Partitioning the Genomic Components of Behavioral Disinhibition and Substance Use (Disorder) Using Genomic Structural Equation Modeling.

Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SU), substance use disorder (SUD), and other (non-SU/SUD) "behavioral disinhibition" (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models-each describing SUB, SUD, or BD traits--based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then applied trivariate Cholesky decomposition to these factors in order to identify BD-specific genomic variation and assess the partitioning of BD's genetic covariance with each of the other facets. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large zero-order correlation (rg=.803). BD correlated strongly with the SUD (rg=.774) and SUB factors (rg=.778). In our initial decompositions, 33% of total BD variance remained after removing variance associated with SUD and SUB. The majority of covariance between BD and SU and between BD and SUD was shared across all factors. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their zero-order correlation increased to rg=.861; in corresponding decompositions, BD-specific variance decreased to 27%. In summary, BD, SU, and SUD were highly genetically correlated at the latent factor level, and a significant minority of genomic BD variation was not shared with SU and/or SUD. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates.

Reinvigoration of a Diversity, Equity, and Inclusion Committee at the Institute for Behavioral Genetics: Student-driven Progress.

Extremist far-right ideologies, including scientifically inaccurate beliefs about race, are on the rise (Mierina and Koroleva 2015; Youngblood 2020); individuals perpetuating such ideologies occasionally cite genetics research, including behavioral genetics research. This highlights the need for behavioral geneticists to actively confront extremist ideology and promote anti-racism. We emphasize the need for Diversity, Equity and Inclusion (DEI) committees within behavioral genetics institutions. DEI committees can lead to: greater awareness of ways in which behavioral genetics has been misused (historically and currently) to harm minoritized communities, increased discussions on conducting ethical behavioral genetics research, and increased collaboration for conducting more diverse behavioral genetics research. We discuss the activities and goals of the student-driven DEI committee at the Institute for Behavior Genetics (IBG). At the same time, we acknowledge we have a long way to go, both as a committee and as a field. Our committee is still in its early stages; we discuss challenges to increasing DEI in the field and present future goals for both IBG and the behavioral genetics community as we explore the process of implementing DEI work.

South Asia: The Missing Diverse in Diversity.

South Asia, making up around 25% of the world's population, encompasses a wide range of individuals with tremendous genetic and environmental diversity. This region, which spans eight countries, is home to over 4500 anthropologically defined groups that speak numerous languages and have an array of religious beliefs and cultures, making it one of the most diverse places in the world. Much of the region's rich genetic diversity and structure is the result of a complex combination of population history, migration patterns, and endogamous practices. Despite the overwhelming size and diversity, South Asians have often been underrepresented in genetic research, making up less than 2% of the participants in genetic studies. This has led to a lack of population specific understanding of genetic disease risks. We aim to raise awareness about underlying genetic diversity in this ancestry group, call attention to the lack of representation of the group, and to highlight strategies for future studies in South Asians.

Subjective effects as predictors of substance use disorders in a clinical sample: A longitudinal study.

BACKGROUND: The literature on the association between subjective effects (SEs; i.e., how an individual perceives their physiological and psychological reactions to a drug) and substance use disorders (SUDs) is largely limited to community samples. The present study addressed the following aims in a clinical sample: whether SEs predict general versus substance-specific SUD in adolescence and adulthood after controlling for conduct disorder symptoms (CDsymp); whether SEs predict SUDs across drug classes; whether SEs predict change in SUD from adolescence to adulthood; and whether there are racial/ethnic differences in associations. METHODS: Longitudinal analyses were conducted using data from a sample of 744 clinical probands recruited from residential and outpatient SUD treatment facilities in CO during adolescence (Mage = 16.26) and re-assessed twice in adulthood (Mages = 22.56 and 28.96), approximately seven and twelve years after first assessment. SEs and CDsymp were assessed in adolescence. SUD severity was assessed at adolescence and twice during adulthood. RESULTS: SEs assessed in adolescence robustly predicted general SUD for legal and illegal substances in adolescence and adulthood, whereas CDsymp predicted SUD primarily in adolescence. Higher positive and negative SEs in adolescence were associated with greater SUD severity after controlling for CDsymp, with similar magnitudes. Results indicated cross-substance effects of SEs on SUD. We found no evidence for racial/ethnic differences in associations. CONCLUSIONS: We investigated the progression of SUD in a high-risk sample with greater odds of sustained SUD. In contrast to CDsymp, both positive and negative SEs consistently predicted general SUD across substances in adolescence and adulthood.

Exploring Relationships Between Internalizing Problems and Risky Sexual Behavior: A Twin Study.

Previous research links risky sexual behavior (RSB) to externalizing problems and to substance use, but little research has been conducted on relationships between internalizing problems (INT) and RSB. The current study addresses that literature gap, using both a twin sample from Colorado (N = 2567) and a second twin sample from Minnesota (N = 1131) in attempt to replicate initial results. We explored the hypothesis that the latent variable INT would be more strongly associated with the latent variable RSB for females than for males, examining relationships between INT and RSB via phenotypic confirmatory factor analysis and multivariate twin analyses. We found a small but significant phenotypic association between the latent variables. However, despite using two large twin samples, limited power restricted our ability to identify the genetic and environmental mechanisms underlying this association. Our sex differences hypothesis was not fully supported in either sample and requires further investigation. Our findings illustrate the complexity of the relationship between internalizing problems and risky sexual behavior.

The effects of cannabis use on physical health: A co-twin control study.

BACKGROUND: Research on the influence of cannabis use on anthropometrics, cardiovascular and pulmonary function, and other indicators of physical health has reported mixed results. We examined whether cannabis frequency is associated with physical health outcomes phenotypically and after controlling for shared genetic and environmental factors via a longitudinal co-twin control design. METHODS: We tested the phenotypic associations of adolescent, young adult, and adult cannabis frequency with adult physical health. Next, we ran multilevel models to test if significant phenotypic associations remained at the between-family and within-twin pair levels. Participants include 677 individual twins (308 twin pairs) aged 25-35. RESULTS: At the phenotypic level, adolescent cannabis use was associated with less adult exercise engagement (b = - 0.846 min, p = .000). Adult cannabis use was associated with a lower resting heart rate (HR; b = - 0.170 bpm, p = .001) and more frequent appetite loss (b = 0.018, p = .000). Only between-family effects were significant for adolescent cannabis use and exercise engagement (b = - 1.147 min, p = .000) and adult cannabis use and appetite loss frequency (b = 0.041, p = .002). The total within-twin (b = - 0.184, p = .014), MZ only (b = - 0.304, p = .003), and between-family effects (b = - 0.164, p = .025) were significant between adult cannabis use and a lower resting HR, which persisted after controlling for familial confounds and other substance use. CONCLUSIONS: The associations between cannabis use with exercise engagement and frequency of appetite loss are explained by familial confounding while the association between cannabis use and resting HR was not. These results do not support a causal association between cannabis use once a week and poorer physical health effects among adults aged 25-35.

Executive functions as a mediator of childhood maltreatment on adult psychopathology: A longitudinal mediation analysis comparing maltreatment factor models.

BACKGROUND: Childhood maltreatment (CM), executive functions (EFs), and psychiatric disorders all correlate highly. Changes in EFs during adolescence related to CM present a possible mediating mechanism for the development of psychiatric disorders, yet no study has analyzed this longitudinally while comparing predictive capacity of different CM factor structures. We hypothesized that changes in EFs from adolescence to adulthood would mediate, in part, associations between CM, internalizing disorders (INT), and anti-social personality disorder (ASPD) while different subtypes of CM would differentially predict INT and ASPD. OBJECTIVE: This study longitudinally examined the mediating effects of EFs on associations between CM, INT, and ASPD while comparing prediction of two CM factor structures. PARTICIPANTS: High-risk subjects selected for drug use in adolescence (N = 658) from mean ages 16 to 23. METHODS: A Bayesian structural equation model was deployed to analyze change in EFs as a mediator of the relationship between CM and adult INT and ASPD. CM was measured using two factor structures: a single overall factor and four correlated factors representing CM subtypes. RESULTS: CM significantly predicted INT and ASPD but there was no evidence that the relationship was substantially mediated through EFs. High correlations among subtypes of CM limited the unique predictions of each subtype on INT and ASPD. CONCLUSION: In this high-risk sample, the collinearity of CM subtypes obscured their predictions of outcome measures supporting the use of one CM factor. EFs did not significantly mediate associations between CM and psychiatric disorders, but further research on these relationships is warranted.

Musical instrument engagement in adolescence predicts verbal ability 4 years later: A twin and adoption study.

Individual differences in music traits are heritable and correlated with the development of cognitive and communication skills, but little is known about whether diverse modes of music engagement (e.g., playing instruments vs. singing) reflect similar underlying genetic/environmental influences. Moreover, the biological etiology underlying the relationship between musicality and childhood language development is poorly understood. Here we explored genetic and environmental associations between music engagement and verbal ability in the Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife). Adolescents (N = 1,684) completed measures of music engagement and intelligence at approximately age 12 and/or multiple tests of verbal ability at age 16. Structural equation models revealed that instrument engagement was highly heritable (a² = .78), with moderate heritability of singing (a² = .43) and dance engagement (a² = .66). Adolescent self-reported instrument engagement (but not singing or dance engagement) was genetically correlated with age 12 verbal intelligence and still was associated with age 16 verbal ability, even when controlling for age 12 full-scale intelligence, providing evidence for a longitudinal relationship between music engagement and language beyond shared general cognitive processes. Together, these novel findings suggest that shared genetic influences in part accounts for phenotypic associations between music engagement and language, but there may also be some (weak) direct benefits of music engagement on later language abilities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

An examination of genetic and environmental factors related to negative personality traits, educational attainment, and economic success.

Personality variables are associated with educational attainment and socioeconomic outcomes. In this study we incorporated a polygenic score derived from the largest genome-wide association study (GWAS) of educational attainment to date (Lee et al., 2018) into the Interactionist Model of R. D. Conger, Martin, and Masarik (2021) that describes the influence of socioeconomic factors on individual development. The inclusion of a polygenic score predictive of educational attainment (PS-Edu) into this model, and the use of the multigeneration, longitudinal Family Transitions Project (FTP) provide a unique opportunity to investigate genetic and environmental influences on the development of negative personality traits and educational and economic outcomes. The FTP is a three-generation sample. This study utilized data from the first generation (G1; mean age 40 at initiation of the FTP) and second generation (G2; assessed at mean ages 18 and 30). Participants are approximately 50% female, 99% of European ancestry, primarily from lower to middle class SES. PS-Edu was significantly correlated with educational attainment in both generations of the FTP, accounting for 4.1 to 6.7% of the variance. Findings confirm that PS-Edu is a complex genetic index that is correlated with all of the socioeconomic constructs in the model. Results suggest potential gene-environment correlation or common genetic influences underlie associations among parenting investments, negative personality traits, and educational attainment. Genetic variance captured by PS-Edu was mediated substantially through G1 parental investments. Although study limitations warrant cautious interpretation, we demonstrate the promise of including polygenic scores in developmental models to better understand genetic and environmental influences on human development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Familial factors may not explain the effect of moderate-to-heavy cannabis use on cognitive functioning in adolescents: a sibling-comparison study.

AIMS: To examine whether moderate adolescent cannabis use has neurocognitive effects that are unexplained by familial confounds, which prior family-controlled studies may not have identified. DESIGN: A quasi-experimental, sibling-comparison design was applied to a prospective, observational study of adolescents with moderate cannabis use. Participants were recruited from 2001 to 2006 (mean age = 17 years). A second wave of data was collected from 2008 to 2013 (mean age = 24 years). SETTING: Two US metropolitan communities. PARTICIPANTS: A total of 1192 adolescents from 596 families participated in this study. Participants were primarily male (64%) and racially and ethnically diverse (non-Hispanic white = 45%). A sibling in each family was a clinical proband identified due to delinquent behaviors. Whereas prior family-controlled studies have used samples of primarily infrequent cannabis users (mean = 1-2 days/month), participants here endorsed levels of cannabis use comparable to findings from epidemiological cohort studies (mean = 7-9 days/month). MEASUREMENTS: Semi-structured clinical interviews assessed drug use, and a neuropsychological battery assessed cognitive abilities. Covariates included age at assessment, gender and alcohol use. FINDINGS: After correcting for multiple testing, a greater frequency and earlier onset of regular cannabis use were associated with poorer cognitive performance, specifically on tests of verbal memory. Further, after accounting for familial factors shared by siblings and alcohol use, poorer verbal memory performance was still associated with greater life-time frequency of cannabis use at wave 1 [b = -0.007 (-0.002, -0.012), adjusted P = 0.036]; earlier cannabis use at wave 2 [b = -0.12 (-0.05, -0.19), adjusted P = 0.006; b = -0.14 (-0.06, -0.23), adjusted P = 0.006]; and greater frequency of past 6 months use at wave 2 [b = -0.02 (-0.01, -0.03), adjusted P = 0.002; b = -0.02 (-0.01, -0.03), adjusted P = 0.008]. CONCLUSIONS: Moderate adolescent cannabis use may have adverse effects on cognitive functioning, specifically verbal memory, that cannot be explained by familial factors.

Etiological Overlap Between Sex Under the Influence and Number of Lifetime Sexual Partners.

Drug and alcohol use is associated with risky sexual behavior (RSB). It is unclear whether this association is due to correlated liabilities (e.g., third variables influencing both traits), or whether use of drugs and alcohol during sexual decision making increases RSB. This study addresses this question by fitting a series of biometrical models using over 800 twin pairs assessed in early adulthood (m = 25.21 years). Measures included an index of sex under the influence (e.g., frequency that drugs or alcohol affect sexual decision making), number of lifetime sexual partners, and a general measure of substance use. Analyses suggest the covariance among these measures is explained by both genetic and environmental correlated liabilities. The overlap was not specific to sex under the influence, but was shared with a measure of general substance use. Models testing necessary but not sufficient parameters for direction of causation suggest that sex under the influence is unlikely to cause an increase in RSB; more evidence for reverse causation was found.

The structure and subtypes of gambling activities: Genetic, psychiatric and behavioral etiologies of gambling frequency.

The multitude of gambling activities has given rise to heterogeneous ways of analyzing these behaviors and may partially underlie the lack of replication in gambling research. The current study used complementary analyses to investigate the structure, typology and etiology of gambling behaviors in a discovery sample of 2,116 twins (54.86% female; Mage = 24.90) and a replication sample of 619 siblings (30.37% female; Mage = 28.00). Our approach was twofold. First, we used confirmatory factor analyses to investigate the structure across the frequency of eight gambling activities. Second, we used factor mixture models to identify gambling frequency subtypes. We assessed associations with gambling frequency as well as conducted genetically informed analyses to estimate the role of genetic and environmental influences. Across samples, a two-factor model fit the data best, with a Common Gambling factor influencing all activities and a separate factor for Skill Gambling. Our study identified four gambling frequency subtypes, which resembled the typology from the Pathways Model. We found distinct demographic, psychiatric, behavioral and genetic risk profiles for the different gambling factors and subtypes with robust associations observed for male sex, risk-taking, sensation seeking, alcohol dependence and problem gambling. Controlling for shared genetic and environmental influences (via co-twin control modeling), we found that sensation seeking directly increased Common Gambling frequency. In sum, we illustrated the utility of multi-dimensional statistical techniques for disentangling the structure and typology from complex multivariate gambling data.

Genetic Architecture and Molecular Neuropathology of Human Cocaine Addiction.

We integrated genomic and bioinformatic analyses, using data from the largest genome-wide association study of cocaine dependence (CD; n = 6546; 82.37% with CD; 57.39% male) and the largest postmortem gene-expression sample of individuals with cocaine use disorder (CUD; n = 36; 51.35% with CUD; 100% male). Our genome-wide analyses identified one novel gene (NDUFB9) associated with the genetic predisposition to CD in African-Americans. The genetic architecture of CD was similar across ancestries. Individual genes associated with CD demonstrated modest overlap across European-Americans and African-Americans, but the genetic liability for CD converged on many similar tissue types (brain, heart, blood, liver) across ancestries. In a separate sample, we investigated the neuronal gene expression associated with CUD by using RNA sequencing of dorsal-lateral prefrontal cortex neurons. We identified 133 genes differentially expressed between CUD case patients and cocaine-free control subjects, including previously implicated candidates for cocaine use/addiction (FOSB, ARC, KCNJ9/GIRK3, NR4A2, JUNB, and MECP2). Differential expression analyses significantly correlated across European-Americans and African-Americans. While genes significantly associated with CD via genome-wide methods were not differentially expressed, two of these genes (NDUFB9 and C1qL2) were part of a robust gene coexpression network associated with CUD involved in neurotransmission (GABA, acetylcholine, serotonin, and dopamine) and drug addiction. We then used a "guilt-by-association" approach to unravel the biological relevance of NDUFB9 and C1qL2 in the context of CD. In sum, our study furthers the understanding of the genetic architecture and molecular neuropathology of human cocaine addiction and provides a framework for translating biological meaning into otherwise obscure genome-wide associations.SIGNIFICANCE STATEMENT Our study further clarifies the genetic and neurobiological contributions to cocaine addiction, provides a rapid approach for generating testable hypotheses for specific candidates identified by genome-wide research, and investigates the cross-ancestral biological contributions to cocaine use disorder/dependence for individuals of European-American and African-American ancestries.

Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.

To provide insights into the biology of opioid dependence (OD) and opioid use (i.e., exposure, OE), we completed a genome-wide analysis comparing 4503 OD cases, 4173 opioid-exposed controls, and 32,500 opioid-unexposed controls, including participants of European and African descent (EUR and AFR, respectively). Among the variants identified, rs9291211 was associated with OE (exposed vs. unexposed controls; EUR z = -5.39, p = 7.2 × 10-8). This variant regulates the transcriptomic profiles of SLC30A9 and BEND4 in multiple brain tissues and was previously associated with depression, alcohol consumption, and neuroticism. A phenome-wide scan of rs9291211 in the UK Biobank (N > 360,000) found association of this variant with propensity to use dietary supplements (p = 1.68 × 10-8). With respect to the same OE phenotype in the gene-based analysis, we identified SDCCAG8 (EUR + AFR z = 4.69, p = 10-6), which was previously associated with educational attainment, risk-taking behaviors, and schizophrenia. In addition, rs201123820 showed a genome-wide significant difference between OD cases and unexposed controls (AFR z = 5.55, p = 2.9 × 10-8) and a significant association with musculoskeletal disorders in the UK Biobank (p = 4.88 × 10-7). A polygenic risk score (PRS) based on a GWAS of risk-tolerance (n = 466,571) was positively associated with OD (OD vs. unexposed controls, p = 8.1 × 10-5; OD cases vs. exposed controls, p = 0.054) and OE (exposed vs. unexposed controls, p = 3.6 × 10-5). A PRS based on a GWAS of neuroticism (n = 390,278) was positively associated with OD (OD vs. unexposed controls, p = 3.2 × 10-5; OD vs. exposed controls, p = 0.002) but not with OE (p = 0.67). Our analyses highlight the difference between dependence and exposure and the importance of considering the definition of controls in studies of addiction.

Cocaine'omics: Genome-wide and transcriptome-wide analyses provide biological insight into cocaine use and dependence.

We investigated the genetic and molecular architecture of cocaine dependence (CD) and cocaine use by integrating genome-/transcriptome-wide analyses. To prioritize candidates for follow-up investigation, we also sought to translate gene expression findings across species. Using data from the largest genome-wide association study (GWAS) of CD to date (n = 3176, 74% with CD), we assessed genomic heritability, gene-based associations, and tissue enrichment. We detected a significant single-nucleotide polymorphism heritability of 28% for CD and identified three genes (two loci) underlying this predisposition: the C1qL2 (complement component C1 q like 2), KCTD20 (potassium channel tetramerization domain containing 20), and STK38 (serine/threonine kinase 38) genes. Tissue enrichment analyses indicated robust enrichment in numerous brain regions, including the hippocampus. We used postmortem human hippocampal RNA-sequencing data from previous study (n = 15, seven chronic cocaine users) to follow up genome-wide results and to identify differentially expressed genes/transcripts and gene networks underlying cocaine use. Cross-species analyses utilized hippocampal gene expression from a mouse model of cocaine use. Differentially expressed genes/transcripts in humans were enriched for the genes nominally associated with CD via GWAS (P < 0.05) and for differentially expressed genes in the hippocampus of cocaine-exposed mice. We identified KCTD20 as a central component of a hippocampal gene network strongly associated with human cocaine use, and this gene network was conserved in the mouse hippocampus. We outline a framework to map and translate genome-wide findings onto tissue-specific gene expression, which provided biological insight into cocaine use/dependence.

Onset of regular cannabis use and adult sleep duration: Genetic variation and the implications of a predictive relationship.

BACKGROUND: Limited evidence suggests that early cannabis use is associated with sleep problems. Research is needed to understand the developmental impact of early regular cannabis use on later adult sleep duration. METHODS: In a sample of 1656 adult twins (56% female, Mean age = 25.79yrs), linear mixed effects models were used to analyze the influence of retrospectively assessed age of onset of regular cannabis use on adult sleep duration controlling for sex, depression, and current substance use. Twin analyses provided genetic and environmental variance estimates as well as insights into the association and potential casual relationships between these traits. RESULTS: Earlier age of onset for regular cannabis use was significantly associated with shorter adult sleep duration on both weekdays (ß = -0.13, 95% CI = [-0.23, -0.04]) and weekends (ß = -0.18, 95% CI = [-0.27, -0.08]). Additive genetics significantly contributed to the onset of regular cannabis use (a2 = 76%, 95% CI = [68, 85]) and adult weekend sleep duration (a2 = 20%, 95% CI = [11, 32]). We found evidence of a significant genetic correlation (rA = -0.31, 95% CI = [-0.41, -0.15]) between these two traits and our best fitting model was consistent with early onset of regular cannabis use causing shorter adult weekend sleep duration (ß = -0.11, 95% CI = [-0.18, -0.03]). CONCLUSIONS: Our results are consistent with the hypothesis that early onset of regular cannabis use may have a negative impact on adult sleep duration.

Age of initiation and transition times to tobacco dependence: Early onset and rapid escalated use increase risk for dependence severity.

BACKGROUND: Research indicates that early tobacco initiation increases risk for dependence, but despite this, early initiation is associated with slower transitions to escalated tobacco use. In contrast to these findings, other studies suggest that rapid escalated tobacco use is associated with increased dependence outcomes. METHODS: Our sample was comprised of 5668 twins (2834 twin-pairs, mean age: 26.89, s.d = 4.42, 53.67% female, 57.69% monozygotic) from Colorado and Minnesota twin cohorts. We assessed the associations between 1) age of tobacco initiation and the speed of transitions (latency) to tobacco problem use and dependence and the associations between 2) age of initiation and latencies to tobacco problem use and dependence with tobacco dependence symptom severity. To further understand the etiological unfolding of these processes, we conducted univariate twin models and causally informative co-twin control models. RESULTS: After adjustment for covariates, we found that early tobacco initiation was associated with a slower transition from initiation to problem use but a faster transition from problem use to dependence. Additionally, we found that earlier initiation and faster transitions to tobacco problem use and dependence predicted greater tobacco dependence severity within twin pairs (consistent with causal influences). The contribution of shared genetic and environmental factors was also evident for these relationships. CONCLUSIONS: Our study further disentangles the role of early initiation with transition times to tobacco problem use and dependence. In addition to common risk factors, we found potential causal roles for early tobacco initiation and rapid escalated tobacco use with increased risk for tobacco dependence severity.

Temperament, childhood illness burden, and illness behavior in early adulthood.

OBJECTIVE: Illness behaviors-or responses to bodily symptoms-predict individuals' recovery and functioning; however, there has been little research on the early life personality antecedents of illness behavior. This study's primary aims were to evaluate (a) childhood temperament traits (i.e., emotionality and sociability) as predictors of adult illness behaviors, independent of objective health; and (b) adult temperament traits for mediation of childhood temperament's associations. METHOD: Participants included 714 (53% male; 350 adoptive family and 364 control family) children and siblings from the Colorado Adoption Project (CAP; Plomin & DeFries, 1983). Structural regression analyses evaluated paths from childhood temperament to illness behavior (i.e., somatic complaints, sick days, and medication use) at two adulthood assessments (CAP years 21 and 30). Analyses controlled for participant age, sex, family type (adoptive or control), adopted status, parent education/occupation, and middle childhood illnesses, doctor visits, and life events stress. RESULTS: Latent illness behavior factors were established across 2 adulthood assessments. Multilevel path analyses revealed that higher emotionality (fearfulness) in adulthood-but not childhood temperament-predicted higher levels of illness behavior at both assessments. Lastly, lower emotionality-fearfulness partially mediated the effect of higher childhood sociability on adult illness behavior. CONCLUSIONS: Results suggest the importance of childhood illness experiences and adult emotionality (fearfulness) in shaping illness behavior in early adulthood. They also suggest a small, protective role of childhood sociability on reduced trait fearfulness in adulthood. These findings broaden our understanding of the prospective links between temperament and illness behavior development, suggesting distinct associations from early life illness experiences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

APOE effects on cognition from childhood to adolescence.

The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = -0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment.

Childhood language development and later alcohol use behaviors.

BACKGROUND: Studies have shown a correlation between language abilities and alcohol use; however, results are inconsistent. A recent study using a discordant twin design showed an association between early child language development and later alcohol use behaviors; i.e., the twin with more advanced language abilities was more likely to try alcohol earlier in adolescence (Latvala et al., 2014). The authors suggested that this could result from better socialization of individuals with greater language abilities, which could lead to more opportunities for alcohol experimentation. The findings by Latvala et al. raise interesting questions, but the study has limitations, and replication is needed. METHOD: We aimed to replicate and build upon these results utilizing 488 same sex twin pairs from the Colorado Longitudinal Twin Study, a longitudinal sample with quantitative measures of language abilities starting when the twins were 14 months old. RESULTS: We found no significant correlations between a latent measure of child language abilities or measures of general cognitive ability at ages 14, 20, and 24 months and a latent alcohol use variable at ages 17 and 22 years. CONCLUSION: Our results did not replicate the association between early language ability and later alcohol use reported by Latvala et al. Possible reasons for differing results across samples, including varying cultural norms as well as differences in educational attainment, peer influences, and novelty seeking, were discussed.