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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. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; N = 2851) and African ancestry (AA; N = 1402). Analyses were also stratified by age (adolescents, age 12-17 and young adults, age 18-32). RESULTS: The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors. CONCLUSIONS: Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.
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Alcoholismo , Adulto Joven , Humanos , Adolescente , Adulto , Niño , Alcoholismo/genética , Trastorno de Personalidad Antisocial/genética , Factores de RiesgoRESUMEN
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. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk. METHODS: Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones. RESULTS: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20). CONCLUSIONS: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
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Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.
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Alcoholismo , Trastornos Relacionados con Sustancias , Tabaquismo , Humanos , Adulto Joven , Adulto , Tabaquismo/genética , Alcoholismo/genética , Trastornos Relacionados con Sustancias/genética , Factores de Riesgo , Consumo de Bebidas AlcohólicasRESUMEN
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.
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Encéfalo , Imagen por Resonancia Magnética , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Mapeo Encefálico/métodos , Niño , Humanos , Individualidad , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los ResultadosRESUMEN
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). Machine learning analysis was performed for 220 EEG measures, 149 alcohol-related single nucleotide polymorphisms (SNPs) from a recent large Genome-wide Association Study (GWAS) of alcohol use/misuse and two family history (mother DSM-5 AUD and father DSM-5 AUD) features using supervised, Linear Support Vector Machine (SVM) classifier to test which features assessed before developing AUD predict those who go on to develop AUD. Age, gender, and ancestry stratified analyses were performed. Results indicate significant and higher accuracy rates for the AA compared with the EA prediction models and a higher model accuracy trend among females compared with males for both ancestries. Combined EEG and SNP features model outperformed models based on only EEG features or only SNP features for both EA and AA samples. This multidimensional superiority was confirmed in a follow-up analysis in the AA age groups (12-15, 16-19, 20-30) and EA age group (16-19). In both ancestry samples, the youngest age group achieved higher accuracy score than the two other older age groups. Maternal AUD increased the model's accuracy in both ancestries' samples. Several discriminative EEG measures and SNPs features were identified, including lower posterior gamma, higher slow wave connectivity (delta, theta, alpha), higher frontal gamma ratio, higher beta correlation in the parietal area, and 5 SNPs: rs4780836, rs2605140, rs11690265, rs692854, and rs13380649. Results highlight the significance of sampling uniformity followed by stratified (e.g., ancestry, gender, developmental period) analysis, and wider selection of features, to generate better prediction scores allowing a more accurate estimation of AUD development.
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Alcoholismo , Negro o Afroamericano/genética , Anciano , Alcoholismo/genética , Biomarcadores , Niño , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Aprendizaje Automático , Masculino , Estados UnidosRESUMEN
Genetic predispositions and environmental influences both play an important role in adolescent externalizing behavior; however, they are not always independent. To elucidate gene-environment interplay, we examined the interrelationships between externalizing polygenic risk scores, parental knowledge, and peer substance use in impacting adolescent externalizing behavior across two time-points in a high-risk longitudinal sample of 1,200 adolescents (764 European and 436 African ancestry; Mage = 12.99) from the Collaborative Study on the Genetics of Alcoholism. Results from multivariate path analysis indicated that externalizing polygenic scores were directly associated with adolescent externalizing behavior but also indirectly via peer substance use, in the European ancestry sample. No significant polygenic association nor indirect effects of genetic risk were observed in the African ancestry group, likely due to more limited power. Our findings underscore the importance of gene-environment interplay and suggest peer substance use may be a mechanism through which genetic risk influences adolescent externalizing behavior.
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Conducta del Adolescente , Trastornos Relacionados con Sustancias , Adolescente , Niño , Humanos , Estudios Longitudinales , Herencia Multifactorial/genética , Responsabilidad Parental , Padres , Grupo Paritario , Factores de Riesgo , Trastornos Relacionados con Sustancias/genéticaRESUMEN
An increased propensity for risk taking is a hallmark of adolescent behavior with significant health and social consequences. Here, we elucidated cortical and subcortical regions associated with risky and risk-averse decisions and outcome evaluation using the Balloon Analog Risk Task in a large sample of adolescents (n = 256, 56% female, age 14 ± 0.6), including the level of risk as a parametric modulator. We also identified sex differences in neural activity. Risky decisions engaged regions that are parts of the salience, dorsal attention, and frontoparietal networks, but only the insula was sensitive to increasing risks in parametric analyses. During risk-averse decisions, the same networks covaried with parametric levels of risk. The dorsal striatum was engaged by both risky and risk-averse decisions, but was not sensitive to escalating risk. Negative-outcome processing showed greater activations than positive-outcome processing. Insula, lateral orbitofrontal cortex, middle, rostral, and superior frontal areas, rostral and caudal anterior cingulate cortex were activated only by negative outcomes, with a subset of regions associated with negative outcomes showing greater activation in females. Taken together, these results suggest that safe decisions are predicted by more accurate neural representation of increasing risk levels, whereas reward-related processes play a relatively minor role.
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Conducta del Adolescente/fisiología , Encéfalo/fisiología , Toma de Decisiones/fisiología , Asunción de Riesgos , Caracteres Sexuales , Gemelos , Adolescente , Conducta del Adolescente/psicología , Encéfalo/diagnóstico por imagen , Niño , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/tendencias , Masculino , Desempeño Psicomotor/fisiología , Gemelos/psicologíaRESUMEN
Neural correlates of decision making under risk are being increasingly utilized as biomarkers of risk for substance abuse and other psychiatric disorders, treatment outcomes, and brain development. This research relies on the basic assumption that fMRI measures of decision making represent stable, trait-like individual differences. However, reliability needs to be established for each individual construct. Here we assessed long-term test-retest reliability (TRR) of regional brain activations related to decision making under risk using the Balloon Analogue Risk Taking task (BART) and identified regions with good TRRs and familial influences, an important prerequisite for the use of fMRI measures in genetic studies. A secondary goal was to examine the factors potentially affecting fMRI TRRs in one particular risk task, including the magnitude of neural activation, data analytical approaches, different methods of defining boundaries of a region, and participant motion. For the average BOLD response, reliabilities ranged across brain regions from poor to good (ICCs of 0 to 0.8, with a mean ICC of 0.17) and highest reliabilities were observed for parietal, occipital, and temporal regions. Among the regions that were of a priori theoretical importance due to their reported associations with decision making, the activation of left anterior insula and right caudate during the decision period showed the highest reliabilities (ICCs of 0.54 and 0.63, respectively). Among the regions with highest reliabilities, the right fusiform, right rostral anterior cingulate and left superior parietal regions also showed high familiality as indicated by intrapair monozygotic twin correlations (ranging from 0.66 to 0.69). Overall, regions identified by modeling the average BOLD response to a specific event type (rather than its modulation by a parametric regressor), regions including significantly activated vertices (compared to a whole parcel), and regions with greater magnitude of task-related activations showed greater reliabilities. Participant motion had a moderate negative effect on TRR. Regions activated during decision period rather than outcome period of risky decisions showed the greatest TRR and familiality. Regions with reliable activations can be utilized as neural markers of individual differences or endophenotypes in future clinical neuroscience and genetic studies of risk-taking.
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Encéfalo/fisiología , Toma de Decisiones/fisiología , Imagen por Resonancia Magnética/métodos , Asunción de Riesgos , Mapeo Encefálico/métodos , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Shared genetic factors contribute to the high degree of comorbidity among externalizing problems (e.g. substance use and antisocial behavior). We leverage this common genetic etiology to identify genetic influences externalizing problems in participants from the Collaborative Study on the Genetics of Alcoholism (European ancestry = 7568; African ancestry = 3274). We performed a family-based genome-wide association study (GWAS) on externalizing scores derived from criterion counts of five DSM disorders (alcohol dependence, alcohol abuse, illicit drug dependence, illicit drug abuse, and either antisocial personality disorder or conduct disorder). We meta analyzed these results with a similar measure of externalizing in an independent sample, Spit for Science (combined sample N = 15,112). We did not discover any robust genome-wide significant signals. Polygenic scores derived from the ancestry-specific GWAS summary statistics predicted externalizing problems in an independent European ancestry sample, but not in those of African ancestry. However, these PRS were no longer significant after adjusting for multiple testing. Larger samples with deep phenotyping are necessary for the discovery of SNPs related to externalizing problems.
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Trastorno de Personalidad Antisocial/genética , Trastornos Relacionados con Sustancias/genética , Adolescente , Adulto , Alcoholismo/genética , Niño , Comorbilidad , Trastorno de la Conducta/genética , Salud de la Familia , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
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. METHODS: Data from the Collaborative Study on the Genetics of Alcoholism (COGA) were utilized to compute the density and dichotomous measures. Only subjects and their family members with DSM-5 AUD diagnostic information obtained through direct interviews using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) were included in the study. Area under receiver operating characteristic curves were used to compare the diagnostic accuracy of FH measures at classifying DSM-5 AUD diagnosis. Logistic and linear regression models were used to examine associations of FH measures with alcohol outcomes. RESULTS: Density measures had greater diagnostic accuracy at classifying AUD diagnosis, whereas dichotomous measures presented diagnostic accuracy closer to random chance. Both dichotomous and density measures were significantly associated with likelihood of AUD, early onset of regular drinking, and low parietal P3 amplitude, but density measures presented consistently more robust associations. Further, variations in these associations were observed such that among males (vs. females) and Whites (vs. Blacks), associations of alcohol outcomes with density (vs. dichotomous) measures were greater in magnitude. CONCLUSIONS: Density (vs. dichotomous) measures seem to present more robust associations with alcohol outcomes. However, associations of dichotomous and density FH measures with different alcohol outcomes (behavioral vs. neural) varied across gender and race/ethnicity. These findings have great applicability for alcohol research examining FH of AUD.
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Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Factores Raciales/estadística & datos numéricos , Factores Sexuales , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/genética , Población Negra/estadística & datos numéricos , Humanos , Anamnesis , Fenotipo , Curva ROC , Factores de Riesgo , Sensibilidad y Especificidad , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Previous research has demonstrated significant relationships between obesity and brain structure. Both phenotypes are heritable, but it is not known whether they are influenced by common genetic factors. We investigated the genetic etiology of the relationship between individual variability in brain morphology and BMIz using structural MRI in adolescent twins. METHOD: The sample (nâ¯=â¯258) consisted of 54 monozygotic and 75 dizygotic twin pairs (mean(SD) ageâ¯=â¯13.61(0.505), BMIzâ¯=â¯0.608(1.013). Brain structure (volume and density of gray and white matter) was assessed using VBM. Significant voxelwise heritability of brain structure was established using the Accelerated Permutation inference for ACE models (APACE) program, with structural heritability varying from 15 to 97%, depending on region. Bivariate heritability analyses were carried out comparing additive genetic and unique environment models with and without shared genetics on BMIz and the voxels showing significant heritability in the APACE analyses. RESULTS: BMIz was positively related to gray matter volume in the brainstem and thalamus and negatively related to gray matter volume in the bilateral uncus and medial orbitofrontal cortex, gray matter density in the cerebellum, prefrontal lobe, temporal lobe, and limbic system, and white matter density in the brainstem. Bivariate heritability analyses showed that BMIz and brain structure share â¼1/3 of their genes and that â¼95% of the phenotypic correlation between BMIz and brain structure is due to shared additive genetic influences. These regions included areas related to decision-making, motivation, liking vs. wanting, taste, interoception, reward processing/learning, caloric evaluation, and inhibition. CONCLUSION: These results suggested genetic factors are responsible for the relationship between BMIz and heritable BMIz related brain structure in areas related to eating behavior.
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Índice de Masa Corporal , Tronco Encefálico/anatomía & histología , Cerebelo/anatomía & histología , Corteza Cerebral/anatomía & histología , Sustancia Gris/anatomía & histología , Sistema Límbico/anatomía & histología , Tálamo/anatomía & histología , Sustancia Blanca/anatomía & histología , Adolescente , Tronco Encefálico/diagnóstico por imagen , Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Niño , Femenino , Sustancia Gris/diagnóstico por imagen , Humanos , Sistema Límbico/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Fenotipo , Tálamo/diagnóstico por imagen , Gemelos Dicigóticos , Gemelos Monocigóticos , Sustancia Blanca/diagnóstico por imagenRESUMEN
The human brain shows remarkable development of functional brain activity from childhood to adolescence. Here, we investigated whether electroencephalogram (EEG) recordings are suitable for predicting the age of children and adolescents. Moreover, we investigated whether overestimation or underestimation of age was stable over longer time periods, as stable prediction error can be interpreted as reflecting individual brain maturational level. Finally, we established whether the age-prediction error was genetically determined. Then, 3 min eyes-closed resting-state EEG data from the longitudinal EEG studies of Netherlands Twin Register (NTR; n = 836) and Washington University in St. Louis (n = 702) were used at ages 5, 7, 12, 14, 16, and 18. Longitudinal data were available within childhood (5-7 years) and adolescence (16-18 years). We calculated power in 1 Hz wide bins (1-24 Hz). Random forest (RF) regression and relevance vector machine with sixfold cross-validation were applied. The best mean absolute prediction error was obtained with RF (1.22 years). Classification of childhood versus puberty/adolescence reached over 94% accuracy. Prediction errors were moderately to highly stable over periods of 1.5-2.1 years (0.53 < r < 0.74) and signifcantly affected by genetic factors (heritability between 42 and 79%). Our results show that age prediction from low-cost EEG recordings is comparable in accuracy to those obtained with magnetic resonance imaging. Children and adolescents showed stable overestimation or underestimation of their age, which means that some participants have stable brain activity patterns that reflect those of an older or younger age, and could therefore reflect individual brain maturational level. This prediction error is heritable, suggesting that genes underlie maturational level of functional brain activity. We propose that age prediction based on EEG recordings can be used for tracking neurodevelopment in typically developing children, in preterm children, and in children with neurodevelopmental disorders.
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Envejecimiento/fisiología , Encéfalo/fisiología , Electroencefalografía , Adolescente , Niño , Desarrollo Infantil/fisiología , Femenino , Humanos , Aprendizaje Automático , Masculino , Sistema de RegistrosRESUMEN
We studied the pattern of personality development in a longitudinal population-based sample of 752 American adolescents. Personality was assessed reliably with the Junior Temperament and Character Inventory at 12, 14, and 16 years of age. The rank-order stability of Junior Temperament and Character Inventory traits from age 12 to 16 was moderate (r = .35). Hierarchical linear modeling of between-group variance due to gender and within-group variance due to age indicated that harm avoidance and persistence decreased whereas self-directedness and cooperativeness increased from age 12 to 16. Novelty seeking, reward dependence, and self-transcendence increased from age 12 to 14 and then decreased. This biphasic pattern suggests that prior to age 14 teens became more emancipated from adult authorities while identifying more with the emergent norms of their peers, and after age 14 their created identity was internalized. Girls were more self-directed and cooperative than boys and maintained this advantage from age 12 to 16. Dependability of temperament at age 16 was mainly predicted by the same traits at earlier ages. In contrast, maturity of character at age 16 was predicted by both temperament and character at earlier ages. We conclude that character develops rapidly in adolescence to self-regulate temperament in accord with personally valued goals shaped by peers.
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Carácter , Desarrollo de la Personalidad , Temperamento , Adolescente , Niño , Femenino , Humanos , Masculino , Inventario de PersonalidadRESUMEN
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.
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Bacterias/clasificación , Bacterias/genética , Biodiversidad , Intestinos/microbiología , Metagenoma , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Preescolar , Heces/microbiología , Femenino , Geografía , Humanos , Lactante , Malaui , Masculino , Persona de Mediana Edad , Filogenia , ARN Ribosómico 16S/genética , Gemelos Dicigóticos , Gemelos Monocigóticos , Estados Unidos , Venezuela , Adulto JovenRESUMEN
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.
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Trastornos Relacionados con Alcohol/etiología , Conducta Impulsiva , Adolescente , Trastornos Relacionados con Alcohol/psicología , Femenino , Humanos , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
To investigate familial influences on the full range of variability in attention and activity across adolescence, we collected maternal ratings of 339 twin pairs at ages 12, 14, and 16, and estimated the transmitted and new familial influences on attention and activity as measured by the Strengths and Weaknesses of Attention-Deficit/Hyperactivity Disorder Symptoms and Normal Behavior Scale. Familial influences were substantial for both traits across adolescence: genetic influences accounted for 54%-73% (attention) and 31%-73% (activity) of the total variance, and shared environmental influences accounted for 0%-22% of the attention variance and 13%-57% of the activity variance. The longitudinal stability of individual differences in attention and activity was largely accounted for by familial influences transmitted from previous ages. Innovations over adolescence were also partially attributable to familial influences. Studying the full range of variability in attention and activity may facilitate our understanding of attention-deficit/hyperactivity disorder's etiology and intervention.
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Trastorno por Déficit de Atención con Hiperactividad/psicología , Atención/fisiología , Enfermedades en Gemelos/psicología , Familia/psicología , Medio Social , Gemelos/psicología , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/genética , Enfermedades en Gemelos/genética , Femenino , Humanos , Individualidad , Estudios Longitudinales , Masculino , Fenotipo , Gemelos/genéticaRESUMEN
Background: Previous studies have shown that brain volume is negatively associated with cigarette smoking, but there is an ongoing debate about whether smoking causes lowered brain volume or a lower brain volume is a risk factor for smoking. We address this debate through multiple methods that evaluate directionality: Bradford Hill's criteria, which are commonly used to understand a causal relationship in epidemiological studies, and mediation analysis. Methods: In 32,094 participants of European descent from the UK Biobank dataset, we examined the relationship between a history of daily smoking and brain volumes, as well as an association of genetic risk score to ever smoking with brain volume. Results: A history of daily smoking was strongly associated with decreased brain volume, and a history of heavier smoking was associated with a greater decrease in brain volume. The strongest association was between total gray matter volume and a history of daily smoking (effect size = -2964 mm3, p = 2.04 × 10-16), and there was a dose-response relationship with more pack years smoked associated with a greater decrease in brain volume. A polygenic risk score for smoking initiation was strongly associated with a history of daily smoking (effect size = 0.05, p = 4.20 × 10-84), but only modestly associated with total gray matter volume (effect size = -424 mm3, p = .01). Mediation analysis indicated that a history of daily smoking mediated the relationship between the smoking initiation polygenic risk score and total gray matter volume. Conclusions: A history of daily smoking is strongly associated with a decreased total brain volume.
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INTRODUCTION: The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and APOE genotype on total hippocampal volume. METHODS: Utilizing neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and APOE with hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling. RESULTS: Total hippocampal volume declined with age, with significant differences by APOE genotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at age 76. DISCUSSION: The association of APOE and hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance of APOE genotype in determining when to begin screening for AD.
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Background and Hypothesis: The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals. Study Design: We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa. Study Results: This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations. Conclusions: KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia.
RESUMEN
Introduction: Suicidal thoughts and behaviors have partially distinct genetic etiologies. Methods: We used PRS-CS to create polygenic risk scores (PRSs) from GWAS of non-suicidal self-injury, broad-sense self-harm ideation, nonfatal suicide attempt, death by suicide, and depression. Using mixed-effect models, we estimated whether these PRSs were associated with a range of suicidal thoughts and behaviors in the Collaborative Study on the Genetics of Alcoholism (N = 7,526). Results: All PRSs were significantly associated with suicidal ideation and suicide attempt (betas = 0.08-0.44, false discovery rate [FDR] <0.023). All PRSs except non-suicidal self-injury PRS were associated with active suicidal ideation (betas = 0.14-0.22, FDR <0.003). Several associations remained significant in models where all significant PRSs were included as simultaneous predictors, and when all PRSs predicted suicide attempt, the PRS together explained 6.2% of the variance in suicide attempt. Significant associations were also observed between some PRSs and persistent suicidal ideation, non-suicidal self-injury, compounded suicide attempt, and desire to die. Conclusion: Our findings suggest that PRS for depression does not explain the entirety of the variance in suicidal thoughts and behaviors, with PRS specifically for suicidal thoughts and behaviors making additional and sometimes unique contributions.