms, 2) membership in a high-risk alcohol-dependent (AD) family, 3) most best friends drank (MBFD), 4) Achenbach Youth Self Report (YSR) externalizing score, and 5) YSR social problems score. The above covariates along with the SNP variant of GABRA2, rs279871, were added to this model. Five new prototype models were examined. The most parsimonious model was chosen based on likelihood ratio tests and model fit statistics.

Results

The final model contained four of the five original predictors (YSR social problems score was no longer significant and hence dropped from subsequent models), the three covariates, and a recessive GABRA2 rs279871 TT genotype (two copies of the high-risk allele containing thymine). The model indicated that adolescents with the high-risk TT genotype were more likely to begin drinking than those without this genotype.

Conclusions

The joint effect of the gene (rs279871 TT genotype) and environment (MBFD) on adolescent alcohol initiation is additive, but not interactive, after controlling for behavior problems (CD and YSR externalizing score). This suggests that the impact of the high-risk TT genotype on the onset of drinking is affected by controlling for peer drinking and does not include genotype-by-environment interactions.

Background

Alcohol problems reflect both environmental and genetic characteristics that often operate through endophenotypes like low levels of response (low LRs) to alcohol and higher impulsivity. Relationships of these preexisting characteristics to alcohol problems have been studied, but few analyses have included both low LR and impulsivity in the same model.

Methods

We extracted prospective data from 1,028 participants in the Prospective Youth Sample of the Collaborative Study on the Genetics of Alcoholism (COGA). At Time 1 (age 18), these drinking but non-alcohol-dependent males and females completed the Barratt Impulsivity Scale and the Self-Report of the Effects of Alcohol questionnaire regarding drinks required for effects the first 5 times of drinking (SRE5-LR). Two years later, they reported perceived drinking patterns of peers (PEER), their own alcohol expectancies (EXPECT), and their drinking to cope with stress (COPE). Subsequently, at Time 3, participants reported numbers of up to 11 DSM-IV alcohol criterion items experienced in the 2 years since Time 2 (ALC PROBS). Data were analyzed using structural equation modeling (SEM).

Results

In the SEM, Baseline SRE5-LR and impulsivity were weakly related and did not interact in predicting later ALC PROBS. LR was directly linked to Time 3 ALC PROBS and to PEER, but had no direct path to EXPECT, with partial mediation to ALC PROBS through PEER to EXPECT and via COPE. Impulsivity did not relate directly to ALC PROBS or PEER, but was directly related to EXPECT and COPE, with effects on ALC PROBS also operating through EXPECT and COPE.

Conclusions

Low LRs and impulsivity related to Time 3 ALC PROBS through somewhat different paths. Education- and counseling-based approaches to mitigate future alcohol problems may benefit from emphasizing different potential mediators of adverse alcohol outcomes for youth with low LRs versus those with high impulsivity or both characteristics.

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. Conversely, positive parenting can be protective and critical for normative development of self-regulation, neurocognitive functioning and the neurobiological systems subserving them. Yet, the role of positive parenting in resiliency toward AUD is understudied and its association with neurocognitive functioning and behavioral vulnerability to AUD among high-risk offspring is less known. Using data from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1256, mean age [SD] = 19.25 [1.88]), we investigated the associations of closeness with mother and father during adolescence with offspring P3 amplitude, FT power, and binge drinking among high-risk offspring.

Methods

Self-reported closeness with mother and father between ages 12 and 17 and binge drinking were assessed using the Semi-Structured Assessment for the Genetics of Alcoholism. P3 amplitude and FT power were assessed in response to target stimuli using a Visual Oddball Task.

Results

Multivariate multiple regression analyses showed that closeness with father was associated with larger P3 amplitude (p = 0.002) and higher FT power (p = 0.01). Closeness with mother was associated with less binge drinking (p = 0.003). Among male offspring, closeness with father was associated with larger P3 amplitude, but among female offspring, closeness with mother was associated with less binge drinking. These associations remained statistically significant with father's and mothers' AUD symptoms, socioeconomic status, and offspring impulsivity in the model.

Conclusions

Among high-risk offspring, closeness with parents during adolescence may promote resilience for developing AUD and related neurocognitive deficits albeit with important sex differences.

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.