| Stress and the Developing Brain |
Het
onderstaande artikel is in het Engels en afkomstig van het National
Institute of Mental Health. Het artikel is ook verkrijgbaar in PDF formaat.
Stress and the Developing Brain (3 pages, 117KB)
Stress and the Developing Brain
It is well known that the early months and years of life are critical for brain
development. But the question remains: just how do early influences act on the brain
to promote or challenge the developmental process? Research has suggested that many
both positive and negative experiences, chronic stressors, and various other environmental
factors may affect a young child's developing brain. And now, studies involving
animals are revealing in greater detail how this may occur.
One important line of research has focused on brain systems that control stress
hormones—cortisol, for example.1,2 Cortisol and other stress hormones
play an important role in emergencies: they help our bodies make energy available
to enable effective responses, temporarily suppress the immune response, and sharpen
attention. However, a number of studies conducted in people with depression indicate
that excess cortisol released over a long time span may have many negative consequences
for health.3,4,5 Excess cortisol may cause shrinking of the hippocampus,
a brain structure required for the formation of certain types of memory.
In
experiments with animals, scientists have shown that a well-defined period of early
postnatal development may be an important determinant of the capacity to handle
stress throughout life.2 In one set of studies, rat pups were removed
each day from their mothers for a period as brief as 15 minutes and then returned.
The natural maternal response of intensively licking and grooming the returned pup
was shown to alter the brain chemistry of the pup in a positive way, making the
animal less reactive to stressful stimuli. While these pups are able to mount an
appropriate stress response in the face of threat, their response does not become
excessive or inappropriate. Rat mothers who spontaneously lick and groom their pups
with the same intensity even without human handling of the pups also produce pups
that have a similarly stable reaction, including an appropriate stress hormone response.6
Striking differences were seen in rat pups removed from their mothers for periods
of 3 hours a day, a model of neglect compared to pups that were not separated. After
3 hours, the mother rats tended to ignore the pups, at least initially, upon their
return. In sharp contrast to those pups that were greeted attentively by their mothers
after a short absence, the "neglected" pups were shown to have a more profound and
excessive stress response in subsequent tests. This response appeared to last into
adulthood.7,8
The implications of these animal studies are worrisome. However, research is in
progress to determine the extent to which the hypersensitive or dysregulated stress
response of "neglected" rat pups can be reversed if, for example, foster mothers
are provided who will groom the pups more intensely, or if the animals are raised
in an "enriched" environment following their separation. An enriched setting may
include, for example, a diverse and varied diet, a running wheel, mazes, and changes
of toys.
Animal investigators are well aware of another kind of long-term change, again rooted
in the first days of life. Laboratory rats are often raised in shoebox cages with
few sources of stimulation. Scientists have compared these animals to rats raised
in an enriched environment and found that the "privileged" rats consistently have
a thicker cerebral cortex and denser networks of nerve cells than the "deprived"
rats.9,10
Another study recently reported that infant monkeys raised by mothers who experienced
unpredictable conditions in obtaining food showed markedly high levels of corticotrophin
releasing factor (CRF) in their cerebrospinal fluid and, as adults, abnormally low
levels of cerebrospinal fluid cortisol.11 This is a pattern often seen
in humans with post-traumatic stress disorder and depression.
5 The distressed monkey mothers, uncertain about finding food, behaved
inconsistently and sometimes neglectfully toward their offspring. The affected young
monkeys were abnormally anxious when confronted with separations or new environments.
They were also less social and more subordinate as adult animals.
It is far too early to draw firm conclusions from these animal studies about the
extent to which early life experience produces a long-lived or permanent set point
for stress responses, or influences the development of the cerebral cortex in humans.
However, animal models that show the interactive effect of stress and brain development
deserve serious consideration and continued study.
References
- McEwen BS. Allostasis and allostatic load: implications
for neuropsychopharmacology. Neuropsychopharmacology, 2000;
22(2): 108-24.
- Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D,
Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ.
Maternal care, hippocampal glucocorticoid receptors, and
hypothalamic-pituitary-adrenal responses to stress. Science,
1997; 277(5332): 1659-62.
- Sheline YI, Sanghavi M, Mintun MA, Gado MH. Depression
duration but not age predicts hippocampal volume loss in
medically healthy women with recurrent major depression.
Journal of Neuroscience, 1999; 19(12): 5034-43.
- Brown ES, Rush AJ, McEwen BS. Hippocampal remodeling
and damage by corticosteroids: implications for mood disorders.
Neuropsychopharmacology, 1999; 21(4): 474-84.
- Heim C, Newport DJ, Heit S, Graham YP, Wilcox M, Bonsall
R, Miller AH, Nemeroff CB. Pituitary-adrenal and autonomic
responses to stress in women after sexual and physical abuse
in childhood. Journal of the American Medical Association,
2000; 284(5): 592-7.
- Francis D, Diorio J, Liu D, Meaney MJ. Nongenomic transmission
across generations of maternal behavior and stress responses
in the rat. Science, 1999; 286(5442): 1155-8.
- Plotsky PM, Meaney MJ. Early, postnatal experience alters
hypothalamic corticotropin-releasing factor (CRF) mRNA,
median eminence CRF content and stress-induced release in
adult rats. Brain Research. Molecular Brain Research, 1993;
18(3): 195-200.
- Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney
MJ, Plotsky PM. Long-term behavioral and neuroendocrine
adaptations to adverse early experience. Progress in Brain
Research, 2000; 122: 81-103.
- Jones TA, Klintsova AY, Kilman VL, Sirevaag AM, Greenough
WT. Induction of multiple synapses by experience in the
visual cortex of adult rats. Neurobiology of Learning and
Memory, 1997; 68(1): 13-20.
- Green EJ, Greenough WT, Schlumpf BE. Effects of complex
or isolated environments on cortical dendrites of middle-aged
rats. Brain Research, 1983; 264(2): 233-40.
- Coplan JD, Andrews MW, Rosenblum LA, Owens MJ, Friedman
S, Gorman JM, Nemeroff CB. Persistent elevations of cerebrospinal
fluid concentrations of corticotropin-releasing factor in
adult nonhuman primates exposed to early-life stressors:
implications for the pathophysiology of mood and anxiety
disorders. Proceedings of the National Academy of Sciences
USA, 1996; 93(4): 1619-23.
All material in this fact sheet is in the public domain and
may be copied or reproduced without permission from the Institute.
Citation of the source is appreciated.
NIH Publication No. 01-4603
National Institute of Mental Health (NIMH)
Office of Communications and Public Liaison
Public Inquiries: (301) 443-4513
Media Inquiries: (301) 443-4536
E-mail:
nimhinfo@nih.gov
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http://www.nimh.nih.gov
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