Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains.

Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior.

Background: In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today.

Objectives: The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model.

Four decades of leading-edge research in the reproductive and developmental sciences: the Infant Primate Research Laboratory at the University of Washington National Primate Research Center.

The Infant Primate Research Laboratory (IPRL) was established in 1970 at the University of Washington as a visionary project of Dr. Gene (Jim) P. Sackett.

Post-drug consequences of chronic atypical antipsychotic drug administration on the ability to adjust behavior based on feedback in young monkeys.

Rationale: Atypical antipsychotic drugs are characterized by their affinity for serotonin and dopamine receptors. The dopaminergic system undergoes developmental changes during childhood, making it vulnerable to external influences such as drug administration.

Objective: The purpose of this study was to assess the long-term effects of administering risperidone and quetiapine to 12-24-month-old macaque monkeys on cognitive development, a maturational equivalent to 4-8-year-old children.

Comparability of developmental cognitive assessments between standard and computer testing methods.

Substantial questions have been raised about the validity of using computer-based testing to assess cognitive development with young children. However, little work has been done to assess the comparability of performance elicited using computerized methods with performance garnered using standard testing methods. The purpose of this study was to establish whether computerized testing resulted in performance that was different than established performance norms for infant monkeys (Macaca nemestrina) tested on four highly used cognitive tasks.

A computer touch screen system and training procedure for use with primate infants: Results from pigtail monkeys (Macaca nemestrina).

Computerized cognitive and perceptual testing has resulted in many advances towards understanding adult brain-behavior relations across a variety of abilities and species. However, there has been little migration of this technology to the assessment of very young primate subjects. We describe a training procedure and software that was developed to teach infant monkeys to interact with a touch screen computer.

The effect of experience on the development of tactual-visual transfer in pigtailed macaque monkeys.

The study described here is the first to experimentally demonstrate the effects of experience on the development of tactual-visual transfer. Infant pigtailed macaque monkeys (Macaca nemestrina) were reared from birth to 2 months of age in special cages that allowed the separation of tactual and visual experience. When assessed on a battery of measures at the end of the 2-month period, animals reared without the opportunity to integrate information across the two sensory modalities performed at chance levels on a paired-comparison measure of tactual-visual transfer and performed worse than controls in a visually guided reaching task.

Beta-endorphin levels in longtailed and pigtailed macaques vary by abnormal behavior rating and sex.

Frequent or severe abnormal behavior may be associated with the release of endorphins that positively reinforce the behavior with an opiate euphoria or analgesia. One line of research exploring this association involves the superhormone, proopiomelanocortin (POMC). The products of POMC appear to be dysregulated in some human subjects who exhibit self-injurious behavior (SIB).

Trisomy 16 in a pigtailed macaque (M. nemestrina) with multiple anomalies and developmental delays.

A female pigtailed macaque (Macaca nemestrina) with unusual physical characteristics, deficits in learning and cognitive tasks, abnormal social behavior, and abnormal reflexes and motor control was followed from birth until 3 years of age and found to have trisomy 16, which is homologous to trisomy 13 in humans. The animal described here showed similar features to cases of trisomy 16 and 18 (human trisomy 13 and 18, respectively) reported previously in nonhuman primates. However, both significant differences and similarities were found when compared with the homologous human trisomy.

Survival, growth, health, and reproduction following nursery rearing compared with mother rearing in pigtailed monkeys (Macaca nemestrina).

Nursery-reared primates do not experience psychological "maternal bonding" or immunological benefits of breast milk, so they are expected to be inferior to mother-raised monkeys in growth, health, survival, reproduction, and maternal abilities. Studies of nursery-reared monkeys support aspects of this prediction for infants deprived of social contact or raised in pairs. We present colony record data on 1,187 mother and 506 nursery-raised monkeys, 2-10 yr of age, living in mixed groups.

Characteristics of early rhythmic behaviors in children at risk for developmental disorders.

Objective: Abnormal stereotyped behaviors are a significant problem for many individuals with mental retardation or mental illness. To increase understanding of the development of abnormal stereotyped behaviors, the authors investigated the early rhythmic behaviors of children at increased risk for developmental delays.

Method: Rhythmic behaviors in 13-month-old children born prematurely and in children born at term were coded from laboratory videotapes of structured interaction segments.

Behavioral responses of longtailed macaques to different cage sizes and common laboratory experiences.

The authors tested the effects of varying cage size on the behavior of 10 female and 10 male Macaca fascicularis by singly caging them for 2 weeks in each of 5 cage sizes, ranging from approximately 20% to 148% of regulation size. Behavior in the regulation cage size, a size 23% smaller, and a size 48% larger did not differ in any analysis. Locomotion was significantly less in the 2 smallest cage sizes.

Sex differences in compatibility of pair-housed adult longtailed macaques.

This research was designed to evaluate the effects of same-sex pair housing on the psychological well-being of adult wild-born longtailed macaques (Macaca fascicularis). We studied behavioral compatibility and stress as measured by urinary cortisol excretion in 15 pairs of each sex. Before they were housed together, the pairs were categorized by noncontact pairedpreference testing as preferred, nonpreferred, or randomly assigned partners.

Urinary cortisol responses of longtailed macaques to five cage sizes, tethering, sedation, and room change.

Urinary free cortisol responses to five cage sizes, cage level, room change, tethering adaptation, chronic catheterization, and ketamine sedation were measured in 14 female and 14 male wild-born adult Macaca fascicularis. Urinary free cortisol, a physiological measure of psychological well-being that can be collected unobtrusively, provided a measure of the animals' general adrenocortical response to various conditions over a time course of hours. Urinary free cortisol values in response to stimulation with adrenocorticotropic hormone (ACTH) validated the measure as a reflection of blood values.

Growth of nursery-raised Macaca nemestrina infants: Effects of feeding schedules, sex, and birth weight.

Ponderal growth, caloric intake, growth velocity, and growth efficiency were studied from birth through 90 days in 523 nursery-raised pigtailed macaque infants. The male and female subjects ranged in birth weight from the 1st through 100th centiles of the colony distribution and were all judged to be clinically healthy. One group of infants was fed on an ad lib schedule, with formula continuously available from dispensers which were replenished every 8 h.

Rearing infant monkeys (Macaca nemestrina) in pairs produces deficient social development compared with rearing in single cages.

Many scientists and colony managers assume that social housing is a beneficial living condition for all captive primates. Several older studies of primate development question the generality of this assumption. We recently tested this assumption by comparing the social development of pigtailed macaque infants raised in pairs and those that were raised in individual cages.

Sires influence fetal death in pigtailed macaques (Macaca nemestrina).

Computerized colony records were used to identify dams and sires whose reproductive histories while breeding in harem groups indicated high or low risk for producing fetal deaths. The monkeys were then singly caged and bred within and between risk conditions during 24- to 72-hour matings. Although the low- and high-risk sires did not differ in ability to achieve conceptions, the results revealed that reproductive history predicted subsequent fetal death rates, and sires made a substantial contribution.

Effects of management methods, social organization, and physical space on primate behavior and health.

The incidence of clinical treatment in a large colony of pigtailed macaques (Macaca, nemestrina) was studied retrospectively to assess the effectiveness of three sequential housing and management protocols. In the initial standard protocol, groups were housed in single rooms, with each room occupied by a different group after daily cleaning. In the experimental protocol, animals were housed in two-room suites dedicated exclusively to the resident group.

Measurement of excreted steroids in Macaca nemestrina.

A practical method for the quantitative measurement of the estrogenic steroid estradiol-17β in the feces of pigtailed macaques (Macaca nemestrina) is described. The method, which includes homogenization, filtration, ether extraction, and sephadex purification, produces an 85.3% recovery of 3H-estradiol.

Perinatal hypothermia and maternal temperature declines during labor in pigtailed macaques (Macaca nemestrina).

Body temperature, respiration, and heart rate were recorded for 90 perinatal pigtailed macaques (Macaca nemestrina) within the first hour after birth. Hypothermia and corresponding depressed respiration and heart rate were evident in all animals. Regression analysis revealed that time-since-birth accounted for most of the observed variance in all measures.

Maintenance of high-density lipoprotein blood levels prior to spontaneous abortion in pig-tailed macaques (Macaca nemestrina).

Blood was drawn throughout the first half of the pregnancies of 24 pig-tailed macaques (Macaca nemestrina) to evaluate longitudinal high-density lipoprotein (HDL) changes. In all 15 normal pregnancies, HDL decreased at least 50%; the mean value for the group fell from 0.45 gm/liter to 0.

Parturition in Macaca nemestrina.

Measures were taken on 187 pregnancies of 104 pig-tailed macaques (Macaca nemestrina) to document the normative course of parturition and to identify factors correlated with high risk for poor pregnancy outcomes. Analyses involved weekly physical examinations and diurnal sleep-wake-fulness patterns during trimester three; behavior during labor and delivery; and newborn sex, Apgar ratings, birthweight, and reflexes. Onset of labor was estimated at three-four hours before delivery, the time when circadian activity level first deviated from its predelivery pattern.