Megan R. Gunnar

Adversity experienced in early life can have detrimental effects on physical and mental health. One pathway in which these effects occur is through the hypothalamic-pituitary-adrenal (HPA) axis, a key physiological stress-mediating system. In this review, we discuss the theoretical perspectives that guide stress reactivity and regulation research, the anatomy and physiology of the axis, developmental changes in the axis and its regulation, brain systems regulating stress, the role of genetic and epigenetics variation in axis development, sensitive periods in stress system calibration, the social regulation of stress (i.e., social buffering), and emerging research areas in the study of stress physiology and development. Understanding the development of stress reactivity and regulation is crucial for uncovering how early adverse experiences influence mental and physical health.

Early life stress (ELS) is linked to an elevated risk of poor health and early mortality, with emerging evidence pointing to the pivotal role of the immune system in long-term health outcomes. While recent research has focused on the impact of ELS on inflammation, this study examined the impact of ELS on immune function, including CMV seropositivity, inflammatory cytokines, and lymphocyte cell subsets in an adolescent cohort. This study used data from the Early Life Stress and Cardiometabolic Health in Adolescence Study (N = 191, aged 12 to 21 years, N = 95 exposed to ELS). We employed multiple regression to investigate the association between ELS, characterized by early institutional care, cytomegalovirus (CMV) seropositivity (determined by chemiluminescent immunoassay), inflammation (CRP, IL-6, and TNF-a determined by ELISA), and twenty-one immune cell subsets characterized by flow cytometry (sixteen T cell subsets and five B cell subsets). Results reveal a significant association between ELS and lymphocytes that was independent of the association between ELS and inflammation: ELS was associated with increased effector memory helper T cells, effector memory cytotoxic T cells, senescent T cells, senescent B cells, and IgD− memory B cells compared to non-adopted youth. ELS was also associated with reduced percentages of helper T cells and naive cytotoxic T cells. Exploratory analyses found that the association between ELS and fewer helper T cells and increased cytotoxic T cells remained even in cytomegalovirus (CMV) seronegative youth. These findings suggest that ELS is associated with cell subsets that are linked …

BackgroundIron deficiency anemia (IDA) affects up to 30% of pregnant women worldwide, with a higher risk among low-income and racially- and ethnically-minoritized women. IDA during pregnancy can lead to adverse outcomes for both the mother and the infant, including long-term impacts on brain and immune development. Previous research in animals and humans has found an association between psychological stress and offspring iron status, potentially through nutrient metabolism disruption from dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis. However, no study has investigated the association between HPA axis biology and iron status in pregnancy.MethodsAt four points in pregnancy (16, 24, 30, & 36 weeks gestation), 168 pregnant Black women with Medicaid insurance completed a laboratory assessment during which salivary cortisol was used to measure HPA axis stress …

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56bright NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56dim lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.

This editorial argues that research findings in child and adolescent psychopathology need to be contextualized with demographic information and location in order to help with interpretation of findings and implications for the services that are available and/or potentially effective. For developmental psychopathology and child and adolescent mental health treatment, the demographic information should include key factors known to influence etiology, treatment effectiveness and service availability. These factors include, but may not be limited to, sex and age, location including country (and city or urban area), socioeconomic class, culture and minoritized status. Including such information, in addition to helping us understand why findings might not generalize, can draw attention to the exclusion of certain groups from research and so drive attempts to increase the representativeness of research in child and adolescent …

Objective To prospectively evaluate the relationship between cumulative environmental stress and cardiometabolic risk in middle childhood, and to examine whether hair cortisol, a measure of hypothalamic pituitary adrenal‐axis activity, mediates this relationship. Methods In a cohort of children from low‐income households (n = 320; 59% Hispanic, 23% Black, body mass index (BMI) percentile >50th at enrollment), environmental stressors including family and neighbourhood factors representing disadvantage/deprivation, and cortisol concentrations from hair samples, were measured over five timepoints beginning when children were 2–4 years old. Cardiometabolic risk factors (i.e., BMI, blood pressure, lipids, blood sugar, C‐reactive protein) were measured at the final timepoint when children were 7–11 years of age. Results In adjusted logistic regression models, greater cumulative environmental stress …

Adolescence is a developmental period of both heightened opportunity and risk (Thapar et al., 2012). Adolescents become increasingly sensitive to peer evaluation and thus more vulnerable to social evaluative threat, while at the same time their stress response systems becomes more reactive (Sumter et al., 2010; van den Bos et al., 2014). The hypothalamic-pituitary-adrenal (HPA) axis is a critical stress-responsive neuroendocrine system that produces the hormone, cortisol. HPA axis activity both supports allostasis, or the capacity to withstand stressors, and also shapes brain systems involved in threat detection and regulation (Gunnar, 2017). Although the threat of social evaluation is a major source of stress activation, the support of social partners, termed social buffering, can provide protection from stress (Gunnar, 2017). Parents play a powerful role in buffering their children’s stress; however, parental social buffering potency diminishes over the pubertal transition (Doom et al., 2015; Hostinar et al., 2015). Given the diminishing of parental social buffering efficacy over the pubertal transition, is it important to know whether other salient figures in an adolescent’s life, such as close friends, take over the job as stress buffers? Doom, Doyle, and Gunnar (2017) tested whether friends acted as social buffers during the adolescent period by having children and adolescent participants prepare for a speech, which was a part of a socially evaluative stressor (Trier Social Stress Test, Birkett, 2011), with either their parent or a same-sexed best friend. They found that for adolescents (15-16 years), but not children (9-10 years), having a same-sexed best …

BackgroundPsychosocial stress has been positively associated with sleep difficulties. We wondered whether stress during the COVID-19 pandemic would have a negative effect on insomnia in adolescents and whether this relationship would be moderated by virtual interaction with friends via social media and text messages, given previous evidence on friends being stress buffers for adolescents.MethodsIn the present study, we collected self-reported frequency of insomnia (i.e., having an extremely hard time falling asleep), the stress level during the COVID-19 pandemic, and the experience of using social media and text messages to interact with friends from 138 healthy adolescents/young adults (62 females) aged 12-21.4 years (Mage=15.42 years, SDage=2.31 years).ResultsA multiple regression model revealed a significant main effect of stress (B= 0.57, p<.01), sex (B=0.45, p<.05) and an interaction effect of …