John P Capitanio

University of California, Davis | UCD · Department of Psychology

This is an obituary for Dr. Sally P. Mendoza.

Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of social impairment in low-social monkeys and children with autism, suggesting that AVP administration may improve primate social functioning. However, AVP administration also increases aggression, at least in “neurotypical” animals with intact AVP signaling. Here, we...

Comparative studies reliant on single personality surveys to rate wild primates are scarce yet remain critical for developing a holistic comparative understanding of personality. Differences in survey design, item exclusion, and factor selection impede cross-study comparisons. To address these challenges, we used consistently collected data to asse...

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys...

Background Type 2 Diabetes Mellitus (T2D) is a chronic disease with a high prevalence worldwide. Human literature suggests factors beyond well‐known risk factors (e.g., age, body mass index) for T2D: cytomegalovirus serostatus, season of birth, maternal age, birth weight, and depression. Nothing is known, however, about whether these variables are...

Background Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trai...

Individual differences of infant temperament have been associated with future health outcomes that provide explanatory power beyond adult personality. Despite the importance of such a metric, our developmental understanding of personality‐like traits is poor. Therefore, we examined whether young primates show consistency in personality traits throu...

Cortisol expression has been demonstrated to have variation across development in rhesus macaques ( Macaca mulatta ). There exists contradictory evidence for the nature of this change, and age at which it occurs, across biological sample types. Consequently, we lack a cohesive understanding for cortisol concentrations across the development of a ma...

Background Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance—in particular, parent of origin effects—may be involved. The ideal strategy for ascertaining parent of ori...

La personnalité est une construction complexe qui joue un rôle important dans la formation du comportement et des fonctions cognitives d'un individu. Elle est le fruit de l'interaction entre la génétique et l'environnement, et peut évoluer tout au long de la vie. Les facteurs sociaux, en particulier, sont un aspect important de l'effet environnemen...

Background Maternal obesity has been associated with a higher risk of pregnancy-related complications in mothers and offspring; however, effective interventions have not yet been developed. We tested two interventions, calorie restriction and pravastatin administration, during pregnancy in a rhesus macaque model with the hypothesis that these inter...

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 stu...

The neutrophil-to-lymphocyte ratio (NLR) is a predictor of morbidity for a variety of medical conditions, but little is known about how variation in NLR arises. We examined variation in this measure in a sample of 4577 infant rhesus monkeys (54.8% female), who participated in the BioBehavioral Assessment program at the California National Primate R...

Animal well-being can be assessed in a variety of ways; in this chapter, we focus on physiological measures of welfare and review advantages and disadvantages of measures assessing hypothalamic–pituitary–adrenal, sympathetic–adrenal–medullary, cardiovascular, and immune function. For each physiological system, measurement issues are discussed. Thro...

Rhesus monkeys and humans are highly social primates, yet both species exhibit pronounced variation in social functioning, spanning a spectrum of sociality. Naturally occurring low sociality in rhesus monkeys may be a promising construct by which to model social impairments relevant to human autism spectrum disorder (ASD), particularly if low socia...

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived...

Maternal gestational obesity is associated with elevated risks for neurodevelopmental disorder, including autism spectrum disorder. However, the mechanisms by which maternal adiposity influences fetal developmental programming remain to be elucidated. We aimed to understand the impact of maternal obesity on the metabolism of both pregnant mothers a...

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys...

We conducted a dose–response study of dexamethasone to investigate an optimal dexamethasone suppression test for common marmosets. Twelve marmosets received 0.1, 0.5, or 1.0 mg/kg dexamethasone. Doses of 0.5 and 1.0 mg/kg both suppressed endogenous cortisol for at least 18 h with greater individual variability in the lower 0.5 mg/kg dose.

As wildfires across the world increase in number, size, and intensity, exposure to wildfire smoke (WFS) is a growing health problem. To date, however, little is known for any species on what might be the behavioral or physiological consequences of prenatal exposure to WFS. Here we show that infant rhesus monkeys exposed to WFS in the first third of...

Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as “biological.” Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3‐ to 4‐month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their...

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. Specifically, in o...

Introduction Wildfire smoke (WFS) exposure is a growing threat to human health, and lower socioeconomic position (SEP) has been shown to increase pollution susceptibility. Studies of SEP-related susceptibility, however, are often compromised due to spatial confounding between lower-SEP and pollution. Here we examine outdoor-housed nonhuman primates...

Objective: Early life interindividual variation in hypothalamic-pituitary-adrenal (HPA) reactivity to stress is predictive of later life psychological and physical well-being, including the development of many pathological syndromes that are often sex-biased. A complex and interactive set of environmental and genetic causes for such variation has...

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived...

Animals vary on intrinsic characteristics such as temperament and stress responsiveness, and this information can be useful to experimentalists for identifying more homogeneous subsets of animals that show consistency in risk for a particular research outcome. Such information can also be useful for balancing experimental groups, ensuring animals w...

Previous reports suggest that female macaques with greater similarity in emotionality and nervous temperament, as evaluated in a well-established BioBehavioral Assessment (BBA) at the California National Primate Research Center, were more likely to form successful pairs. We tested whether the same measures can also predict the quality of social int...

Significance “Shelter in place” (SIP) orders have been deployed to slow the spread of SARS-CoV-2, but they induce social isolation that may paradoxically weaken antiviral immunity. We examined the impact of 2-wk SIP on immune cell population dynamics and gene regulation in 21 adult rhesus macaques, finding 30 to 50% declines in circulating immune c...

Background Rhesus monkeys ( Macaca mulatta ) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. T...

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 m...

Behavioral inhibition is a temperamental disposition to react warily when confronted by unfamiliar people, objects, or events. Behaviorally inhibited children are at greater risk of developing anxiety disorders later in life. Previous studies reported that individuals with a history of childhood behavioral inhibition exhibit abnormal activity in th...

People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low‐social monkeys show an increased burden of medical morbidities compared to their high‐social counterparts....

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 prenat...

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 cor...

Most primate species are highly social. Yet, within species, pronounced individual differences in social functioning are evident. In humans, the Social Responsiveness Scale (SRS) measures variation in social functioning. The SRS provides a quantitative measure of social functioning in natural social settings and can be used as a screening tool for...

A high-quality rhesus macaque genome Genome technology has improved substantially since the first full organismal genomes were generated. Applying new technology, Warren et al. refined the genome of the rhesus macaque, a model nonhuman primate. Long-read technology and other recent advances in sequencing technology were applied to generate a genome...

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. Specifically, in o...

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...

Naturally, low‐social rhesus macaques exhibit social impairments with direct relevance to autism spectrum disorder (ASD). To more efficiently identify low‐social individuals in a large colony, we exploited, refined, and psychometrically assessed the macaque Social Responsiveness Scale (mSRS), an instrument previously derived from the human ASD scre...

Mutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accura...

A geropathology grading platform (GGP) for assessing age-related lesions has been established and validated for in inbred strain of mice. Because nonhuman primates (NHPs) share significant similarities in aging and spontaneous chronic diseases with humans, they provide excellent translational value for correlating histopathology with biological and...

The Brazelton Neonatal Behavioral Assessment Scale (NBAS) evaluates a newborn infant's autonomic, motor, state, temperament, and social-attentional systems, which can help to identify infants at risk of developmental problems. Given the prevalence of rhesus monkeys being used as an animal model for human development, here we aimed to validate a sta...

Aspects of personality in nonhuman primates have been linked to health, social relationships, and life history outcomes. In humans as well as nonhuman primates, facial morphology is associated with assertiveness, aggression, and measures of dominance status. In this study we aimed to examine the relationship among facial morphology, age, sex, domin...

Background: Ozone (O3) inhalation elicits airway inflammation and impairs treatment responsiveness in asthmatic patients. The underlying immune mechanisms have been difficult to study because of the lack of relevant experimental models. Rhesus macaques spontaneously have asthma and have a similar immune system to human subjects. Objectives: We s...

Loneliness, or perceived social isolation, may be evident in any group-living species, although its assessment in nonhumans provides some measurement challenges. It is well-known that loneliness in humans confers significant risk for morbidity and mortality, although mechanisms remain unclear. The authors describe a naturally-occurring model of lon...

Mutation is the ultimate source of all genetic novelty and the cause of heritable genetic disorders. Mutational burden has been linked to complex disease, including neurodevelopmental disorders such as schizophrenia and autism. The rate of mutation is a fundamental genomic parameter and direct estimates of this parameter have been enabled by accura...

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 tw...

Ketamine is an N‐methyl‐D‐aspartate (NMDA) receptor antagonist widely used in pediatric anesthetic and therapeutic practices and veterinary medicine. Previous evidence suggests that exposure to ketamine during sensitive periods of development results in neural apoptosis and atypical behavior. Since monoamine neurotransmitters play important roles i...

This chapter examines personality in nonhuman primates where personality is seen as a dynamic, whole-organism phenomenon. Whereas in humans, the concept of personality is applied to persisting differences between individuals, in the world of animal biology, it is a concept that also describes species differences in adaptation to the environment, as...

Sexual dimorphism in body size, aggression, and dispersal patterns may affect the degree to which males and females perceive aggression from either sex as stressful. Whereas male macaques typically disperse to new groups at maturity, thus encountering many unfamiliar individuals of both sexes, females are philopatric, usually only encountering unfa...

Social instability in primate groups has been used as a model to understand how social stress affects human populations. While it is well established that individual cercopithecines have different temperaments or personalities, little is known about how temperament mediates the experience of social instability in large, naturalistic groups. Here, w...

Hair cortisol concentrations are increasingly being used in both humans and nonhuman animals as a biomarker of chronic stress. However, many details regarding how hair cortisol concentrations relate to the dynamic activity and regulation of the HPA axis are still unknown. The current study explores 1) how the regulation of the HPA axis in infancy r...

Behavioral inhibition (BI) refers to a pattern of timidity and avoidance in the face of novel people, objects, or situations. It was a concept originally identified in humans, but there is no a priori reason to assume that it is specific to our species. Here, we examine some of the conceptual and methodological issues associated with studying behav...

Prenatal androgen exposure (PAE) plays a pivotal role in masculinizing the developing body and brain, and extreme exposure may contribute to autism, anxiety disorder and schizophrenia. One commonly used biomarker for PAE is the pointer-to-ring-finger digit length (2D:4D) ratio. Although this biomarker is widely used in human studies, relatively few...

Previous research has repeatedly shown both personality and psychological stress to predict gastrointestinal disorders and chronic diarrhea in humans. The goal of the present research was to evaluate the role of personality, as well as psychological stressors (i.e., housing relocations and rearing environment), in predicting chronic diarrhea in cap...

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‐r...

Growing evidence identifies maternal adiposity as a potentially modifiable risk factor for adverse neurodevelopment. This retrospective cohort analysis examined whether maternal prepregnancy adiposity and gestational weight gain were associated with behavioral outcomes in 173 rhesus macaque infants at the California National Primate Research Center...

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhe...

The ability to recognize individuals is a critical skill acquired early in life for group living species. In primates, individual recognition occurs predominantly through face discrimination. Despite the essential adaptive value of this ability, robust individual differences in conspecific face recognition exist, yet its associated biology remains...

Human research into psychological processes such as anxiety, depression, or loneliness typically involves accruing cases in which the phenomenon of interest is naturally occurring, and then comparing such a sample with control cases. In contrast, animal research designed to model similar processes to test mechanistic hypotheses typically involves i...

While it is now well known that social deprivation during early development permanently perturbs affective responding, accumulating evidence suggests that less severe restriction of the early social environment may also have deleterious effects. In the present report, we evaluate the affective responding of rhesus macaque (Macaca mulatta) infants r...

Personality refers to differences between individuals in their usual patterns of behavioral and psychological interaction with the world. Personality research with nonhuman primates has focused on a number of topics: characterizing species differences in, and the evolution of, personality; understanding the development of personality, and brain mec...

Previous research has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type 1 interferon anti-viral genes in circulating blood cells. However, the impact of social conditions on lymphoid tissue gene regulation r...

Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus...

Face Recognition Memory Test and Response to Conspecific Social Signals Test raw data and analyses. (DOCX)

Face Recognition Memory Test Stimuli. (PDF)

Previous work has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type 1 interferon anti-viral genes in circulating blood cells. This project sought to determine whether social instability in rhesus macaques (N...

Background Although a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and...

Dataset.

Observed serum levels of Interleukin-6 (IL-6) relati