Davide Ponzi

Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation.

Exposure to bisphenol A (BPA) is implicated in many aspects of metabolic disease in humans and experimental animals. We fed pregnant CD-1 mice BPA at doses ranging from 5 to 50,000μg/kg/day, spanning 10-fold below the reference dose to 10-fold above the currently predicted no adverse effect level (NOAEL). At BPA doses below the NOAEL that resulted in average unconjugated BPA between 2 and 200pg/ml in fetal serum (AUC0-24h), we observed significant effects in adult male offspring: an age-related change in food intake, an increase in body weight and liver weight, abdominal adipocyte mass, number and volume, and in serum leptin and insulin, but a decrease in serum adiponectin and in glucose tolerance. For most of these outcomes non-monotonic dose-response relationships were observed; the highest BPA dose did not produce a significant effect for any outcome. A 0.1-μg/kg/day dose of DES resulted in some but not all low-dose BPA outcomes.

Evolutionary functions of early social modulation of hypothalamic-pituitary-adrenal axis development in humans.

The hypothalamic-pituitary-adrenal axis (HPAA) is highly responsive to social challenges. Because stress hormones can have negative developmental and health consequences, this presents an evolutionary paradox: Why would natural selection have favored mechanisms that elevate stress hormone levels in response to psychosocial stimuli? Here we review the hypothesis that large brains, an extended childhood and intensive family care in humans are adaptations resulting from selective forces exerted by the increasingly complex and dynamic social and cultural environment that co-evolved with these traits. Variations in the modulation of stress responses mediated by specific HPAA characteristics (e.g., baseline cortisol levels, and changes in cortisol levels in response to challenges) are viewed as phenotypically plastic, ontogenetic responses to specific environmental signals. From this perspective, we discuss relations between physiological stress responses and life history trajectories, particularly the development of social competencies. We present brief summaries of data on hormones, indicators of morbidity and social environments from our long-term, naturalistic studies in both Guatemala and Dominica. Results indicate that difficult family environments and traumatic social events are associated with temporal elevations of cortisol, suppressed reproductive functioning and elevated morbidity. The long-term effects of traumatic early experiences on cortisol profiles are complex and indicate domain-specific effects, with normal recovery from physical stressors, but some heightened response to negative-affect social challenges. We consider these results to be consistent with the hypothesis that developmental programming of the HPAA and other neuroendocrine systems associated with stress responses may facilitate cognitive targeting of salient social challenges in specific environments.

Hormonal Mechanisms for Regulation of Aggression in Human Coalitions

Coalitions and alliances are core aspects of human behavior. All societies recognize alliances among communities, usually based in part on kinship and marriage. Aggression between groups is ubiquitous, often deadly, fueled by revenge, and can have devastating effects on general human welfare. Given its significance, it is surprising how little we know about the neurobiological and hormonal mechanisms that underpin human coalitionary behavior. Here we first briefly review a model of human coalitionary behavior based on a process of runaway social selection. We then present several exploratory analyses of neuroendocrine responses to coalitionary social events in a rural Dominican community, with the objective of understanding differences between in-group and out-group competition in adult and adolescent males. Our analyses indicate: (1) adult and adolescent males do not elevate testosterone when they defeat their friends, but they do elevate testosterone when they defeat outsiders; (2) pre-competition testosterone and cortisol levels are negatively associated with strength of coalitionary ties; and (3) adult males usually elevate testosterone when interacting with adult women who are potential mates, but in a striking reversal, they have lower testosterone if the woman is a conjugal partner of a close friend. These naturalistic studies hint that reciprocity, dampening of aggression, and competition among friends and allies may be biologically embedded in unique ways among humans.

Co-ruminating increases stress hormone levels in women

Same-sex friendships are an important source of social support and typically contribute to positive adjustment. However, there can be adjustment trade-offs if the friends co-ruminate (i.e., talk excessively about problems) in that co-rumination is related to having close friendships but also to increased internalizing symptoms. The current study utilized an experimental manipulation that elicited co-rumination in young women and thus mirrored an everyday response to stress. Observed co-rumination was associated with a significant increase in the stress hormone, cortisol (after controlling for self-reported co-rumination and for cortisol levels assessed before the discussion of problems). These findings suggest that co-rumination can amplify, rather than mitigate, the hormonal stress response to personal life stressors.

Non-monotonic dose effects of in utero exposure to di(2-ethylhexyl) phthalate (DEHP) on testicular and serum testosterone and anogenital distance in male mouse fetuses

Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant. Epidemiological studies suggest that DEHP decreases masculinization of male fetuses. Numerous rat studies report DEHP reduces fetal testosterone production at doses greatly exceeding human exposure. We fed pregnant CD-1 mice 0.5-500,000 μg/kg/day DEHP from gestation day (GD) 9-18 and examined mothers and male fetuses on GD 18. We assessed non-monotonic dose-response by adding a quadratic term to a simple linear regression model. Except at the 500,000 μg/kg/day dose, DEHP stimulated an increase in maternal and fetal serum testosterone and increased anogenital distance (AGD). Non-monotonic dose-response curves were noted for AGD and maternal, and testis testosterone (P values 0.013-0.021). Because data from our highest dose (500,000 μg/kg/day) did not differ significantly from controls, this dose could have been incorrectly assumed to be the NOAEL had we only tested very high doses, as is typical in studies for regulatory agencies.

Eveningness is associated with higher risk-taking, independent of sex and personality

This study tested the hypotheses that eveningness is associated with higher risk-taking propensities across different domains of risk and that this association is not the result of sex differences or confounding covariation with particular personality traits. Study participants were 172 men and women between 20 and 40 years of age. Surveys assessed chronotype, domain-specific risk-taking and risk-perception, and Big Five personality dimensions. Eveningness was associated with greater general risk-taking in the specific domains of financial, ethical, and recreational decision making. Although risk-taking was associated with both risk perception and some personality dimensions, eveningness predicted risk-taking independent of these factors. Higher risk-taking propensities among evening types may be causally or functionally linked to their propensities for sensation- and novelty-seeking, impulsivity, and sexual promiscuity.

Evolution of neuroendocrine mechanisms linking attachment and life history : The social neuroendocrinology of middle childhood

An extended period of childhood and juvenility is a distinctive aspect of human life history. This stage appears to be important for learning cultural, social, and ecological skills that help prepare the child for the adult socio-competitive environment. The unusual pattern of adrenarche in humans (and chimpanzees) may facilitate adaptive modification of the neurobiological mechanisms that underpin reproductive strategies. Longitudinal monitoring of DHEA/S in naturalistic context could provide important new insights into these aspects of child development.

Interest in Babies Negatively Predicts Testosterone Responses to Sexual Visual Stimuli Among Heterosexual Young Men

Men’s testosterone may be an important physiological mechanism mediating motivational and behavioral aspects of the mating/parenting trade-off not only over time but also in terms of stable differences between mating-oriented and parenting-oriented individuals. In this study, we tested the hypothesis that self-reported interest in babies is inversely related to testosterone reactivity to cues of short-term mating among heterosexual young men. Among 100 participants, interest in babies was related to a slow life-history strategy, as assessed by the Mini-K questionnaire, and negatively related to testosterone responses to an erotic video. Interest in babies was not associated with baseline testosterone levels or with testosterone reactivity to nonsexual social stimuli. These results provide the first evidence that differential testosterone reactivity to sexual stimuli may be an important aspect of individual differences in life-history strategies among human males.

Hormones in the Wild: Monitoring the Endocrinology of Family Relationships

SYNOPSIS For the past 23 years we have conducted a field study of child stress and family environment in Bwa Mawego, Dominica. Our primary objectives were to document hormonal responses of children to everyday interactions with their parents and other care providers, concomitant with longitudinal assessment of developmental and health outcomes. Here we provide a brief summary of our research design and highlight a few results from this collaborative, interdisciplinary project.

Cortisol, salivary alpha-amylase and children’s perceptions of their social networks

In recent years there has been a growing interest in the use of social network analysis in biobehavioral research. Despite the well-established importance of social relationships in influencing human behavior and health, little is known about how children’s perception of their immediate social relationships correlates with biological parameters of stress. In this study we explore the association between two measures of children’s personal social networks, perceived network size and perceived network density, with two biomarkers of stress, cortisol and salivary alpha-amylase. Forty children (mean age = 8.30, min age = 5, and max age = 12) were interviewed to collect information about their friendships and three samples of saliva were collected. Our results show that children characterized by a lower pre-interview cortisol concentration and a lower salivary alpha-amylase reactivity to the interview reported the highest density of friendships. We discuss this result in light of the multisystem approach to the study of children’s behavioral outcomes, emphasizing that future work of this kind is needed in order to understand the cognitive and biological mechanisms underlying children’s and adolescents’ social perceptual biases.