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.

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).

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.

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.

Synthesis and interface characterization of CNTs on graphene.

Carbon nanotubes (CNTs) and graphene are potential candidates for future interconnect materials. CNTs are promising on-chip via interconnect materials due to their readily formed vertical structures, their current-carrying capacity, which is much larger than existing on-chip interconnect materials such as copper and tungsten, and their demonstrated ability to grow in patterned vias with sub-50 nm widths; meanwhile, graphene is suitable for horizontal interconnects. However, they both present the challenge of having high-resistance contacts with other conductors. An all-carbon structure is proposed in this paper, which can be formed using the same chemical vapor deposition method for both CNTs and graphene. Vertically aligned CNTs are grown directly on graphene with an Fe or Ni catalyst. The structural characteristics of the graphene and the grown CNTs are analyzed using Raman spectroscopy and electron microscopy techniques. The CNT-graphene interface is studied in detail using transmission electron microscopic analysis of the CNT-graphene heterostructure, which suggests C-C bonding between the two materials. Electrical measurement results confirm the existence of both a lateral conduction path within graphene and a vertical conduction path in the CNT-graphene heterostructure, giving further support to the C-C bonding at the CNT-graphene interface and resulting in potential applications for all-carbon interconnects.