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Dysregulation of biological stress response, as measured by cortisol output, has been a primary candidate mechanism for how social experiences become biologically embedded. Cortisol is the primary output of the hypothalamic pituitary adrenal (HPA) axis. Cortisol levels vary systematically across the day and change in response to both sudden, acute stress experiences as well as prolonged exposure to environmental stress. Using data from 8- to 15-year-old twins in the Texas Twin Project, we investigate the extent to which genetic influences are shared across different measures of cortisol output: chronic cortisol accumulations in hair (n = 1,104), diurnal variation in salivary output (n = 488), and salivary response to a standardized, acute in-laboratory stressor (n = 537). Multivariate twin models indicate that genetic factors regulating cortisol response to the in-laboratory stressor are separable from those regulating baseline cortisol levels, naturally occurring diurnal variation in cortisol, and hair cortisol levels. These findings illustrate that novel environments can reveal unique genetic variation, reordering people in terms of their observed phenotype rather than only magnifying or mitigating preexisting differences.

Attention-Deficit Hyperactivity Disorder (ADHD) is a heterogeneous disorder that is highly impairing. Early, accurate diagnosis maximizes long-term positive outcomes for youth with ADHD. Tests of executive functioning (EF) are potential tools for screening and differential diagnosis of ADHD subtypes. However, previous research has been inconsistent regarding the specificity and magnitude of EF deficits across ADHD subtypes. Here, we advance knowledge of the EF-ADHD relationship by using: (1) dimensional latent factor models of ADHD that captures the heterogeneity of expression, and (2) a comprehensive, reliable battery of EF tasks and modeling relationships with a general factor of EF ability. We tested 1548 children and adolescents (ages 7-15 years) from the Texas Twin Project, a population-based cohort with a diverse socioeconomic and ethnic composition. We show that EF deficits were specific to the inattention domain of ADHD. Moreover, we found that the association between EF task performance and inattention was stable across sociodemographic groups. Our results demonstrate that failures of executive control are selectively manifested as covert inattentive symptoms, such as trouble with organization, forgetfulness, and distractedness, rather than overt symptoms, such as inappropriate talkativeness and interruption. Future research, utilizing a bifactor characterization of ADHD in clinical samples, is needed to further refine understanding of the nature of cognitive deficits in ADHD across the full range of symptom variation.

BackgroundWilliams syndrome (WS), a genetic disorder resulting from hemizygous microdeletion of chromosome 7q11.23, has emerged as a model for identifying the genetic architecture of socioemotional behavior. Common polymorphisms in GTF2I, which is found within the WS microdeletion, have been associated with reduced social anxiety in the general population. Identifying neural phenotypes affected by these polymorphisms would help advance our understanding not only of this specific genetic association but also of the broader neurogenetic mechanisms of variability in socioemotional behavior.MethodsThrough an ongoing parent protocol, the Duke Neurogenetics Study, we measured threat-related amygdala reactivity to fearful and angry facial expressions using functional magnetic resonance imaging, assessed trait personality using the Revised NEO Personality Inventory, and imputed GTF2I rs13227433 from saliva-derived DNA using custom Illumina arrays. Participants included 808 non-Hispanic Caucasian, African American, and Asian university students.ResultsThe GTF2I rs13227433 AA genotype, previously associated with lower social anxiety, predicted decreased threat-related amygdala reactivity. An indirect effect of GTF2I genotype on the warmth facet of extraversion was mediated by decreased threat-related amygdala reactivity in women but not men.ConclusionsA common polymorphism in the WS gene GTF2I associated with reduced social anxiety predicts decreased threat-related amygdala reactivity, which mediates an association between genotype and increased warmth in women. These results are consistent with reduced threat-related amygdala reactivity in WS and suggest that common variation in GTF2I contributes to broader variability in socioemotional brain function and behavior, with implications for understanding the neurogenetic bases of WS as well as social anxiety.

Children's cognitive functioning and educational performance are socially stratified. Social inequality, including classism and racism, may operate partly via epigenetic mechanisms that modulate neurocognitive development. Following preregistered analyses of data from 1,183 participants, ages 8 to 19 years, from the Texas Twin Project, we found that children growing up in more socioeconomically disadvantaged families and neighborhoods and children from marginalized racial/ethnic groups exhibit DNA methylation profiles that, in previous studies of adults, were indicative of higher chronic inflammation, lower cognitive functioning, and a faster pace of biological aging. Furthermore, children's salivary DNA methylation profiles were associated with their performance on in-laboratory tests of cognitive and academic skills, including processing speed, general executive function, perceptual reasoning, verbal comprehension, reading, and math. Given that the DNA methylation measures that we examined were originally developed in adults, our results suggest that children show molecular signatures that reflect the early life social determinants of lifelong disparities in health and cognition. [ABSTRACT FROM AUTHOR]