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When Early Life Stress Occurs Determines Its Impact Later, Timing Of Therapy To Counteract Effect Also Important

SAN DIEGO, October 24, 2004 Significant stress early in life can have varying lifelong impacts depending on the timing of the stress exposure, according to a report from scientists at the University of Pittsburgh, Oregon Health & Science University (OHSU) Oregon National Primate Research Center and Emory University. The impact can become even more profound when coupled with stress in adulthood, the research also demonstrates.

In a related but separate study, University of Pittsburgh and OHSU researchers found the impact of early life stress is counteracted if therapies are initiated at specific times during development. Both studies were presented today at the Annual Meeting of the Society for Neuroscience in San Diego.

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. This research shows that is not always the case and is at least partially dependent on the timing of the early life stress, said Judy Cameron, Ph.D., associate professor of psychiatry at the University of Pittsburgh School of Medicine and a scientist in the divisions of Reproductive Sciences and Neuroscience at the OHSU Oregon National Primate Research Center.

In humans, behavioral problems can manifest themselves in a number of ways including increased anxiety, antisocial behavior, depression, drug and alcohol abuse and suicide. However, to 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.

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 and rapid changes in brain structure and function make the person or animal more susceptible to environmental impacts.

Both studies presented in San Diego were conducted using non-human 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, non-human primate studies allow researchers to eliminate uncontrolled environmental factors that can skew the results of human studies.

To conduct the first study, researchers tracked 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. The monkeys were provided with toys and formula at the time of mother removal.

The monkeys were studied as three groups. The first group of infants was separated from their mothers during the first week of life, prior to the development of social skills. The second group was separated from their mothers when they were one month of age, when social skills are developing. Since monkeys in the wild become more independent from their mothers at approximately six months of age, this third group was considered a control group.

We then studied the development of these three categories of monkeys and noticed differences in behavior related to the timing of separation, explained Dr. Cameron. Monkeys separated at one week were less social when they were young, a characteristic that continued 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 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 and showed the greatest increase in agitated and aggressive behaviors. 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.

The second, separate study, conducted by the same research team, extended the understanding of the impact of early life stress. 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 of ranging ages, similar to groups formed in the wild. When the infant monkeys were one to three months of age, the researchers introduced experienced mothers, often referred to as super moms. 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 Dr. Cameron. As a control group for comparison, we observed the behavior of monkeys that lived with their natural mothers for the first six months of life. At six months the control monkeys were separated from their mothers and placed in social groups. 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 one 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 research 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 situations as soon as possible to reduce the chances of developing socioemotional problems, explained Dr. 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.

Both studies were supported by the John D. and Catherine T. MacArthur Foundation Network on Early Experience and Brain Development.

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