Background: Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research – cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifically meaningful variability between biological replicates, the application of the rICC has the potential to influence research strategies and tactics such that resources (e.g., finances, effort, number/volume of biospecimens) are allocated more efficiently and effectively.
Loneliness and cortisol are associated with social network regulation
Background: This study examines how loneliness and the body’s stress response system interact to regulate social connections. We suggest that the drive to reconnect signaled by loneliness can be accompanied physiologically by the production of cortisol, which can offer supportive coping resources. Thus, we investigated how loneliness, cortisol levels, and their interaction predicted changes in network connections in a social organization. Participants (n = 193; 53% female) provided friendship network data at two times. At time 1, participants reported on loneliness and donated saliva (later assayed for cortisol). Results revealed that concurrently, lonely individuals reported fewer friendships, whereas over time, they named more friends. These results support the hypothesis that loneliness is a signal to develop connections. We also explored whom lonely individuals befriended over time. Results showed that cortisol significantly moderated the preference for friends with a similar level of loneliness. Specifically, lonely individuals with higher cortisol befriended those who were less lonely over those who were lonelier. Thus, cortisol levels may serve an adaptive function in mobilizing resources to develop connections that fulfill social belongingness needs. Results supported the theorized signaling function of loneliness and revealed that loneliness and the stress response system interact to shape social connections.
An exploratory analysis of the joint contribution of HPA axis activation and motivation to early adolescent depressive symptoms.
Background:
This study examines the interactive contribution of the hypothalamic-pituitary-adrenal (HPA) axis and approach-avoidance motivation systems to longitudinal changes in depressive symptoms across the adolescent transition. In the summer prior to, or fall of, 4th grade, 132 youth (68 girls; 64 boys; M age = 9.46 years) participated in a social challenge task and reported on their depressive symptoms. In the winter of 6th grade, youth completed a semi-structured interview of depression and a self-report measure of approach-avoidance motivations. Analyses revealed two profiles of risk for adolescent depressive symptoms, with some gender differences: (1) excessive disengagement, reflected in HPA underactivation along with low approach motivation or high avoidance motivation; and (2) excessive engagement, reflected in HPA overactivation along with high approach motivation. This research highlights the importance of a multi-system perspective on development, suggesting that the implications of HPA dysregulation for depressive symptoms are contingent on adolescents’ tendencies toward approach versus avoidance.
Peer Networks, Psychobiology of Stress Response, and Adolescent Development
From the Oxford Handbook of Evolution, Biology, and Society:
A consistent focus of research has been on understanding how social relationships shape the activity of the biological stress response system. Progress has been made in characterizing these dynamics at the level of the individual, but significantly less is known about the role of social networks as a proximal ecology in which the stress response system is activated and contributes to human development. The focus of this chapter is on adolescence—a developmental period in which social relationships with peers represent both sources of social stress and opportunities for social buffering. It is proposed that considering peer social networks in which adolescents are embedded will augment understanding of the social context of psychosocial processes, including social status, rejection, isolation, bullying and victimization, and support, that are related to psychobiology of stress.
Anticipatory stress associated with functional magnetic resonance imaging: Implications for psychosocial stress research.
Background:
Stress tasks performed during functional magnetic resonance imaging (fMRI) elicit a relatively small cortisol response compared to stress tasks completed in a traditional behavioral laboratory, which may be due to apprehension of fMRI that elicits an anticipatory stress response. The present study investigated whether anticipatory stress is greater prior to research completed in an MRI environment than in a traditional behavioral laboratory. Anticipatory stress (indexed by cortisol) was greater prior to testing in the MRI environment than traditional behavioral laboratory. Furthermore, anticipation of fMRI elicited a cortisol response commensurate with the response to the stress task in the behavioral laboratory. However, in the MRI environment, post-stress cortisol was significantly lower than baseline cortisol. Taken together, these findings suggest the stress elicited by anticipation of fMRI may lead to acute elevations in cortisol prior to scanning, which may in turn disrupt the cortisol response to stress tasks performed during scanning.
An exploratory analysis of the joint contribution of HPA axis activation and motivation to early adolescent depressive symptoms.
Background:
This study examines the interactive contribution of the hypothalamic-pituitary-adrenal (HPA) axis and approach-avoidance motivation systems to longitudinal changes in depressive symptoms across the adolescent transition. In the summer prior to, or fall of, 4th grade, 132 youth (68 girls; 64 boys; M age = 9.46 years) participated in a social challenge task and reported on their depressive symptoms. In the winter of 6th grade, youth completed a semi-structured interview of depression and a self-report measure of approach-avoidance motivations. Analyses revealed two profiles of risk for adolescent depressive symptoms, with some gender differences: (1) excessive disengagement, reflected in HPA underactivation along with low approach motivation or high avoidance motivation; and (2) excessive engagement, reflected in HPA overactivation along with high approach motivation. This research highlights the importance of a multi-system perspective on development, suggesting that the implications of HPA dysregulation for depressive symptoms are contingent on adolescents’ tendencies toward approach versus avoidance.
Prematurity and perinatal adversity effects hypothalamic-pituitary-adrenal axis reactivity to social evaluative threat in adulthood.
Background:
This study examined the long-term effects of prematurity and perinatal adversity on individual differences in stress-related reactivity and regulation of the HPA axis. A prospective sample of 155 infants born preterm and healthy (n = 20), medical illness (n = 48), neurological illness (n = 26), and small for gestational age (n = 24) and full-term (n = 37) were recruited between 1985 and 1989. At age 23 years, multiple saliva samples were collected before and after participation in the Trier Social Stress Test and later assayed for cortisol. Results reveal that at age 23 years, infants born premature with neurological complications showed higher cortisol reactivity to social evaluative threat compared to either their full-term, small for gestation age, medically ill, or healthy preterm peers. Findings are discussed in terms of implications for contemporary theories that propose effects of early adversity on biological sensitivities and susceptibilities, which translate experience into developmental outcomes related to poor health and risk for disease.
Exposure to intimate partner violence in utero and infant internalizing behaviors: Moderation by salivary cortisol-alpha amylase asymmetry.
Background:
Guided by the main tenets of contemporary models of the developmental origins of health and disease, this study evaluated whether individual differences in reactivity of the hypothalamic-pituitary-adrenal (HPA) axis and Sympathetic Nervous System (SNS) moderate the effect of prenatal exposure to trauma on internalizing and externalizing behaviors during infancy. Participants were a community sample of 182 mothers (M age=25years, 43% Caucasian, 33% Black/African American, 24% Biracial/Other) and their infants (59% girls; M age=11.8months). Each mother completed questionnaires that assessed IPV experienced during pregnancy and also reported on her infant’s behavior problems. Infant saliva samples (later assayed for cortisol and sAA) were collected before and after a frustrating task (i.e., arm restraint). Results revealed that the association between in utero IPV and infant internalizing behaviors was most pronounced for infants with asymmetrical HPA-SNS (i.e., high-cortisol and low-sAA) reactivity to frustration, and least pronounced for infants with symmetrical HPA-SNS (i.e., low-cortisol and low-sAA or high-cortisol and high-sAA) reactivity to frustration. Higher levels of externalizing behavior, in contrast, were associated with higher levels of prenatal IPV but unrelated to either cortisol or sAA reactivity to stress. Findings replicate documented associations between maternal IPV exposure during pregnancy and offspring risk. Moreover, findings advance our understanding of individual differences in the developmental origins of health and disease and provide additional evidence that assessing multiple stress biomarkers contributes to a more comprehensive understanding of individual vulnerability to adversity.
The “yin and yang” of the adrenal and gonadal systems in elite military men.
Background:
We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the “positive coupling” hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the “yin and yang” of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.
Individual differences in the activity of the hypothalamic pituitary adrenal axis: Relations to age and cumulative risk in early childhood.
Background:
This study examined individual differences in the function of the hypothalamic-pituitary-adrenal (HPA) axis with regard to age and cumulative risk during challenging laboratory tasks administered at 6, 12, 24, and 36 months. Saliva samples were collected from a majority-minority sample of N=185 children (57% African American, 50% female) prior to and following these tasks and later assayed for cortisol. Cumulative distal risk was indexed via a composite of maternal marital status, maternal education, income-to-needs ratio, the number of children in the household, and maternal age at childbirth. Probing of hierarchical models in which cortisol levels and age were nested within child revealed significant differences in cortisol as a function of both age and cumulative risk, such that children exposed to high levels of risk exhibited higher levels of cortisol both within and across age. These results highlight the sensitivity of the HPA axis to environmental context at the level of the individual, even as that sensitivity is manifest against the background of species-typical biological development.