Background Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation. Methods We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups. Results Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells. Conclusions Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery.

Rumination is an established cognitive vulnerability for depression. Despite substantial work on the environmental origins of rumination, the heritability of rumination has not been examined and it is not known whether rumination accounts for some of the genetic vulnerability associated with depression. 756 adolescent twins ages 12–14 years completed the Response Styles Questionnaire and multiple measures of depressive symptoms. Brooding correlated positively and distraction correlated negatively with concurrent depressive symptoms. Estimated heritabilites were 54% for depression, 21% for brooding, 37% for reflection, and 30% for distraction. Bivariate genetic analyses suggested that (1) individual differences in distraction share both genetic and environmental sources of variation with depression; and (2) although the heritable influences on brooding are small, these heritable influences account for the majority of the relationship between brooding and depression (h2 = .62).

Although several studies have shown that pubertal tempo and timing are shaped by genetic and environmental factors, few studies consider to what extent endocrine triggers of puberty are shaped by genetic and environmental factors. Doing so moves the field from examining correlated developmentally-sensitive biomarkers toward understanding what drives those associations. Two puberty related hormones, dehydroepiandrosterone and testosterone, were assayed from salivary samples in 118 MZ (62 % female), 111 same sex DZ (46 % female) and 103 opposite-sex DZ twin pairs, aged 12–16 years (M = 13.1, SD = 1.3). Pubertal status was assessed with a composite of mother- and self-reports. We used biometric models to estimate the genetic and environmental influences on the variance and covariance in testosterone and DHEA, with and without controlling for their association with puberty, and to test for sex differences. In males, the variance in testosterone and pubertal status was due to shared and non-shared environmental factors; variation in DHEA was due to genetic and non-shared environmental factors. In females, variance in testosterone was due to genetic and non-shared environmental factors; genetic, shared, and non-shared environmental factors contributed equally to variation in DHEA. In males, the testosterone-DHEA covariance was primarily due to shared environmental factors that overlapped with puberty as well as shared and non-shared environmental covariation specific to testosterone and DHEA. In females, the testosterone-DHEA covariance was due to genetic factors overlapping with pubertal status, and shared and non-shared environmental covariation specific to testosterone and DHEA.

Although a robust literature has linked stable, high levels of fear across childhood to increased risk for anxiety problems, less is known about alternative pathways to anxiety. We tested two putatively normative developmental pathways of early fearfulness for their distinct associations with behavioral (anxiety related behaviors and symptoms) and biological (diurnal cortisol) markers of anxiety risk in middle childhood in a community-based sample (n=107). Steeper increases in fear from six to 36 months predicted more parent-reported anxiety symptoms at age eight years. Additionally, children who exhibited steep increases in fear during infancy were over-represented among children with diagnoses of separation anxiety disorder at age eight years. Finally, we showed that steeper increases in fearfulness in infancy predicted flatter slopes of diurnal cortisol at age eight years for girls. Thus, differences in stranger fear across infancy may indicate varying degrees of risk for anxious behaviors in later childhood.

The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene–environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.