August 21, 2007

Child and Teen Brains Very Sensitive to Stress, Likely a Key Factor in Mental Illness

New research is showing that the brains of children and adolescent (teens) are much more sensitive to stress than the brains of adults. Chronic stress (or frequent periods of moderate stress) seems to be particularly damaging to these young brains. Researchers now believe that stress (as perceived by the individual) is likely to be an important risk factor in the development of schizophrenia and other mental illnesses and therefore stress is an important target to minimize or prevent mental illness.

Ongoing or frequent stress is now known to damage the brain's hypothalamus as well as the pituitary and adrenal glands in the brain (an area of the brain called the HPA axis because of the high level of interactions between these three brain areas). Together these brain areas control reactions to stress and regulate a number of important body processes including digestion, the immune system, mood, growth, body temperature and sexuality. The HPA-axis is also known to be a key area involved in schizophrenia and mood disorders.

This new research highlights the fact that neuroscience and psychology are now generally understood by researchers to be highly interdependent, and even different views of the same thing. In fact researchers, as can be seen below, increasingly have both neuroscience degrees and psychology degrees to integrate these two viewpoints.

Researchers are finding that chronic moderate stress or shorter term high stress can be much more harmful to the brain of young children and teens than it is to adults. Research we've reported on in the past has also shown that stress during pregnancy and early childhood can further increase the sensitivity of a child's brain to stress - thereby multiplying the risk of future mental illness.


Research has shown that when an adult animal is under chronic stress, stress hormones called glucocorticoids can attack nerve cells in the hippocampus, causing dendrites to shrivel and cells to shrink. Stress can also halt neurogenesis (growth of new brain cells). High levels of stress during childhood have been shown to be even more damaging; causing major neurological damage and endocrine disruption - including shutting down the growth hormone in the child and even slowing the rate that calcium is deposited in bone - with the result that the child does not grow as tall, and has much higher risk of osteoporosis compared to if he or she was in a less stressful environment. In the most severe cases of stress, children can stop growing all together.

In the amygdala, the brain's emotional center, the opposite occurs: More dendrites are grown from the neurons when an mammal is chronically stressed. Scientists now believe these changes may help to explain the behavior a person shows months after a highly stressful event such as surviving an assault, or in the death of a family member, or long term stressors such as persistent social stress, disruptive family stress and ongoing discrimination or bullying. Researchers have also strongly demonstrated that parent's can have a significant impact in the levels of stress a child experiences (both positive and negative) by way of different parenting approaches.

Shrinkage of brain cells in the hippocampus is associated with depression and memory loss. The growth of cells in the amygdala has been linked to overwhelming emotions, and in turn, anxiety disorders.

These changes in the hippocampus are usually reversible. Once the stress is removed or eliminated, memory and mood improve. But even in adults, changes in the amygdala - emotional changes - don't always change back.

Depression, what Dr. Robert Sapolsky of Stanford University has called the "common cold of psychopathology," attacks the hippocampus with stress hormones. Massive long-term depression, he said, was almost certain to cause permanent damage in the form of memory loss.

"All of this is perfectly disturbing, especially when you think about it in the realm of kids’ brains that are all about making new neurons and growing new processes. Everything I just told you about adult stress on the brain. . .multiply it ten-fold when you think about a ten year-olds brain."

In fact research studies have shown that children who grow up in households with high hostility levels between parents tend to have chronically elevated levels of stress hormones, frequently have very poor memory of their childhoods, and are predisposed to mental illness later in life.

Other research is suggesting that it is psychological or social stress that for children these days, is perhaps the most common type of stress. At the same time, high stress jobs have been shown to increase risk for depression and anxiety. This, and related research, suggests that these stress hormones likely plays a significant roll in mental illness in general, and schizophrenia specifically.

The Scientist magazine states that

"Elaine Walker, a developmental psychologist and neuroscientist at Emory University, says Russell Romeo's research (see below) is important in the context of psychological problems that emerge during adolescence. Stress is linked to virtually all physical and mental disorders, she says, adding that steroid hormones are believed to have both activational and organizational effects on the human brain. Walker also says that adolescence is a uniquely important time for intervention: "Preventive intervention in adolescence may be most effective because it is a developmental stage when we can most easily identify those who are vulnerable and potentially change the course of development." (Source: The Scientist magazine)

Russell Romeo, PHD, a researcher at Rockefeller University, is doing a lot of research in this area and it was the topic of a recent article in The Scientist magazine (a leading British science publication). We also interviewed Dr. Romeo by email to get a deeper look at his research as it relates to schizophrenia.

Russell Romeo (who has his PHD in neuroscience and psychology) is a young scientist at Rockefeller University who is trying to figure out how stress impacts the brains of adolescents. He is doing this by studying how stress impacts rats. Rats are commonly used in brain research because they share over 99% of the genes that humans have, and a long history of research suggests that their brains work very, very similarly to the way human brains work - so they are an inexpensive and ethical way to test the effects of stress on young mammals; a type of research that could not be done directly on humans due to ethical concerns. Because of these reasons, most experimental brain research today is done with rats.

Russell Romeo has found that juveniles were exposed to stress hormones longer (after a stressful event, or chronic stress) than the adults. "All things being equal, they're going to be experiencing higher levels [of stress hormones] for a longer period of time," and "This might be why stress can be so damaging to an individual during adolescence” he told The Scientist magazine.

Professor McEwen, a Professor at Rockefeller University, further stated that "the basic idea that has come from the kind of studies that I and Robert Sapolsky and others have done on animal models, is that the human brain does change volumetrically and functionally in some of these stress-related disorders" Professor McEwen and Russell Romeo’s research has demonstrated that chronic stress is reshaping the adolescent brain in sometimes permanent, sometimes harmful ways that are reflected directly in the brain cells.

These cellular modifications in the brain come at a particularly vulnerable time for teenagers. Most people who develop schizophrenia begin showing symptoms when they are in their teens. The occurrence of depression, which affects about two percent of children, impacts approximately seven percent of children after puberty. Although it is believed that genetic factors play a significant role in the risk of developing these diseases, some scientists say that chronic stress (or frequent stress) during adolescence tips the balance, causing someone who would otherwise be mentally sound to develop have a mental illness. Because of these factors, Russell Romeo believed that the impact of stress on the adolescent brain was an area that needed (and still needs) much more research.

About 4 years ago Russell Romeo began a new line of research that would transform the trajectory of his career. Romeo, then only 31 years old, was working in one of the best stress research labs in the country – Rockefeller University. Romeo was specifically interested in the transformation that takes place in human brains during the teen years. As is common in research labs worldwide today – Romeo began his studies using rats, because past research suggests that rats would provide a good example of what likely happens in human teen brains in response to stress.

At this time, not much was yet known about stress and how it impacts the adolescent brain. Romeo wondered if stress impacted young brains and older brains differently, in ways that other scientists and medical professionals had not noticed?

Romeo knew of two other experiments completed in the previous 20 years that had involved stressing adolescent rats. Romeo would expose his teenage rats to a different kind of stress: restraint. Restraint stress, he says, is both a physical and a psychological stressor, and he knew that it would activate the part of the brain that is called the hypothalamic-pituitary-adrenal (HPA) axis, the part of the brain hormone system that regulates stress.

Research has shown that if an animal encounters an experience that is stressful, the HPA axis is immediately activated -- and this is also true with humans. During the exposure to stress, the cells in the part of the brain known as the hypothalamus releases a hormone called corticotropin-releasing hormone (CRH). CRH then causes the pituitary, a small pea-sized gland situated near the base of the brain, to release another hormone called adrenocorticotropic hormone (ACTH). It is this hormone ACTH which causes the the adrenal glands to release glucocorticoids: cortisol in humans and corticosterone in rats.

Romeo's research focus was to first compare the stress response of young rats with that of adult rats to find out whether their stress response changed during puberty. In his experiment, Romero placed each rat under stress for a short time, and then measured the levels of stress hormones - corticosterone and ACTH - in its blood. After the experiment, Romeo measured the hormone levels in the blood samples.

The results of this first study were clear. In all the animals the stress hormone (corticosterone) levels had increased to approximately 420 nanograms directly after exposure to the stress. Thirty minutes later, however, the adult levels had decreased to about 150 ng, while the younger rat’s cortis levels remained suspended at 400 ng. By 60 minutes, adult cortisone levels were at 120 ng, while levels for the young rats had dropped to only 260 ng. 120 minutes later the adult cortisone had returned to their normal resting level, while for the young rats cortisone levels were still at about 80 ng, far above their normal resting level. While the young and old rats had both released similar amounts of corticosterone, the young rats took nearly an hour longer than the adults to recover from the stress.

The results was intriguing. The younger rats were experiencing a much longer response from the stress, which meant that the younger brain was exposed to stress hormones for a longer period of time than the adult brain.

While the implications of the extended response were not know to Romeo at the time, Romeo did know that puberty is a time of increased risk of drug abuse and mental disorders, and since these disorders appear to be provoked or made worse by stress, this area seemed ripe for additional research.

After getting approval from leaders in his lab, Romeo started another experiment. In this second experiment he wanted to find out the difference in stress response between young and mature rats exposed to chronic stress. This was an important thing to find out because researchers already had linked chronic stress to depression and other mental disorders in adults. By learning how chronic stress impacted the adolescent brain Romeo hoped to begin understanding how best to treat depression and other mental illnesses in younger people.

In this new study Romeo took 36 younger, and 36 older rats, and exposed them to chronic stress for 30 minutes each day for seven days. The key questions he was asking were how do the young rats and adults compare in their reactions to long-term stress? Does their response to the stress over time change?

For the adult rats the hormone levels increased dramatically on the first day of restraint, and then dropped each following day of exposure. It seemed that they were getting used to the stress and it didn’t bother them as much. In the young rats, the stress hormone levels increased dramatically (higher than the adult’s response) on the first day, and continued to increase on subsequent days, and did not decrease as long as the young rat was exposed to the stress. However, as soon as the stress was eliminated (the rat no longer restrained) the young rats returned to their normally low levels of stress much faster.

Romeo also learned that chronic stress during the rat’s teen years also led to changes in their behavior – they lost weight, had higher levels of corticosterone and displayed the symptoms of depression that is typical in learned helplessness.

In contrast, the adults did not show these behavioral changes. These research results, Romeo suggests, suggest that mammals are very sensitive to stress during their teen / adolescent period of life. Additional research is needed to find out why this is the case.

Romeo said that in his new research he will focus on other brain neurotransmitters – especially norepinephrine and serotonin. He would like to learn how exactly adolescent stress impacts these brain chemicals.

Romeo told The Scientist magazine that "We know that dysfunction of these pathways in adulthood can lead to psychological disorders, but know relatively little how challenges during puberty may affect their immediate or long-term functioning,"

Romeo said that researchers do know that stress, which is generally linked to depression and anxiety disorders, impacts the young brain very differently than the adults’ brain. He believes that therefore treatments should reflect this fact - and suggests that treating younger adults and children the same as adults is likely a problem.

Dr. Romeo also mentioned the recent progress in "modeling" schizophrenia in mice, such as described in the paper cited below just appeared in the journal of Molecular Psychiatry this week.

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia, Mol Psychiatry. 2007 Aug;12(8):756-66. Epub 2007 Apr 24.

Russell Romeo believes it would be interesting to start studying these mice and their responses to stress, especially during perinatal development. However, at this time, he is not sure what has and hasn't been done with mouse models such as these. We'll report more as the progress continues in this important area.

Related Reading:

The Long-term Impact of Stress During Childhood on Brain Development

Stress and Pregnancy

How to Prevent Schizophrenia, Reduce Risk of Mental Illness

Stress and the Brain - Long Term Impact

The Devastating Effects Of Stress On Children

Stress and the Cellular Response to Dopamine

Recommended Book:

Why Zebras Don't Get Ulcers: An Updated Guide To Stress, Stress Related Diseases, and Coping

Scientific Presentation (PDF): Adolescence and Stress: Negative Outcomes in Adult Function and Mental Health

Three Key Scientific Papers by Russell Romeo

R.D. Romeo et al., "Testosterone cannot activate an adult-like stress response in prepubertal male rats," Neuroendocrinol, 79:125-32, 2004.

R.D. Romeo et al., "Stress history and pubertal development interact to shape hypothalamic pituitary adrenal axis plasticity," Endocrinol, 147:1664-74, 2006.

R.D. Romeo, B.S. McEwen, "Stress and the adolescent brain," Ann NY Acad Sci, 1094:202-14, 2006.


Has anyone had any experience with Tianeptine (Stablon)? If you have, could you please post your experience with it. I'm looking to see how others feel on this drug.

Posted by: Cory Schulz at August 22, 2007 10:03 AM

this is a really interesting topic

Posted by: susan at September 26, 2007 11:21 AM

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