Parental experience is linked with lower vasopressin receptor 1a binding and decreased postpartum androgens in titi monkeys.

Parenting induces many neurological and behavioral changes that enable parents to rear offspring. Vasopressin plays an important role in this process via its effects on cognition, affect, and neuroplasticity, and in some cases, via interactions with decreased parental androgens. Thus far, the role of these hormones has been primarily studied in rodents.

Biobehavioral organization shapes the immune epigenome in infant rhesus Macaques (Macaca mulatta).

How individuals respond to and cope with stress is linked with their health and well-being. It is presumed that early stress responsiveness helps shape the health of the developing organism, but the relationship between stress responsiveness and early immune function during development is not well-known. We hypothesized that stress responsiveness may shape epigenetic regulation of immune genes in infancy.

Infant inhibited temperament in primates predicts adult behavior, is heritable, and is associated with anxiety-relevant genetic variation.

An anxious or inhibited temperament (IT) early in life is a major risk factor for the later development of stress-related psychopathology. Starting in infancy, nonhuman primates, like humans, begin to reveal their temperament when exposed to novel situations. Here, in Study 1 we demonstrate this infant IT predicts adult behavior.

Prenatal Relocation Stress Enhances Resilience Under Challenge in Infant Rhesus Macaques.

The prenatal period is a developmental stage of peak sensitivity, during which environmental exposures can program post-natal developmental outcomes. Prenatal stress, in particular, has often been associated with detrimental neurobehavioral outcomes like mood and anxiety disorders. In the present study, we examined the effects of a stressful prenatal maternal experience (maternal relocation during pregnancy) on the post-partum development of offspring in rhesus macaques.

Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility.

The rhesus macaque () is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization.

Oxytocin receptor binding in the titi monkey hippocampal formation is associated with parental status and partner affiliation.

Social cognition is facilitated by oxytocin receptors (OXTR) in the hippocampus, a brain region that changes dynamically with pregnancy, parturition, and parenting experience. We investigated the impact of parenthood on hippocampal OXTR in male and female titi monkeys, a pair-bonding primate species that exhibits biparental care of offspring. We hypothesized that in postmortem brain tissue, OXTR binding in the hippocampal formation would differ between parents and non-parents, and that OXTR density would correlate with frequencies of observed parenting and affiliative behaviors between partners.

Behavioral mimicry predicts social favor in adolescent rhesus macaques (Macaca mulatta).

Non-conscious mimicry is a highly conserved component of animal behavior with multifaceted connections to sociality across taxa. One intriguing consequence of this mimicry in primates is that it promotes positive social feedback from the recipient toward the mimicker. This suggests that mimicry in primates may be an important aspect of positive social interaction, but few studies have tracked the consequences of mimicry in naturally occurring complex social conditions.

Early Social Stress Promotes Inflammation and Disease Risk in Rhesus Monkeys.

Early social stress has potent lifelong health effects. We examined the association of early stress in the attachment relationship (low maternal sensitivity, low MS), lower maternal social hierarchy rank, and greater frequency of group-level social conflict, with biomarkers of inflammatory stress response in plasma (IL-8, MCP-1 and CRP collected two hours after temporary separation from mothers and social groups) and risk for developing a common macaques disease outcome (infectious colitis) in 170 socially-housed rhesus monkeys. We controlled for gene-environment correlations by comparing cross-fostered subjects with infants reared by their biological mothers.

Genetic and environmental factors in the intergenerational transmission of maternal care in rhesus macaques: Preliminary findings.

Early life experiences reorganize the brain and behavior of the developing infant, often with lifelong consequences. There is perhaps no more potent developmental influence than the quality of parental care: it is an experience common to all mammals, and its effects have been observed across species. The effects of parental care can be particularly difficult to abolish, as levels of care are often perpetuated across generations.

Paternal line effects of early experiences persist across three generations in rhesus macaques.

The effects of early stress may not be limited to the exposed generation, but are sometimes passed on to subsequent generations. Such non-genetic transgenerational inheritance is a potentially important developmental and evolutionary force. We compared the transgenerational effects of maternal and paternal line early stress on anxiety- and health-related traits in three non-exposed generations (F1, F2 and F3) of semi-naturalistically raised rhesus macaques.

Paternal early experiences influence infant development through non-social mechanisms in Rhesus Macaques.

Background: Early experiences influence the developing organism, with lifelong and potentially adaptive consequences. It has recently become clear that the effects of early experiences are not limited to the exposed generation, but can influence physiological and behavioral traits in the next generation. Mechanisms of transgenerational effects of parental early experiences on offspring development are often attributed to prenatal or postnatal parental influence, but recent data suggest that germ-line plasticity may also play a role in the transgenerational effects of early experiences.

Epigenetic plasticity following early stress predicts long-term health outcomes in rhesus macaques.

Early life stress has been linked with poorer lifelong health outcomes across species, including modern and ancient humans. Epigenetic mechanisms, such as DNA methylation patterning of stress pathway genes in stress-responsive tissue, may play an important role in the long-term health effects of early stress across species. The relationships among early maternal care quality, DNA methylation patterns in a candidate stress pathway gene (serotonin transporter, 5-HTT) linked region in blood DNA, and adult health outcomes were examined in male and female rhesus macaques, excellent models of human health.

Transgenerational effects of variable foraging demand stress in female bonnet macaques.

Stress coping is an important part of mammalian life, influencing somatic and mental health, social integration, and reproductive success. The experience of early psychological stress helps shape lifelong stress coping strategies. Recent studies have shown that the effects of early stress may not be restricted to the affected generation, but may also be transmitted to offspring.

Enhancing genotyping of MAOA-LPR and 5-HTT-LPR in rhesus macaques (Macaca mulatta).

Background: Genetic variation in monoamine oxidase A (MAOA) and serotonin transporter (5-HTT)-linked polymorphic regions (LPR) is associated with neuropsychiatric behavior.

Methods: We genotyped 37 macaques using conventional PCR product gel fractionation and by capillary electrophoresis of multiplexed amplicons and compared the data.

Results: Genotype concordance was 97% and 95% for MAOA-LPR and 5-HTT-LPR, respectively.

DNA methylation as a risk factor in the effects of early life stress.

Epigenetic marks (e.g., DNA 5-methylcytosine [5mC] content or CpG methylation) within specific gene regulatory regions have been demonstrated to play diverse roles in stress adaptation and resulting health trajectories following early adversity.

Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques.

Epigenetic mechanisms may moderate genetic and environmental risk (GxE) for mood disorders. We used an experimental rhesus macaque model of early life stress to test whether epigenetic regulation of serotonin transporter (5-HTT) may contribute to GxE interactions that influence behavior and emotion. We hypothesized that peripheral blood mononuclear cell (PBMC) DNA methylation within an 800 bp cytosine-phosphate-guanosine (CpG) island that overlaps with the 5-HTT transcription initiation start site, a hypothesized model of the same genomic region in brain tissue, would mediate or moderate the effects of early life stress and a functional 5-HTT promoter polymorphism (rh5-HTTLPR) on two outcomes: PBMC 5-HTT expression and behavioral stress reactivity.

Serotonin pathway gene-gene and gene-environment interactions influence behavioral stress response in infant rhesus macaques.

A subset of serotonin (5-HT) pathway polymorphisms has been shown to confer risk for psychological dysfunction, particularly in individuals who experience early adversity. Understanding the developmental processes underlying these Gene x Environment interactions will strengthen the search for risk factors for behavioral dysfunction. We investigated the combined influence of two serotonin pathway polymorphisms and species-atypical, and possibly adverse, rearing (nursery rearing [NR]) on two dimensions of behavioral stress response in infant rhesus macaques.

Serotonin transporter expression is predicted by early life stress and is associated with disinhibited behavior in infant rhesus macaques.

Serotonin transporter (5-HTT) expression patterns may contribute to the risk for adverse psychological outcomes following early life stress. The present study investigated whether two types of early life stress, maternal and social aggression, and a serotonin transporter gene promoter polymorphism (rh5-HTTLPR) predicted lower post-stressor peripheral blood mononuclear cell (PBMC) 5-HTT expression in infant rhesus macaques. We further probed the relationships among these factors and infant behavioral disinhibition within a stressful situation.

Parental care moderates the influence of MAOA-uVNTR genotype and childhood stressors on trait impulsivity and aggression in adult women.

Objectives: Adverse childhood experiences are associated with poor mental health outcomes, including vulnerability to mood disorders and/or antisocial behavior. A functional polymorphism in the regulatory region of the monoamine oxidase A gene (monoamine oxidase A untranslated variable nucleotide tandem repeat, MAOA-uVNTR) may moderate the degree of risk conferred by early trauma. Experiential factors may mitigate or exacerbate the effects of trauma on individuals at genetic risk.

Reported childhood abuse is associated with low serotonin transporter binding in vivo in major depressive disorder.

Background: Physical or psychological adversity in childhood is associated with a higher risk for depression in adulthood, and with persistent serotonergic abnormalities in humans and in animal models. We hypothesized that reported childhood abuse would be associated with lower brain serotonin transporter (5-HTT) binding potential (BP(P), proportional to the number of available transporters) in adults. We examined healthy volunteers and subjects with major depressive disorder, a sample enriched for childhood abuse.

What is an "adverse" environment? Interactions of rearing experiences and MAOA genotype in rhesus monkeys.

Background: Studies have been inconsistent in demonstrating that early adversity and specific genotype can be joint risk factors for poor behavioral outcomes. Using a rhesus monkey model, we examined how social context and different forms of early adversity influence whether a specific genotype (polymorphism in the promoter region of monoamine oxidase A [MAOA]) affects display of aggressive, fearful, and anxious behaviors.

Methods: Rhesus monkey infants (n = 473) were exposed to brief social challenge at age 3-4 months.

Dimensions of response to novelty are associated with social engagement and aggression in adult male rhesus macaques (Macaca mulatta).

In this study, the authors tested the hypothesis that behavioral response across social and nonsocial, novel and familiar conditions may be guided by the same trait(s) related to impulsivity in adult male rhesus macaques. The authors assessed 23 individuals' behavioral response to a series of nonsocial novel scenarios, as well as aggression and sociality within familiar and novel social contexts. Factor analysis of responses to nonsocial novelty identified two factors: Caution, which reflected latency to engage different novel situations, and Interest in Novelty, which consisted of duration and quality of exploration.

Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques.

The moderating effect of early experience on gene-behavior associations has been well characterized. The molecular events that allow for such moderation are not well understood, however. We assessed the impact of early experience and serotonin transporter linked promoter polymorphism (rh5-HTTLPR) genotype on peripheral serotonin transporter (5-HTT) regulation in response to a maternal/social separation and relocation stressor in infant rhesus macaques.

Serotonin function is associated with behavioral response to a novel conspecific in marmosets.

The function of the central nervous system neurotransmitter serotonin (5-HT) contributes to individual differences in impulsive behavior in humans and nonhuman primates. We investigated the relationship between 5-HT function and behavioral responses to a novel social scenario in marmosets. In the first study, marmosets (n=10) were treated orally with fluoxetine HCl (FLX) or vehicle for two trial periods and exposed to a novel conspecific for a 20-min trial following each treatment.

Molecular cloning of rat alpha1,3-fucosyltransferase IX (Fuc-TIX) and comparison of the expression of Fuc-TIV and Fuc-TIX genes during rat postnatal cerebellum development.

Fucosylated glycoconjugates play an essential role in central nervous system development, but the regulation of expression of these molecules is not well understood. The final biosynthetic step for a major group of cerebellar fucosylated glycoconjugates (those bearing the developmentally regulated epitope 3-fucosyl-N-acetyllactosamine, CD15, and related fucosylated epitopes) is catalyzed by an alpha-1,3-fucosyltransferase (FucT). The major FucT activity in postnatal rat cerebellum has a specificity consistent with that encoded by either a Fuc-TIV- or Fuc-TIX-like gene, and thus the expression of these genes was investigated during postnatal rat cerebellar development.