Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Macaca mulatta).

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

Lingering Effects of Early Institutional Rearing and Cytomegalovirus Infection on the Natural Killer Cell Repertoire of Adopted Adolescents.

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.

Behavioral inhibition in a translational nonhuman primate model: A pilot study of Kagan's behavioral inhibition paradigm modified for use in infant rhesus macaques (Macaca mulatta).

Behavioral inhibition (BI), a temperamental trait first described by Jerome Kagan, is characterized by wariness to unfamiliar persons and novel situations. BI is a moderately stable trait, with biological and genetic underpinnings. Kagan's methodology for assessing BI is widely used in humans. Although this paradigm could be readily translated for use in nonhuman primates, thereby increasing generalizability from nonhuman primates to humans and fortifying evidence that BI is evolutionarily conserved, researchers have not done so. To address this, this study utilized a modified version of Kagan's paradigm to assess behaviors and biological markers of BI in nonhuman primates. Over the first 5 weeks of life, nursery-reared rhesus monkeys (Macaca mulatta; N = 12) were rated using the standardized Infant Behavior Assessment Scale for nonhuman primates on measures related to BI (consolability, irritability, struggle, and predominant state). Three months later, behavioral assessments were made in relation to a novel playroom, an unfamiliar peer, and a variety of attention-grabbing, unfamiliar stimuli, followed by the introduction of a human stranger. Behaviors from Kagan's studies of BI in toddlers (freezing, exploration, and latency to approach) and physiological measures related to BI (heart rate) were assessed. Random effects models showed that subjects rated high in temperamental BI spent less time exploring the environment and socializing with peers and more time freezing (an indication of anxiety in rhesus monkeys). These findings suggest that Kagan's paradigm is readily adapted for use in nonhuman primates and support the utility of rhesus monkeys as translational models for assessing the causes and consequences of human BI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

COVID-19 pandemic-related trauma symptoms are associated with postpartum alcohol consumption.

OBJECTIVE: The COVID-19 pandemic has led to escalations in substance use, including alcohol consumption. Of particular concern are the potential impacts during the postpartum period, a time of heightened vulnerability to stress and potential transmission of the negative sequelae of substance use to offspring. However, postpartum alcohol consumption during the COVID-19 pandemic has not been well characterized. METHOD: Postpartum drinking habits and COVID-19-related stress were repeatedly assessed (every two weeks for 12 weeks, and at one-, six-, and 12-months postpartum) from N = 378 individuals during the COVID-19 pandemic. Average alcohol use trajectories as well as heterogeneity in trajectories were characterized. COVID-19-related trauma symptoms and coping were examined in relation to alcohol use over time. RESULTS: Average postpartum alcohol use included an initial quadratic increase from one-to-four-months postpartum, followed by a plateau between four-to-12-months. Higher (15.08%), moderate (26.90%), and lower consumption (57.90%) subgroups were identified. Endorsement of COVID-19-related trauma symptoms and using alcohol to cope with stress predicted higher consumption. CONCLUSIONS: Findings suggest a potential sensitive period in establishing postpartum alcohol use patterns from one-to-four-months postpartum. Findings further suggest that postpartum alcohol use is heterogenous and that individual response to major traumatic stressors, like the COVID-19 pandemic, may influence emerging patterns of postpartum alcohol use.

The association between food desert severity, socioeconomic status, and metabolic state during pregnancy in a prospective longitudinal cohort.

Poor metabolic health during pregnancy is associated with health concerns for pregnant individuals and their offspring. Lower socioeconomic status (SES) is one risk factor for poor metabolic health, and may be related to limited access to healthful and affordable foods (e.g., living in a food desert). This study evaluates the respective contributions of SES and food desert severity on metabolic health during pregnancy. The food desert severity of 302 pregnant individuals was determined using the United States Department of Agriculture Food Access Research Atlas. SES was measured using total household income adjusted for household size, years of education, and amount of reserve savings. Information about participants' glucose concentrations one hour following an oral glucose tolerance test during the second trimester was extracted from medical records and percent adiposity during the second trimester was assessed using air displacement plethysmography. Information about participants' nutritional intake during the second trimester was obtained by trained nutritionists via three unannounced 24-h dietary recalls. Structural equation models showed that lower SES predicted higher food desert severity (ß = - 0.20, p = 0.008) and higher adiposity (ß = - 0.27, p = 0.016) and consumption of a more pro-inflammatory diet (ß = - 0.25, p = 0.003) during the second trimester of pregnancy. Higher food desert severity also predicted higher percent adiposity during the second trimester (ß = 0.17, p = 0.013). Food desert severity significantly mediated the relationship between lower SES and higher percent adiposity during the second trimester (ßindirect = - 0.03, 95% CI [- 0.079, - 0.004]). These findings indicate that access to healthful and affordable foods is a mechanism by which SES contributes to adiposity during pregnancy and may inform interventions intended to improve metabolic health during pregnancy.

Variation in the serotonin transporter genotype is associated with maternal restraint and rejection of infants: A nonhuman primate (Macaca mulatta) model.

Studies show that maternal behaviors are mediated by the bivariate serotonin transporter (5-HTT) genotype, although the findings are mixed, with some studies showing that mothers with the s allele exhibit increased maternal sensitivity, while other studies show that mothers with the s allele show decreased maternal sensitivity. Nonhuman primate studies offer increased control over extraneous variables and may contribute to a better understanding of the effects of the 5-HTT genotype on maternal sensitivity. This study assesses the influence of 5-HTT genotype variation on maternal sensitivity in parenting in 125 rhesus macaque mothers (Macaca mulatta) during the first three-months of their infants' lives, an age well before typical infants undergo weaning. Mothers were genotyped for the 5-HTT genotype and maternal behaviors were collected, including neglectfulness, sensitivity, and premature rejections during undisturbed social interactions. Results showed that mothers homozygous for the s allele rejected their infants the most and restrained their infants the least, an indication that mothers with the s allele are more likely to neglect their infants' psychological and physical needs. These findings suggest that, at an age when an infant's needs are based on warmth, security, and protection, mothers with an s allele exhibit less sensitive maternal behaviors. High rates of rejections and low rates of restraints are behaviors that typically characterize premature weaning and are inappropriate for their infant's young age. This study is an important step in understanding the etiology of variability in maternal warmth and care, and further suggests that maternal 5-HTT genotype should be examined in studies assessing genetic influences on variation in maternal sensitivity, and ultimately, mother-infant attachment quality.

Central nervous system monoamine metabolite response to alcohol exposure is associated with future alcohol intake in a nonhuman primate model (Macaca mulatta).

It is widely held that the central monoamine neurotransmitters modulate alcohol intake. Few studies, however, directly assess the relationship between baseline and alcohol-induced monoamine turnover, as well as the change from baseline, as predictors of alcohol intake. Using a nonhuman primate model, this study investigates baseline, alcohol-induced and alcohol-induced change in monoamine activity and their relationship with alcohol intake. Alcohol-naïve, adolescent rhesus macaques (Macaca mulatta, N = 114) were administered a standardized intravenous bolus of alcohol solution (16.8%, v/v) on two occasions, approximately 1 month apart. One month prior to and 1 h following each alcohol infusion, cisternal cerebrospinal fluid (CSF) was obtained and assayed for monoamine metabolite concentrations. Approximately 6-7 months later, subjects were allowed unfettered access to an aspartame-sweetened alcohol solution (8.4%, v/v) for 1 h/day, 5 days/week, over 5-7 weeks. Results showed strong positive correlations between baseline and post-infusion CSF monoamine metabolite concentrations, indicating a trait-like response. Low baseline and post-infusion serotonin and dopamine metabolite concentrations and a smaller change in serotonin and dopamine metabolites from one infusion to the next were associated with higher alcohol intake. Low baseline and post-infusion norepinephrine metabolite concentrations predicted high alcohol intake, but unlike the other monoamines, a greater change in norepinephrine metabolite concentrations from one infusion to the next was associated with higher alcohol intake. These findings suggest that individual differences in naturally occurring and alcohol-induced monoamine activity, as well as the change between exposures, are important modulators of initial alcohol consumption and may play a role in the risk for excessive alcohol intake.

The Influence of Diet on Metabolism and Health Across the Lifespan in Nonhuman Primates.

The macro and micronutrient composition and the overall quantity of the diet are important predictors of physical and psychological health and, as a consequence, behavior. Translational preclinical models are critical to identifying the mechanisms underlying these relationships. Nonhuman primate models are particularly instrumental to this line of research as they exhibit considerable genetic, social, and physiological similarities, as well as similarities in their developmental trajectories to humans. This review aims to discuss recent contributions to the field of diet and metabolism and health using nonhuman primate models. The influence of diet composition on health and physiology across the lifespan will be the primary focus, including recent work examining the impact of maternal diet programming of offspring physiologic and behavioral developmental outcomes.

Variation in the Mu-Opioid Receptor (OPRM1) and Offspring Sex Are Associated With Maternal Behavior in Rhesus Macaques (Macaca mulatta).

A µ-opioid receptor (OPRM1) single-nucleotide-polymorphism, found in both humans and rhesus macaques mediates the mother-infant attachment bond. Because mothers treat their sons and daughters differently, it is somewhat surprising that the role of infant sex has not been assessed in the context of a maternal-OPRM1-genotype-by-infant-sex interaction. The present study investigates the effect of maternal-OPRM1-genotype and infant sex on mother-infant behaviors. Over the first 6 months of offspring life, mother-infant behavioral data assessing attachment quality was collected twice weekly from a large number of rhesus monkey mother-infant pairs (N = 161 dyads; n = 64 female infants, n = 97 male infants). Mothers were genotyped for OPRM1 variation. Factor analysis of the observed behaviors showed two factors: Attachment (maternal-infant cradling, rejections, and infant approaches and leaves), and Maternal Restraints (mother restrains infant, preventing exploration). Further analyses showed a two-way, maternal-genotype-by-infant-sex interaction for both factors. For Attachment, mothers with the CC genotype cradled and restrained (Maternal Restraints) their female infants more and rejected them less, when compared to female infants of CG mothers. Perhaps as a consequence, female infants of CC genotype mothers approached and left their mothers less often, when compared to female infants of CG mothers, likely an indication that female infants from mothers with CG genotype play a greater role in maintaining the mother-infant bond than do female infants from CC genotype mothers. This finding may also indicate a more secure attachment in infants from CC genotype mothers. Unlike female infants, on average, the mother-infant relationship of dyads with a male infant was largely undifferentiated by maternal genotype. These findings suggest that, in contrast to female infants from CG mothers, CC mothers and their female infants appear to have a closer mother-infant relationship which may portend close life-long bonds, as mothers and female offspring remain together throughout life. Male offspring appear to have a more aloof mother-infant bond regardless of OPRM1-genotype. The results of this study indicate that maternal-OPRM1 variation mediates mother-infant attachment behaviors for female infants and has less effect for male infants. This suggests that offspring sex should be included in studies investigating the effect of maternal-OPRM1 genotype on the mother-infant attachment relationship.

Race and sex differences in HDL peroxide content among American adults with and without type 2 diabetes.

BACKGROUND: High-density lipoprotein (HDL) plays a critical role in protection against atherosclerosic and cardiovascular disease (ASCVD). In addition to contributing to clearing excess vascular cholesterol, HDL particles exhibit antioxidative functions, helping to attenuate adverse effects of oxidized low-density lipoproteins. However, these beneficial properties can be undermined by oxidative stress, inflammation, and unhealthy lifestyles and diet, as well as influenced by race and sex. Thus, when assessing cardiovascular risk, it is important to consider multifactorial aspects of HDL, including antioxidant activity rather than just total amount and type of HDL-cholesterol (HDL-C) particles. Because prior research showed HDL peroxide content (HDLperox) can be inversely associated with normal anti-oxidant HDL activity, elevated HDLperox may serve as a bioindicator of HDL dysfunction. METHODS: In this study, data from a large national cohort of Americans was utilized to determine the impact of sex, race, and diabetes status on HDLperox in middle-aged and older adults. A previously developed cell-free fluorometric method was utilized to quantify HDLperox in serum depleted of apo-B containing lipoproteins. RESULTS: In keeping with predictions, white men and diabetics exhibited HDLperox in the atypical upper range, suggestive of less functional HDL. White men had higher HDLperox levels than African American males (13.46 ± 6.10 vs. 10.88 ± 5.81, p < .001). There was also a significant main effect of type 2 diabetes (F(1,1901) = 14.9, p < .0001). Overall, African Americans evinced lower HDLperox levels, despite more obesity (10.3 ± 4.7 vs.11.81 ± 5.66 for Whites) suggesting that other aspects of lipid metabolism and psychosocial factors account for the higher prevalence of ASCVD in African Americans. CONCLUSION: This research helps to provide a more comprehensive understanding of HDL function in a racially and metabolically diverse adult population. HDLperox content was significantly different in adults with type 2 diabetes, and distinctive in nondiabetic White males, and suggests other processes account for the higher prevalence of ASCVD among African Americans.

Mismatches in resident and stranger serotonin transporter genotypes lead to escalated aggression, and the target for aggression is mediated by sex differences in male and female rhesus monkeys (Macaca mulatta).

A variety of studies show that the s-allele of the serotonin transporter genotype (5-HTT) is related to aggression. However, influences of sex and 5-HTT genotype of both subject and opponent have not received as much attention in aggression research. Using a nonhuman primate model, the present study explores differences in rates of aggression exhibited by 201 group-housed male and female rhesus monkeys (Macaca mulatta; 122 females; 79 males) exposed to an unfamiliar age- and sex-matched stranger while in the presence of other same-sex members of their social group. The study also assesses whether the rates of aggression increase when the home-cage resident, the unfamiliar stimulus animal, or both possess the short (s) allele of the 5-HTT. Results showed that, when compared to females, males exhibited higher rates of physical aggression toward the stranger, and when both the male resident and the male stranger possessed the s-allele, rates of physical aggression toward the stranger increased five-fold. Resident females also engaged in higher rates of physical aggression when they possessed the s-allele, although unlike the males, their physical aggression was directed toward familiar same-sex members of their social group. The findings of this study indicate that rates of physical aggression are modulated by 5-HTT resident and stranger suggest a role of sexual competition in the phenotype of the 5-HTT genotype. Importantly, when two males with impulse deficits, as a function of the s-allele, are placed together, rates of violence exhibited by the dyad escalate substantially.

A nonhuman primate model of human non-suicidal self-injury: serotonin-transporter genotype-mediated typologies.

While non-suicidal self-injury (NSSI) occurs in the general population at a surprisingly high rate, with higher rates among certain clinical  populations, its etiology is not well-understood. Consequently, the DSM-5 lists NSSI as requiring further research. This study utilizes a translational model of naturally-occurring NSSI to assess the role of early parental neglect and variation in the serotonin transporter genotype (5-HTT) in the etiology of NSSI. Subjects (N = 161) were rhesus macaques (Macaca mulatta) reared in one of three conditions (mother-reared (MR), peer-reared (PR), or surrogate peer-reared (SPR)), and classified as NSSI (n = 18) or non-NSSI (n = 143). Subjects were genotyped for 5-HTT and their behaviors were recorded during an ecologically-meaningful, stress-evoking, intruder paradigm. Two weeks prior to testing, blood samples were obtained and assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. NSSI subjects were more likely to be SPR, paralleling human studies showing that individuals that exhibit NSSI tend to have experienced abuse or neglect early in life. Results also indicated that variation in the 5-HTT genotype differentiated the NSSI subjects. NSSI subjects that were homozygous for the L allele exhibited high plasma ACTH and high rates of stress-induced stereotypies; whereas NSSI subjects with the s allele exhibited impulsive behaviors, including frequently approaching the potentially dangerous intruder, high rates of aggressive vocal threats, and more activity. These results suggest that there may be different 5-HTT genotype-mediated NSSI typologies and that both early experiences and variation in the 5-HTT genotype may be important factors in understanding the etiology of NSSI.

Cord blood DNA methylation modifications in infants are associated with white matter microstructure in the context of prenatal maternal depression and anxiety.

Maternal and environmental factors influence brain networks and architecture via both physiological pathways and epigenetic modifications. In particular, prenatal maternal depression and anxiety symptoms appear to impact infant white matter (WM) microstructure, leading us to investigate whether epigenetic modifications (i.e., DNA methylation) contribute to these WM differences. To determine if infants of women with depression and anxiety symptoms exhibit epigenetic modifications linked to neurodevelopmental changes, 52 umbilical cord bloods (CBs) were profiled. We observed 219 differentially methylated genomic positions (DMPs; FDR p < 0.05) in CB that were associated with magnetic resonance imaging measures of WM microstructure at 1 month of age and in regions previously described to be related to maternal depression and anxiety symptoms. Genomic characterization of these associated DMPs revealed 143 unique genes with significant relationships to processes involved in neurodevelopment, GTPase activity, or the canonical Wnt signaling pathway. Separate regression models for female (n = 24) and male (n = 28) infants found 142 associated DMPs in females and 116 associated DMPs in males (nominal p value < 0.001, R > 0.5), which were annotated to 98 and 81 genes, respectively. Together, these findings suggest that umbilical CB DNA methylation levels at birth are associated with 1-month WM microstructure.

The Effects of At-Birth Adoption on Atypical Behavior and Anxiety: A Nonhuman Primate Model.

OBJECTIVE: Adopted children tend to show an increased risk for a variety of psychopathological outcomes, even when adoption occurs at birth, which some suggest is a result of nonrandom assignment of adoptees and parents. This study uses a nonhuman primate model, in which adoptions were randomly assigned, to investigate the behavioral and physiological outcomes associated with at-birth adoption. METHOD: Immediately following birth, rhesus monkey infants were randomly assigned to be reared by either their biological mother (n = 113) or by an unrelated, lactating, adoptive mother (n = 34). At 6 months of age, infant behavior and physiology were assessed during a stressful series of mother-infant separations. Four years later, stress-related behaviors were measured following confrontation by an unfamiliar intruder, an ecologically meaningful stressor. RESULTS: When compared to infants reared by their biological mothers, adopted infants exhibited more behavioral withdrawal and higher plasma adrenocorticotropic hormone (ACTH) concentrations in response to separation. These behavioral differences persisted 4 years later during a stressful intruder challenge, with adoptees exhibiting more behavioral withdrawal, stereotypies, and impulsive approaches of the potentially aggressive intruder. CONCLUSION: Compared to infants reared by their biological mothers, adopted infants exhibited more behavioral inhibition, impulsivity, and higher ACTH concentrations, even when subjects were randomly assigned to be adopted or to remain with their biological mother. To the extent that these findings generalize to humans, they suggest that the overall risk for psychopathology in adopted individuals persists even after random assignment to adoption conditions.

Early Rearing Conditions Affect Monoamine Metabolite Levels During Baseline and Periods of Social Separation Stress: A Non-human Primate Model (Macaca mulatta).

A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the "experience-expectant brain," with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. In the present study, N = 434 rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR; n = 269) or without adults with 24-h access to same-aged peers (PR; n = 165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers or peers, with each separation followed by three-day reunions with their mothers or their peers. Prior to the separation paradigm, baseline cisternal CSF samples were obtained, as well as at the end of each the four social separations, and after final separation, during a recovery period. CSF was assayed for concentrations of monoamine metabolites and a blood sample was genotyped for the serotonin transporter (5-HTT) genotype. Replicating earlier landmark findings, PR subjects with the s allele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for the L allele. MR subjects were undifferentiated by genotype. PR subjects exhibited lower CSF 5-HIAA concentrations during baseline, but higher CSF 5-HIAA during social separations, when compared to MR subjects. There were rearing effects for the dopamine metabolite homovanillic acid (HVA) and for the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), with PR subjects showing higher HVA and lower MHPG when compared to MR subjects. These findings indicate that there are long-term deficits in the response of monoamines following early maternal absence. The results of this study confirm and extend earlier findings that early parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype.

Parental genetic contributions to neonatal temperament in a nonhuman primate (Macaca mulatta) model.

Temperament is an individual's nature and is widely believed to have a heritable foundation. Few studies, however, have evaluated paternal and maternal contributions to the triadic dimensions of temperament. Rhesus monkeys are widely utilized to model genetic contributions to human development due to their close genetic-relatedness and common temperament structure, providing a powerful translational model for investigating paternal and maternal genetic influences on temperament. The temperament of rhesus monkey infants born to 19 different sires and 50 different dams was assessed during the first month of life by comparing the temperament of paternal or maternal half-siblings reared with their mothers in species-normative conditions or reared in a neonatal nursery. Factor scores from three dimensions of temperament were obtained (Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion) and ANOVAs were used to assess genetic effects. For paternal half-siblings, results showed a statistically significant paternal contribution to Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion factor scores. For maternal half-siblings, results showed a statistically significant contribution to Orienting/Regulation factor scores. When parsed by early rearing condition, results showed a paternal contribution Orienting/Regulation, Negative Affectivity, and Surgency/Extraversion scores for paternal half-siblings reared in the neonatal nursery, while there was only a paternal contribution to Surgency/Extraversion for paternal half-siblings reared by their mothers. There was only a maternal contribution to Orienting/Regulation for maternal half-siblings reared by their mothers. These results show that paternal and maternal contributions to temperament vary by environmental context, and that mothers may environmentally buffer their infants from paternal contributions to their temperament.

Stress-induced plasma cortisol concentrations in infancy are associated with later parenting behaviors in female rhesus macaques (Macaca mulatta).

Few studies have longitudinally assessed the relationship between infant stress reactivity and future parenting style. Studies show that stress-induced plasma cortisol concentrations are stable over development and that they can be utilized as a marker for stress reactivity. This study investigates the relationship between stress-induced plasma cortisol concentrations in infancy and later parenting behavior in a translational nonhuman primate model. We hypothesized that higher stress-induced cortisol levels in infancy would predict impairments in maternal behaviors in adulthood. Subjects were rhesus macaque females (N = 122; Macaca mulatta), assessed as infants and again as mothers. At 3-4 months of age, subjects underwent a standardized BioBehavioral Assessment during which blood samples were obtained and they were assessed for behaviorally inhibition. Approximately 7 years later, subjects were observed as they interacted with their own offspring for four 300-s sessions. Typical rhesus monkey mother-offspring behaviors were recorded, including approaches and leaves and maternal cradling. Results showed that subjects' stress-induced cortisol concentrations and whether they exhibited behavioral inhibition as infants predicted later maternal behavior, with high cortisol concentrations and behavioral inhibition predicting high rates of offspring approaches and leaves and low rates of maternal cradling. Results also showed that higher stress-induced cortisol concentrations in infancy predicted higher scores on the Brown Index, an indication that the subjects' offspring, rather than the subject themselves, initiated changes in proximity. Taken together, these results suggest that individuals that exhibit higher stress-induced cortisol concentrations and behavioral inhibition at 3-4 months of age are at risk for engaging in less sensitive parenting behaviors as adults. To the extent that these findings generalize to humans, they suggest an important link between stress-induced cortisol concentrations and behavioral inhibition in infancy and behavior later in life, such that early-life stress reactivity can serve as a marker for later parenting behavior.

Multi-group multi-time point confirmatory factor analysis of the triadic structure of temperament: A nonhuman primate model.

Attempts to describe the latent structure of human infant temperament have led some to suggest the existence of three major dimensions. An earlier exploratory factor analysis (EFA) supported a triadic structure of temperament in week-old rhesus monkey infants, paralleling the structure in human infants. This study sought to confirm the latent triadic structure of temperament across the first month of life in a larger sample of rhesus monkey infants (N = 668), reared by their mothers or in a neonatal nursery. A weekly behavioral assessment was obtained during the first month of life using a subset of items from the widely utilized Infant Behavioral Assessment Scale (IBAS), an instrument designed to measure temperament in infant monkeys. Using the latent constructs proposed by the earlier EFA (Orienting/Regulation, Negative Affectivity, Surgency/Extraversion), multi-group, multi-time point confirmatory factor analyses were conducted to confirm the latent temperament structure across rearing groups at each time point (weeks 1-4). Results confirm and extend those of the earlier EFA: latent Orienting/Regulation,  Negative Affectivity, and Surgency/Extraversion constructs were present across the rearing groups at each time point, with the IBAS items consistently loading onto the latent factors to a similar degree across rearing groups at each time point. These findings suggest foundational evolutionary roots for the triadic structure of human infant temperament, but that its behavioral manifestations vary across maturation and rearing condition. Similarities in latent temperament structure in humans and a representative nonhuman primate highlights the potential for utilizing translational nonhuman primate models to increase understanding of human temperament.

Masculinized Second-to-Fourth Digit Ratio (2D:4D Ratio) Is Associated With Lower Cortisol Response in Infant Female Rhesus Monkeys (Macaca mulatta).

The second-to-fourth digit ratio (2D:4D ratio) is considered a postnatal proxy measure for the degree of prenatal androgen exposure (PAE), which is the primary factor responsible for masculinizing the brain of a developing fetus. Some studies suggest that the organizational effects of PAE may extend to the hypothalamic-pituitary-adrenal (HPA) axis response to stress. This study investigates the relationship between 2D:4D ratio and HPA axis functioning using a rhesus monkey (Macaca mulatta) model. Subjects were N = 268 (180 females, 88 males) rhesus monkey infants (3-4 months of age). Plasma cortisol concentrations were assayed from two blood samples obtained during a 25-h experimental social separation stressor at 2- and 7-h post-separation. Subjects' 2D:4D ratio was measured later in life (M age = 6.70 years). It was hypothesized that infant rhesus monkeys that exhibited a more masculine-like 2D:4D ratio would show lower levels of circulating cortisol after a social separation and relocation stressor. The results showed that there was a sex difference in the left-hand 2D:4D ratio. The results also showed that there was an overall sex difference in cortisol concentrations and that female, but not male, monkeys that exhibited a more masculine-like right- and left-hand 2D:4D ratio exhibited lower mean stress-induced cortisol concentrations early in life. These findings suggest that higher levels of prenatal androgens in females, as measured by 2D:4D ratio, may be related to an attenuated HPA axis stress-response, as measured by plasma cortisol levels. To the extent that these findings generalize to humans, they suggest that the organizational effects of PAE extend to the infant HPA axis, modulating the HPA axis response, particularly in females.

Intergenerational effects of mother's early rearing experience on offspring treatment and socioemotional development.

This longitudinal study spans two generations of rhesus monkeys. First, the study investigates the effects of early rearing experiences on the maternal behavior of first-generation mothers (rates of premature infant rejection) and, second, the study investigates the effects of maternal rejection on the behavior of second-generation infants. Rhesus macaque mother-infant dyads (Macaca mulatta-N = 176) were observed twice weekly, with each session lasting 300 s. First-generation mothers were raised in one of three conditions: as mother-reared controls (MR; [n = 95]), in peer groups (PR; raised without adults but with constant access to three same-aged peers [n = 49]), or with an inanimate surrogate (SPR; raised with an inanimate fleece-covered, surrogate mother and limited daily peer-group interactions [n = 32]). Second-generation infants were all raised by their differentially reared mothers and statistically grouped into one of two groups: those that were rejected by their mothers beginning at a more-typical weaning age (controls), starting in the third month of life (n = 108), and those that were prematurely rejected, with mothers showing rejections before the third month of infant life (n = 68). Overall, PR mothers exhibited the highest rates of premature infant rejection, except for month 1 of infant life, when SPR mothers exhibited the highest rates of rejection. Intriguingly, after month 1, SPR mothers showed high rates of infant cradling and seldom rejected their infants. Independent of their mothers' early rearing environment, prematurely rejected infants displayed more aggression and passive vigilance, and were cradled and groomed less by their mothers, and there was evidence that the overall rates of rejection after the first 2 months of life had a cumulative negative effect on the developing infant. Post hoc analyses of plasma cortisol levels showed that the prematurely rejected infants had higher cortisol concentrations, suggesting a high level of stress in the prematurely rejected infants. These results suggest that maternal presence during infancy has long-term effects on a female's future maternal skills which, in turn, have intergenerational consequences for the socioemotional development of second-generation infants.