David Baxter PhD
Late Founder
Children and Teen Brains Very Sensitive to Stress, Likely a Key Factor in Mental Illness
August 21, 2007
New research is showing that the brains of children and adolescent (teens) are much more sensitive to stress than the brains of adults. Researchers believe that this is likely to be an important factor in the development of schizophrenia and other mental illnesses that begin during the teen years, and therefore stress is a potential target to minimize or prevent mental illness.
At a high level, 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 it is chronic moderate stress or shorter term high stress that is the most damaging to the brain. Additionally, past research has also shown that stress during pregnancy can further increase the sensitivity of a child's brain to stress - thereby increasing 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). In the amygdala, the brain's emotional center, the opposite occurs: More dendrites are grown from the neurons when an animal is chronically stressed.
Scientists 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 and ongoing discrimination. 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 relieved, memory and mood improve. But in adults, changes in the amygdala - emotional changes - don't always change back.
Depression, what Dr. Robert Sapolsky of Stanford University has termed the "common cold of psychopathology," also 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.
Other research is suggesting that it is psychological or social stress that for children these days, is perhaps the most common type of stress. High stress jobs have been shown to increase risk for depression and anxiety. This, and related research, suggests that these stress hormones may play a key roll in serious mental illness in general, and schizophrenia specifically.
The Scientist magazine states that
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 by doing research with 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.
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 for a longer period of time," and "This might be why stress can be so damaging to an individual during adolescence."
"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," McEwen says. Chronic stress is reshaping the brain in sometimes permanent, sometimes harmful ways. The amygdala, the hippocampus, and the prefrontal cortex are three brain areas that undergo major changes during puberty.
These cellular changes come at a particularly vulnerable time for teenagers. The overwhelming majority of people with schizophrenia start showing symptoms as adolescents. The prevalence of depression, which affects about two percent of children, climbs to seven percent after puberty. Although genetic factors play a large role in the onset of these diseases, some scientists say that chronic stress during adolescence tips the balance, causing someone who would otherwise be mentally sound to have a mental disorder. For all of these reasons, Romeo believed that the effects of stress on the changing brain during adolescence was an area that needed more research.
4 years ago, Russell Romeo started an experiment that would change the course of his career. Romeo, only 31 years old at the time, was a young neuroscientist working in one of the best stress research labs in the country, he was fascinated by recent research on the vast remodeling that takes place in the human brain during adolescence. Rats, Romeo felt, would provide a good model for better understanding the adolescent stress response in humans.
Very little was known about stress and the adolescent brain. Was it possible that stress affected young brains and older brains differently, in ways that researchers and clinicians had overlooked?
His question was simple: Do adolescents and adults undergo a similar brain hormone response when stressed? He knew of two other experiments in the previous 20 years that had involved stressing adolescent rats by using foot shock or ether inhalation. Romeo was subjecting 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.
When an animal encounters a stressful experience, the HPA axis is immediately activated. Cells in the hypothalamus release corticotropin-releasing hormone (CRH), which triggers the pituitary, a pea-sized gland nestled into a bony enclave at the base of the brain, to secrete adrenocorticotropic hormone. ACTH then acts on the adrenal glands to release glucocorticoids: cortisol in humans and corticosterone in rats.
Romeo's plan was to first compare the stress response of young rats with that of adult rats to find out whether stress reactivity changed during puberty. In his experiment, he would put each rat under stress for a short time, and then measure the levels of stress hormones - corticosterone and ACTH - in its blood. After the experiment, Romeo measured the hormone levels in the blood samples.
When he arrived at the lab the morning after his experiment and started to check the levels of the stress hormones in the rats' blood, he remembers the raw data of the hormone levels coming off the printer. To maintain the integrity of the experiment, the data was blinded, so he didn't know which number was associated with which rat. Romeo began matching number to animal and punching them into a computer spreadsheet. "I'm going, holy s***,' as I'm putting them in," he says. "I'm looking at the data and thinking, wow, this really is a robust effect'."
In all the animals, the corticosterone levels had shot up to about 420 nanograms immediately followed the stressor. After 30 minutes, however, adult levels had dropped down to about 150 ng, while the juveniles' 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. Two hours later, adult cortisone had returned to basal level, while the juveniles' cortisone levels were still at about 80 ng, far above base level. Both released similar amounts of corticosterone, but the young rats took nearly an hour longer than the adults to recover. ACTH levels were showing a similar pattern.
The juvenile animal was mounting a longer stress response, which meant that the juvenile brain was exposed to stress hormones for a longer period than the adult brain. Romeo thought the physiologic and behavioral implications of the extended response were unknown, but since puberty is a time of increased susceptibility to drug abuse and mental disorders, and since these disorders appear to be exacerbated by stress, this area of research, he concluded, needed further investigation.
With the lab's senior advisor's blessing, Romeo initiated a second experiment. In his first, he had examined the hormonal stress response between adults and juveniles by looking at an acute, one-time stressor and found that hormonally, juveniles take longer to recover. In the second, he wanted to test the difference between the pups and the adult rats under chronic stress. This was an important step, because scientists knew that chronic stress was linked to depression and other mental disorders in adults. Knowing how chronic stress affected the adolescent brain could potentially shed light onto treatment for these disorders.
This time, Romeo stressed the rats - 36 young and 36 old - for thirty minutes each day for seven days. His questions: How do young rats and adults compare in their reactions to long-term stress? If they've experienced the stressor before, will they react to it differently when it repeats?
In the adult rats, hormone levels shot up on the first day of restraint but then dropped each ensuing day, as if they were growing accustomed to the stress. In the juveniles, on the other hand, corticosterone levels shot up even higher after the first day of stress and didn't drop until the stressor was removed. But, once it was removed, the juveniles showed a much faster return to baseline.
Chronic stress during adolescence, Romeo found, also led to changes in the behavior of his rats. When he subjected rats to stress throughout the course of puberty, they lost weight, had elevated levels of corticosterone, and showed symptoms of depression, like learned helplessness. This was not the case for adults subjected to stress. These data, he says, indicate that animals are particularly sensitive to stress during adolescence, but it will take more investigation to determine exactly what is changing during puberty to account for the difference in stress reactivity.
Romeo's next line of research, however, will be to investigate neurotransmitter systems, with a particular focus on norepinephrine and serotonin. He will investigate how adolescent stress affects the serotonergic and noradrenergic pathways in the brain. "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 wrote in a recent e-mail.
What Romeo does know is that stress, often linked to depressive and anxiety disorders, affects the adolescent human brain differently than that of an adult. And, he says that treatment should vary accordingly. The lumping together of age groups is a problem, he says. "Psychological dysfunction in adolescence is a very different beast from psychological dysfunction in adults, just like it's very different when you have psychological dysfunction in an aged person versus a young adult." In other words, he says, adults and teenagers may require different drugs and different treatment plans. He says he hopes that his research will help advance treatment designed specifically for teenagers.
Romeo found that for adolescent rats, stress was also linked to signs of depression. By stressing adolescent rats and then observing them in an open maze and a forced swim test, Romeo has found that they are particularly sensitive to stressors, more sensitive than adults. The adolescent rats that were isolated or restrained in Romeo's experiments lost more weight, struggled less in the swim test and showed less movement in the open maze. Rats that he restrained as adolescents were also more prone to showing depressive tendencies later in life.
Dr. Romeo also mentioned to us that there has been some progress in "modeling" schizophrenia in mice, such as described in the paper cited below just appeared in the journal 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.
Related Reading:
Stress and Pregnancy
Stress and the Brain - Long Term Impact
The Devastating Effects Of Stress On Children
Scientific Presentation:
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.
August 21, 2007
New research is showing that the brains of children and adolescent (teens) are much more sensitive to stress than the brains of adults. Researchers believe that this is likely to be an important factor in the development of schizophrenia and other mental illnesses that begin during the teen years, and therefore stress is a potential target to minimize or prevent mental illness.
At a high level, 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 it is chronic moderate stress or shorter term high stress that is the most damaging to the brain. Additionally, past research has also shown that stress during pregnancy can further increase the sensitivity of a child's brain to stress - thereby increasing 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). In the amygdala, the brain's emotional center, the opposite occurs: More dendrites are grown from the neurons when an animal is chronically stressed.
Scientists 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 and ongoing discrimination. 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 relieved, memory and mood improve. But in adults, changes in the amygdala - emotional changes - don't always change back.
Depression, what Dr. Robert Sapolsky of Stanford University has termed the "common cold of psychopathology," also 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 stuff 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 children who grow up in argumentative households tend to have chronically elevated levels of stress hormones, and frequently have very poor memory of their childhoods 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. High stress jobs have been shown to increase risk for depression and anxiety. This, and related research, suggests that these stress hormones may play a key roll in serious 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."
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 UK 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 by doing research with 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.
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 for a longer period of time," and "This might be why stress can be so damaging to an individual during adolescence."
"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," McEwen says. Chronic stress is reshaping the brain in sometimes permanent, sometimes harmful ways. The amygdala, the hippocampus, and the prefrontal cortex are three brain areas that undergo major changes during puberty.
These cellular changes come at a particularly vulnerable time for teenagers. The overwhelming majority of people with schizophrenia start showing symptoms as adolescents. The prevalence of depression, which affects about two percent of children, climbs to seven percent after puberty. Although genetic factors play a large role in the onset of these diseases, some scientists say that chronic stress during adolescence tips the balance, causing someone who would otherwise be mentally sound to have a mental disorder. For all of these reasons, Romeo believed that the effects of stress on the changing brain during adolescence was an area that needed more research.
4 years ago, Russell Romeo started an experiment that would change the course of his career. Romeo, only 31 years old at the time, was a young neuroscientist working in one of the best stress research labs in the country, he was fascinated by recent research on the vast remodeling that takes place in the human brain during adolescence. Rats, Romeo felt, would provide a good model for better understanding the adolescent stress response in humans.
Very little was known about stress and the adolescent brain. Was it possible that stress affected young brains and older brains differently, in ways that researchers and clinicians had overlooked?
His question was simple: Do adolescents and adults undergo a similar brain hormone response when stressed? He knew of two other experiments in the previous 20 years that had involved stressing adolescent rats by using foot shock or ether inhalation. Romeo was subjecting 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.
When an animal encounters a stressful experience, the HPA axis is immediately activated. Cells in the hypothalamus release corticotropin-releasing hormone (CRH), which triggers the pituitary, a pea-sized gland nestled into a bony enclave at the base of the brain, to secrete adrenocorticotropic hormone. ACTH then acts on the adrenal glands to release glucocorticoids: cortisol in humans and corticosterone in rats.
Romeo's plan was to first compare the stress response of young rats with that of adult rats to find out whether stress reactivity changed during puberty. In his experiment, he would put each rat under stress for a short time, and then measure the levels of stress hormones - corticosterone and ACTH - in its blood. After the experiment, Romeo measured the hormone levels in the blood samples.
When he arrived at the lab the morning after his experiment and started to check the levels of the stress hormones in the rats' blood, he remembers the raw data of the hormone levels coming off the printer. To maintain the integrity of the experiment, the data was blinded, so he didn't know which number was associated with which rat. Romeo began matching number to animal and punching them into a computer spreadsheet. "I'm going, holy s***,' as I'm putting them in," he says. "I'm looking at the data and thinking, wow, this really is a robust effect'."
In all the animals, the corticosterone levels had shot up to about 420 nanograms immediately followed the stressor. After 30 minutes, however, adult levels had dropped down to about 150 ng, while the juveniles' 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. Two hours later, adult cortisone had returned to basal level, while the juveniles' cortisone levels were still at about 80 ng, far above base level. Both released similar amounts of corticosterone, but the young rats took nearly an hour longer than the adults to recover. ACTH levels were showing a similar pattern.
The juvenile animal was mounting a longer stress response, which meant that the juvenile brain was exposed to stress hormones for a longer period than the adult brain. Romeo thought the physiologic and behavioral implications of the extended response were unknown, but since puberty is a time of increased susceptibility to drug abuse and mental disorders, and since these disorders appear to be exacerbated by stress, this area of research, he concluded, needed further investigation.
With the lab's senior advisor's blessing, Romeo initiated a second experiment. In his first, he had examined the hormonal stress response between adults and juveniles by looking at an acute, one-time stressor and found that hormonally, juveniles take longer to recover. In the second, he wanted to test the difference between the pups and the adult rats under chronic stress. This was an important step, because scientists knew that chronic stress was linked to depression and other mental disorders in adults. Knowing how chronic stress affected the adolescent brain could potentially shed light onto treatment for these disorders.
This time, Romeo stressed the rats - 36 young and 36 old - for thirty minutes each day for seven days. His questions: How do young rats and adults compare in their reactions to long-term stress? If they've experienced the stressor before, will they react to it differently when it repeats?
In the adult rats, hormone levels shot up on the first day of restraint but then dropped each ensuing day, as if they were growing accustomed to the stress. In the juveniles, on the other hand, corticosterone levels shot up even higher after the first day of stress and didn't drop until the stressor was removed. But, once it was removed, the juveniles showed a much faster return to baseline.
Chronic stress during adolescence, Romeo found, also led to changes in the behavior of his rats. When he subjected rats to stress throughout the course of puberty, they lost weight, had elevated levels of corticosterone, and showed symptoms of depression, like learned helplessness. This was not the case for adults subjected to stress. These data, he says, indicate that animals are particularly sensitive to stress during adolescence, but it will take more investigation to determine exactly what is changing during puberty to account for the difference in stress reactivity.
Romeo's next line of research, however, will be to investigate neurotransmitter systems, with a particular focus on norepinephrine and serotonin. He will investigate how adolescent stress affects the serotonergic and noradrenergic pathways in the brain. "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 wrote in a recent e-mail.
What Romeo does know is that stress, often linked to depressive and anxiety disorders, affects the adolescent human brain differently than that of an adult. And, he says that treatment should vary accordingly. The lumping together of age groups is a problem, he says. "Psychological dysfunction in adolescence is a very different beast from psychological dysfunction in adults, just like it's very different when you have psychological dysfunction in an aged person versus a young adult." In other words, he says, adults and teenagers may require different drugs and different treatment plans. He says he hopes that his research will help advance treatment designed specifically for teenagers.
Romeo found that for adolescent rats, stress was also linked to signs of depression. By stressing adolescent rats and then observing them in an open maze and a forced swim test, Romeo has found that they are particularly sensitive to stressors, more sensitive than adults. The adolescent rats that were isolated or restrained in Romeo's experiments lost more weight, struggled less in the swim test and showed less movement in the open maze. Rats that he restrained as adolescents were also more prone to showing depressive tendencies later in life.
Dr. Romeo also mentioned to us that there has been some progress in "modeling" schizophrenia in mice, such as described in the paper cited below just appeared in the journal 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.
Related Reading:
Stress and Pregnancy
Stress and the Brain - Long Term Impact
The Devastating Effects Of Stress On Children
Scientific Presentation:
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.
