Oct. 26, 2004 SAN DIEGO -- Scientists at the OHSU Oregon National Primate Research Center and the University of Pittsburgh report significant stress early in life can have varying lifelong impacts depending on the timing of the stress exposure. The research also demonstrates that the impact can become even more profound when coupled with stress in adulthood. In a related but separate study, the researchers also observed the importance of timing in initiating therapies meant to counteract the impacts of early-life stress. The research is being presented this week at the 2004 Society for Neuroscience meeting in San Diego. Both studies were supported by the John D. and Catherine T. MacArthur Foundation Network on Early Experience and Brain Development and the National Institute of Mental Health.
"Past research conducted in both humans and animals has already established that significant stresses experienced early in life can cause problems in the development of social skills and behavioral problems that can last throughout childhood and into adulthood," said Judy Cameron, Ph.D., a scientist in the divisions of Reproductive Sciences and Neuroscience at the OHSU Oregon National Primate Research Center and a professor in the Department of Psychiatry at the University of Pittsburgh. "These problems can manifest themselves in a number of ways, including increased anxiety, anti-social behavior, depression, drug and alcohol abuse, and suicide. However, to this date, little information has been obtained as to whether the timing of early-life stress exposure can be linked to differing outcomes. In addition, few studies have been conducted to determine the best methods for preventing or counteracting the lifelong impacts of such early-life stress exposure."
Earlier studies have revealed that the first several months of life represent a dramatic period for brain development, especially in the neocortical regions of the brain, which are important in developing social skills. The development of neurons in this region takes place at an extremely accelerated rate during the first few months of life. In addition, important changes in brain chemistry are taking place during this period. Rapid changes in brain structure and function make the person or animal more susceptible to environmental impacts at these times in development.
Both studies being presented in San Diego were conducted using nonhuman primates. Past research has shown that monkeys are excellent models for studying the impacts of early childhood stress. Infant monkey behavioral changes caused by stress are very similar to those witnessed in human infants. In addition, studies using monkeys allow researchers to control factors such as the timing and duration of stress exposure, something not possible in human studies. Scientists also have a greater ability to observe the test subjects. In addition, nonhuman primate studies allow researchers to eliminate uncontrolled environmental factors that can skew the results of human studies.
To conduct the first study, researchers tracked a total of 15 animals. To simulate significant early-life stress in humans, the infant monkeys, who were living in social groups, experienced removal of their mother at varying times in infancy. The social groups included males and females of varying ages, much like groups naturally formed in the wild. In addition, all monkeys in the study were provided with toys and formula at the time of mother removal.
The monkeys were studied in three categories. The first category of infants was separated from their mothers during the first week of life, prior to the development of social skills. The second category of infants was separated from their mothers when they were 1 month of age, the stage when social skills are developing. The third category of infants had their mother removed from the social group at 6 months. This third category was considered a control group as monkeys in the wild become more independent from their mothers at approximately 6 months of age.
"We then studied the development of these three categories of monkeys and noticed differences in behavior related to the timing of separation," explained Cameron. "Monkeys separated at one week were less social when they were young, a characteristic that continues on into adulthood. The monkeys tended to exhibit a higher than normal amount of self-comforting behaviors, such as thumb or toe sucking. In addition, these monkeys tended to have less social dominance in the group setting, perhaps in relation to their reduced social skills. In contrast, monkeys separated at one month displayed increased seeking of social comfort and an increase in social dominance. In adulthood, these same monkeys spent more time involved in social play when compared to animals in the other groups. They also tended to be more dominant than other monkeys."
Researchers also tracked the responses of these three groups of animals in adulthood when they were placed with new social groups. The one-week separated animals seemed to be the most agitated by this social change. They tried many new behaviors, increased social behavior to the level of other groups of monkeys, increased in social dominance, but also threatened other monkeys more often. The one-month separated animals showed changes in eating behaviors and decreased play when placed in new social groups. In summary, the response to stress in adulthood was strongly influenced by whether and when animals had experienced stress in early life.
One important note is that earlier research suggests that stress sensitivity is heightened in individuals that undergo stresses early in life. This research shows that is not always the case and is at least partially dependent on the timing of the early-life stress.. The second, separate study that was conducted by the same research team extended the understanding of early life stress impacts. The study revealed the important role that timing plays in preventing behavioral problems associated with exposure to significant stresses during early childhood.
To simulate significant early-life stress in humans, the scientists separated nine infant monkeys from their mothers during the first week of life and placed them in social groups of three to four other monkeys. The social groups consisted of males and females ranging in ages, similar to groups formed in the wild. The researchers then introduced experienced mothers, often referred to as "super moms," when the infant monkeys were 1 to 3 months of age. These adoptive mothers were paired with the infant monkeys as a form of corrective therapy. The timing of the introduction of these "super moms" was varied because the scientists wanted to determine the optimal timing for initiation of therapies to counteract the impacts of the early-life stress.
"After being paired with the 'super moms,' we then observed the baby monkeys throughout their first year of life," explained Cameron. "As a control group for comparison, we observed the behavior of monkeys that lived with their natural mothers as well as a social group for the first six months of life. At six months the control monkeys had their mothers removed from the social group. Six months is the typical age when juvenile monkeys begin to gain independence from their mothers in the wild."
The scientists noted that the infants separated from their mothers at 1 week of age displayed a series of atypical behaviors. Specifically, these animals spent significantly more time alone than animals in the control group and limited their social contact. They also developed self-comforting behaviors, such as thumb or toe sucking. However, when separated monkeys were paired with an adoptive mother within the first month, all of these behaviors were rapidly reversed. For monkeys paired with adoptive mothers in the second month of life, the reversal took place, but at a slower pace. Monkeys paired in the third month of life did not exhibit a reversal of these atypical behaviors.
The researchers believe this study shows a small but distinct window of opportunity for possibly reversing or preventing poor social skill development due to early-life stress exposure.
"What this work appears to be telling us is that children separated from their mothers at birth should be placed in nurturing stable care situation as soon as possible to reduce the chances of developing socioemotional problems," explained Cameron. "This differs dramatically from the real-life policies in place in most states where a child is cared for, but not paired with a permanent family -- a period that can last months -- until a final decision is made as to whether they can be returned to their birth family."
"These findings underscore three core scientific principles that guide effective early childhood policy and practice," said Jack P. Shonkoff, M.D., dean of The Heller School for Social Policy and Management at Brandeis University and chair of the National Scientific Council on the Developing Child. "Early relationships are key to healthy development. Disrupted relationships have both immediate and long-term consequences. Relationship-based interventions can get kids back on track, but the clock is always ticking and the earlier the intervention the better the outcome."
The University of Pittsburgh School of Medicine is consistently ranked among the nation's leading medical schools. It is one of the university's six Schools of the Health Sciences, which include the schools of Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. Their combined mission is to train tomorrow's health care specialists and biomedical scientists, engage in groundbreaking research that will advance the understanding of the causes and treatments of disease, and to participate in the delivery of care as a partner with the University of Pittsburgh Medical Center. Among the many areas for which its faculty and programs are internationally recognized are oncology, psychiatry, genetics, transplantation and public health.
OHSU includes the schools of dentistry, medicine, nursing and science and engineering; OHSU Hospital and Doernbecher Children's Hospital; numerous primary care and specialty clinics; multiple research institutes; and several outreach and community service units.
The ONPRC is a registered research institution, inspected regularly by the United States Department of Agriculture. It operates in compliance with the Animal Welfare Act and has an assurance of regulatory compliance on file with the National Institutes of Health. The ONPRC also participates in the voluntary accreditation program overseen by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).
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