Camelia E. Hostinar

Psychobiological Mechanisms Underlying the Social Buffering of the Hypothalamic-Pituitary-Adrenocortical Axis: A Review of Animal Models and Human Studies Across Development

Discovering the stress-buffering effects of social relationships has been one of the major findings in psychobiology in the last century. However, an understanding of the underlying neurobiological and psychological mechanisms of this buffering is only beginning to emerge. An important avenue of this research concerns the neurocircuitry that can regulate the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. The present review is a translational effort aimed at integrating animal models and human studies of the social regulation of the HPA axis from infancy to adulthood, specifically focusing on the process that has been named social buffering. This process has been noted across species and consists of a dampened HPA axis stress response to threat or challenge that occurs with the presence or assistance of a conspecific. We describe aspects of the relevant underlying neurobiology when enough information exists and expose major gaps in our understanding across all domains of the literatures we aimed to integrate. We provide a working conceptual model focused on the role of oxytocinergic systems and prefrontal neural networks as 2 of the putative biological mediators of this process, and propose that the role of early experiences is critical in shaping later social buffering effects. This synthesis points to both general future directions and specific experiments that need to be conducted to build a more comprehensive model of the HPA social buffering effect across the life span that incorporates multiple levels of analysis: neuroendocrine, behavioral, and social.

Associations between early life adversity and executive function in children adopted internationally from orphanages

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.

Future Directions in the Study of Social Relationships as Regulators of the HPA Axis across Development

Many promising findings support the notion that social relationships can dampen hypothalamic-pituitary-adrenocortical (HPA) axis stress responses and protect individuals from maladaptive psychological and physical disease states. Despite the public health relevance of this topic, little is known about developmental changes in the social regulation of the HPA system, with most prior research having focused on early childhood and adulthood. This gap is particularly striking with regards to adolescence, an age period when it seems likely that reliance on parents as sources of stress-buffering decreases, even as the security of friends and relationship partners as stress buffers may not yet be certain. Furthermore, we speculate that early life stress or abnormal social experiences may impact the propensity to draw mental and physical health benefits from social relationships, but more empirical support for these ideas is needed. Last, research linking social support to cumulative life stress has mostly relied on self-report measures of stress, making it difficult to show that social support impacts the type of chronic stress exposure that is associated with increased allostatic load or “wear and tear” on the body and on psychological functioning. Recent advancements in methodology (e.g., assessing hair cortisol levels) as well as composite measures of allostatic load using biomarkers that capture the activity of multiple neuroendocrine, cardiovascular, immune, and metabolic systems will allow us to ask new questions about the extent to which social relationships can impact cumulative life stress and health.

The Developmental Effects of Early Life Stress An Overview of Current Theoretical Frameworks

The field of psychobiology has two major theories for talking about stress and health: the allostatic load model, which grew out of biological and neuroscience approaches to understanding health and disease, and the adaptive calibration model, which developed out of an explicitly evolutionary-developmental framework. Both are based on assumptions that the brain coordinates a distributed and dynamic set of neural circuits that regulate behavior and stress physiology to help the organism adapt to the demands of the environment. Both models support the notion that experiences early in life are embedded into the regulation of stress systems in ways that shape the organism’s future responses. These two paradigms differ in their emphasis on whether changes in how stress systems function are viewed as adaptive or maladaptive. The goal of this review is to identify the strengths and weaknesses of each framework and to discuss some implications for future studies and for policy.

Parent support is less effective in buffering cortisol stress reactivity for adolescents compared to children.

The goal of the present study was to investigate developmental differences in the effectiveness of parent support to alleviate hypothalamic-pituitary-adrenal (HPA) axis stress responses of children (ages 9-10, N = 40) and adolescents (ages 15-16, N = 41). We experimentally manipulated the provision of parent support during the speech preparation period before a modified Trier Social Stress Test (TSST) and examined its effect on levels of salivary cortisol secreted in response to this laboratory stressor. Analyses revealed a significant interaction of condition and age group such that social support from the parent (versus a stranger) significantly eliminated the cortisol stress response in children, but had no effect on the response among adolescents.

Oxytocin receptor gene polymorphism, perceived social support, and psychological symptoms in maltreated adolescents

Despite the detrimental consequences of child maltreatment on developmental processes, some individuals show remarkable resilience, with few signs of psychopathology, while others succumb to dysfunction. Given that oxytocin has been shown to be involved in social affiliation, attachment, social support, trust, empathy, and other social or reproductive behaviors, we chose to examine the possible moderation of maltreatment effects on perceived social support and on psychological symptoms by a common single nucleotide polymorphism (rs53576) in the oxytocin receptor gene. We studied adolescents (N = 425) aged approximately 13-15, including participants with objectively documented maltreatment histories (N = 263) and a nonmaltreated comparison group from a comparable low socioeconomic status background (N = 162). There was a significant genotype by maltreatment interaction, such that maltreated adolescents with the G/G genotype perceived significantly lower social support compared to maltreated A-carriers, with no effect of genotype in the comparison group. Maltreated G/Gs also reported higher levels of internalizing symptoms than did A-carriers, even though they did not differ from them on objective measures of maltreatment (type, duration, or severity). G/G homozygotes may be more attuned to negative social experiences, such as family maltreatment, while maltreated A-carriers were indistinguishable from nonmaltreated adolescents in levels of mental health symptoms.

Social deprivation and the HPA axis in early development

Growing evidence suggests that early social deprivation impacts the activity of the hypothalamic-pituitary-adrenocortical axis. Early adverse care in the form of institutional or orphanage care provides a human model for early social deprivation. The present study examined changes in diurnal cortisol during the transition to family care in the first 2 years post-adoption. Children adopted between 15 and 36 months from institutional care were examined four times during their first 2 years post-adoption (N=58). Comparison groups included same-aged peers reared in their birth families (N=50) and children adopted during their first year from overseas foster care (N=47). Children provided daily cortisol samples at roughly 2, 9, 17, and 25 months post-adoption. Post-institutionalized and post-foster care children exhibited less steep diurnal cortisol compared to non-adopted same-aged peers; these differences did not diminish across the 2 year period. For post-institutionalized children, lower social care quality in institutions was associated with less steep cortisol slopes. Lastly, shallower diurnal cortisol was a mediator between adoption status and increased behavioral problems 2 years post-adoption. Consistent with the non-human primate literature, early social deprivation may contribute to early programming of the HPA axis.

Parental buffering of fear and stress neurobiology: Reviewing parallels across rodent, monkey, and human models.

It has been long recognized that parents exert profound influences on child development. Dating back to at least the seventeenth-century Enlightenment, the ability for parents to shape child behavior in an enduring way has been noted. Twentieth-century scholars developed theories to explain how parenting histories influence psychological development, and since that time, the number of scientific publications on parenting influences in both human and nonhuman animal fields has grown at an exponential rate, reaching numbers in the thousands by 2015. This special issue describes a symposium delivered by Megan Gunnar, Regina Sullivan, Mar Sanchez, and Nim Tottenham in the Fall of 2014 at the Society for Social Neuroscience. The goal of the symposium was to describe the emerging knowledge on neurobiological mechanisms that mediate parent–offspring interactions across three different species: rodent, monkey, and human. The talks were aimed at designing testable models of parenting effects on the development of emotional and stress regulation. Specifically, the symposium aimed at characterizing the special modulatory (buffering) effects of parental cues on fear- and stress-relevant neurobiology and behaviors of the offspring and to discuss examples of impaired buffering when the parent–infant relationship is disrupted.

Alterations in stress responses of the hypothalamic-pituitary-adrenal axis in small for gestational age infants

Mounting epidemiologic evidence and animal models suggest that stressful conditions during the intrauterine period may increase susceptibility to several adult conditions, including metabolic syndrome, cardiovascular disease, and psychiatric disorders. Increased cortisol levels due to alterations in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis are believed to be one mediating mechanism. Infants born after significant exposure to stressful conditions are often small for gestational age (SGA) based on standardized growth norms. Lifelong programming of the HPA axis has been proposed as a mechanism to explain the association between SGA infants and adult disease. However, few studies have measured HPA axis function proximal to birth as done in this study of SGA infants during the first week of life. Participants included 37 infants in two groups based on birth size (gestational age range: 34-41weeks). SGA infants were <10th percentile for age (n=21) and appropriate for gestational age (AGA) infants (n=16) were from 20 to 90th percentile for age. Cortisol response to a heel lance for blood collection was measured for all infants. Hierarchical Linear Modeling was used to test the effect of AGA/SGA group status on cortisol trajectories in response to the stressor. Group was a significant predictor of quadratic slopes (t=2.84, χ(2)=8.19, p=.004) after controlling for the effect of group on intercepts and linear slopes. Predicted growth curves for ln-cortisol were plotted for each group based on regression coefficients. The predicted curves capture the significant group difference in trajectories, as well as the blunted response for the SGA group and the robust peak in cortisol production in response to the stressor for the AGA group. This evidence suggests SGA neonates have blunted HPA axis responses to stressors in comparison to AGA infants. These findings are consistent with animal models showing that adverse intrauterine conditions can result in blunted cortisol responses to acute stressors and may provide a mechanism for adult susceptibility to disease for individuals that are SGA at birth.

The Social Buffering of the Hypothalamic-Pituitary-Adrenocortical Axis in Humans: Developmental and Experiential Determinants

Social buffering, a subset of social support, is the process through which the availability of a conspecific reduces the activity of stress-mediating neurobiological systems. While its role in coping and resilience is significant, we know little about its developmental history in humans. This brief review presents an integrative developmental account of the social buffering of hypothalamic–pituitary–adrenocortical (HPA) stress reactivity in humans, from infancy to adulthood. During infancy, parents are powerful stress-regulators for children, but child temperament also plays a role and interacts with parenting quality to predict the magnitude of stress responses to fear or pain stimuli. Recent work indicates that parental support remains a potent stress buffer into late childhood, but that it loses its effectiveness as a buffer of the HPA axis by adolescence. Puberty may be the switch that alters the potency of parental buffering. Beginning in middle childhood, friends may serve as stress buffers, particularly when other peers are the source of stress. By adulthood, romantic partners assume this protective role, though studies often reveal sex differences that are currently not well understood. Translational research across species will be critical for developing a mechanistic understanding of social buffering and the processes involved in developmental changes noted in this review.