The Invisible Epidemic: Post-Traumatic Stress Disorder, Memory
and the Brain
J. Douglas Bremner, M.D.
http://www.thedoctorwillseeyounow.com/articles/behavior/ptsd_4/
Dr. Bremner
is a faculty member of the Departments of Diagnostic Radiology and Psychiatry,
Yale University School of Medicine, Yale Psychiatric Institute, and
The research reviewed in this article was supported by an NIH-sponsored
General Clinical Research Center (GCRC) Clinical Associate Physician (CAP)
Award and a VA Research Career Development Award to Dr. Bremner,
and the National Center for PTSD Grant.
Post-traumatic Stress Disorder (PTSD) is something of an
invisible epidemic. The events underlying it are often mysterious and always unpleasant.
It is certainly far more widespread than most people realize. For example, a
prime cause of PTSD is childhood sexual abuse. About 16% of American women
(about 40 million) are sexually abused (including rape, attempted rape, or
other form of molestation) before they reach their 18th birthday.1
Childhood abuse may be the most common cause of PTSD in
American women, 10% of whom suffer from PTSD (compared to 5% for men) at some
time in their lives,2
but many other types of psychological trauma can cause the disorder -- car
accidents, military combat, rape and assault. Symptoms of PTSD include
intrusive memories, nightmares, flashbacks, increased vigilance, social
impairment and problems with memory and concentration.
It's
Not Just Psychological
While such symptoms are commonly understood to be psychological problems, some
or all of them may well be related to the physical effects of extreme stress on
the brain.3,4
Recent studies have shown that victims of childhood abuse and combat veterans
actually experience physical changes to the hippocampus, a part of the brain
involved in learning and memory, as well as in the handling of stress.5
The hippocampus also works closely with the medial prefrontal cortex, an area
of the brain that regulates our emotional response to fear and stress. PTSD sufferers often have impairments in one or both of these
brain regions. Studies of children have found that these impairments can lead
to problems with learning and academic achievement.
Other typical symptoms of PTSD in children, including fragmentation of memory,
intrusive memories, flashbacks, dissociation (or the unconscious separation of
some mental processes from the others, e.g., a mismatch between facial
expression and thought or mood), and pathological ("sick") emotions,
may also be related to impairment of the hippocampus.6
Damage to the hippocampus, which processes memory, may explain why victims of
childhood abuse often seem to have incomplete or delayed recall of their
abusive experiences.7
A Disease of Memory
Memory problems play a large part in PTSD. PTSD patients report deficits in
declarative memory (remembering facts or lists -- see below), fragmentation of
memory and dissociative amnesia (gaps in memory
lasting from minutes to days that are not caused by ordinary forgetting).
Psychiatric
Symptoms Associated with Childhood Abuse
PTSD
Dissociative
Anxiety
Substance
Abuse
Many abuse victims report that they remember seemingly
random or minor details of the abuse event, while forgetting central events.
For instance, one woman who had been locked in a closet had an isolated memory
of the smell of old clothes and the sound of a clock ticking. Later, she
connected these details with feelings of intense fear; only then was she able
to recall the whole picture of what had happened to her. PTSD also causes
problems with non-declarative memory (subconscious or motor memory, such as
remembering how to ride a bicycle). This can show up as abnormal conditioned
responses and the reliving of traumatic experiences when something happens to
remind the sufferer of past abuse. These types of memory disturbance may also
be related to physical changes in the hippocampus and medial prefrontal cortex.
How
Psychological Trauma Affects the Hippocampus and Memory
Childhood abuse and other sources of extreme stress can have lasting effects on
the parts of the brain that are involved in memory and emotion. The
hippocampus, in particular, seems to be very sensitive to stress.8,9,10,11,12,13,14,15,16
Damage to the hippocampus from stress can not only cause problems in dealing
with memories and other effects of past stressful experiences, it can also
impair new learning.17,18
Exciting recent research has shown that the hippocampus has the capacity to
regenerate nerve cells ("neurons") as part of its normal functioning,
and that stress impairs that functioning by stopping or slowing down neuron
regeneration.19,20
We recently conducted a study to try to see if
PTSD symptoms matched up with a measurable loss of neurons in the hippocampus.
We first tested
Figure 1

Our study showed that diminished right hippocampal
volume in the PTSD patients was associated with short-term memory loss.22
Similar results were found when we looked at PTSD sufferers who were victims of
childhood physical or sexual abuse.23,24
More recent studies have since confirmed hippocampal
volume reduction in PTSD25,26
These studies also show that hippocampal volume
reduction is specific to PTSD and is not associated with disorders such as
anxiety or panic disorders.27
Further study on the question of memory and the hippocampus may some day
shed light on the controversy surrounding delayed recall, or so-called
"recovered memories" of childhood abuse. The hippocampus plays an
important role in connecting and organizing different aspects of a memory and
is thought to be responsible for locating the memory of an event in its proper
time, place and context.
We suspect that damage to the hippocampus following exposure to the stress
brought on by childhood abuse leads to distortion and fragmentation of
memories. For instance, in the case of the PTSD sufferer who was locked in a
closet as a child, she had a memory of the smell of old clothes but other parts
of her memory of the experience, such as a visual memory of being in the closet
or a memory of the feeling of fear, are difficult to retrieve or completely
lost. In cases like this, psychotherapy or an event that triggers similar
emotions may help the patient restore associations and bring all aspects of the
memory together.
This new understanding of the way childhood trauma affects memory and the brain
has important implications for public health policy. One example would be the
case of inner-city children who have witnessed violent crimes in their
neighborhoods and families. If this kind of stress can cause damage to brain
areas involved in learning and memory, it would put these children at a serious
academic disadvantage in ways and for reasons that programs such as Head Start
may be unable to address. Studies confirm this: in war-torn
PTSD and Other
Brain Areas
Besides the hippocampus, abnormalities of other brain areas, including medial
prefrontal cortex, are also associated with PTSD.
The medial prefrontal cortex regulates emotional and fear responses.29
The medial prefrontal cortex is closely linked to the hippocampus. In several
studies we have found dysfunction of both the medial prefrontal cortex and the
hippocampus at times when patients were suffering from PTSD symptoms.31
We believe that dysfunction in these medial prefrontal regions may underlie
pathological emotional responses in patients with PTSD.30
For example, we sometimes see a failure of extinction of fear responses -- a
rape victim who was raped in a dark alley will have fear reactions to dark
places for years after the original event, even though there is no threat
associated with a particular dark place. In a study using combat-related slides
and sounds to provoke PTSD symptoms, combat veterans with PTSD had decreased
blood flow in the area of the medial prefrontal cortex. Significantly, this did
not occur in combat veterans without PTSD32
We saw similar results when we compared women with
PTSD and a history of childhood sexual abuse to women with a history of abuse
but no PTSD.
Conclusion
Traumatic stress, such as that caused by childhood sexual abuse, can have
far-reaching effects on the brain and its functions. Recent studies indicate
that extreme stress can cause measurable physical changes in the hippocampus
and medial prefrontal cortex, two areas of the brain involved in memory and
emotional response. These changes can, in turn, lead not only to classic PTSD
symptoms, such as loss and distortion of memory of events surrounding the
abuse, but also to ongoing problems with learning and remembering new
information. These findings may help explain the controversial phenomenon of
"recovered" or delayed memories. They also suggest that how we
educate, rehabilitate and treat PTSD sufferers may need to be reconsidered.
|
March
2000 |
|
References
1. McCauley J,
2. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB (1995). Posttraumatic
stress disorder in the national comorbidity survey.
Arch Gen Psychiatry 52:1048-1060. return
3. Bremner JD, Marmar
C (eds.) (1998): Trauma, Memory and Dissociation, APA Press,
4. Saigh PA, Bremner
JD (Eds.) (1999). Posttraumatic Stress Disorder: A Comprehensive Text,
5. Bremner JD, Narayan
M (1998): The effects of stress on memory and the hippocampus throughout the
life cycle: Implications for childhood development and aging. Develop
Psychopath 10:871-886. return
6. Bremner JD, Southwick SM, Charney DS (1999): The
neurobiology of posttraumatic stress disorder: An integration of animal and
human research. In: Saigh, P., Bremner,
J.D. (Eds.): Posttraumatic Stress Disorder: A Comprehensive Text,
7. Bremner JD, Krystal
JH, Charney DS, Southwick SM (1996): Neural
mechanisms in dissociative amnesia for childhood abuse:
Relevance to the current controversy surrounding the "False Memory
Syndrome". Am J Psychiatry 153(7):FS71-82. return
8. McEwen BS, Angulo J, Cameron H, Chao HM, Daniels D, Gannon MN, Gould E, Mendelson
S, Sakai R, Spencer R, Woolley C (1992): Paradoxical
effects of adrenal steroids on the brain: Protection versus degeneration. Biol Psychiatry 31:177-199. return
9. Sapolsky RM (1996). Why stress is
bad for your brain. Science 273:749-750. return
10. Uno H, Tarara
R, Else JG, Suleman MA, Sapolsky RM (1989): Hippocampal
damage associated with prolonged and fatal stress in primates. J Neurosci 9:1705-1711. return
11. Sapolsky RM, Uno H, Rebert
CS, Finch CE (1990): Hippocampal damage associated
with prolonged glucocorticoid exposure in primates. J
Neurosci 10:2897-2902. return
12. Woolley CS, Gould E, McEwen BS: Exposure to excess glucocorticoids
alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 1990; 531:225-231. return
13. Virgin CE, Taryn
PTH, Packan DR, Tombaugh
GC, Yang SH, Horner HC, Sapolsky RM (1991). Glucocorticoids inhibit glucose transport and glutamate
uptake in hippocampal astrocytes:
implications for glucocorticoid neurotoxicity.
J Neurochem 57:1422-1428. return
14. McEwen BS, Conrad CD, Kuroda Y, Frankfurt M, Magarinos
AM, McKittrick C (1997). Prevention of stress-induced
morphological and cognitive consequences. Eur Neuropsychopharm
7:(suppl)3:S322-328. return
15. Smith MA, Makino S, Kvetnansky
R, Post RM (1995). Stress and glucocorticoids affect
the expression of brain-derived neurotrophic factor
and neurotrophin-3 mRNA in the hippocampus. J Neurosci
15:1768-1777. return
16. Nibuya M, Morinobu
S, Duman RS (1995). Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure
and antidepressant drug treatments. J Neurosci
15:7539-7547. return
17. Luine V, Villages M,
18. Bodnoff SR, Humphreys AG,
Lehman JC, Diamond DM, Rose GM, Meaney
MJ (1995): Enduring effects of chronic corticosterone
treatment on spatial learning, synaptic plasticity, and hippocampal
neuropathology in young and mid-aged rats. J Neurosci
15:61-69. return
19. Gould E, Tanapat P, McEwen BS, Flugge G, Fuchs E (1998) Proliferation of granule cell
precursors in the dentate gyrus of adult monkeys is
diminished by stress. PNAS 95:3168-3171. return
20. Sass KJ, Spencer DD, Kim JH, Westerveld
M, Novelly RA, Lencz T
(1990). Verbal memory impairment correlates with hippocampal
pyramidal cell density. Neurology 40:1694-1697. return
21. Bremner JD, Scott TM, Delaney RC,
Southwick SM, Mason JW, Johnson DR, Innis RB,
McCarthy G, Charney DS (1993): Deficits in short-term
memory in post-traumatic stress disorder. Am J
Psychiatry 150:1015-1019. return
22. Bremner JD, Randall PR, Scott
TM, Bronen RA, Delaney RC, Seibyl
JP, Southwick SM, McCarthy G, Charney DS, Innis RB (1995): MRI-based measurement of hippocampal volume in posttraumatic stress disorder. Am J Psychiatry 152:973-981. return
23. Bremner JD, Randall PR, Capelli
S, Scott T, McCarthy G, Charney DS (1995): Deficits
in short-term memory in adult survivors of childhood abuse. Psych Res 59:97-107. return
24. Bremner JD, Randall P, Vermetten E, Staib L, Bronen RA, Mazure CM, Capelli S,
McCarthy G, Innis RB, Charney DS (1997): MRI-based measurement of hippocampal volume in posttraumatic stress disorder related
to childhood physical and sexual abuse: A preliminary report. Biol Psychiatry 41:23-32. return
25. Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B (1997): Hippocampal volume in women victimized by childhood sexual
abuse. Psychol Medicine 27:951-959. return
26. Gurvits TG, Shenton
MR, Hokama H, Ohta H,
27. Bremner JD, Licinio
J, Darnell A, Krystal JH, Owens M, Southwick SM, Nemeroff CB, Charney DS (1997):
Elevated CSF corticotropin-releasing factor
concentrations in posttraumatic stress disorder. Am J
Psychiatry 154:624-629. return
28. Saigh PA, Mroweh
M, Bremner JD (1997) Scholastic impairments among
traumatized adolescents. Beh Res
Ther 35:429-436. return
29. Morgan MA, LeDoux JE (1995):
Differential contribution of dorsal and ventral medial prefrontal cortex to the
acquisition and extinction of conditioned fear in rats. Behav
Neurosci 109:681-688. return
30. Bremner JD, Krystal JH, Southwick SM, Charney DS (1995) Functional neuroanatomical
correlates of the effects of stress on memory. J Trauma Stress
8:527-554. return
31. Bremner JD, Innis
RB, Ng CK, Staib L, Duncan J, Bronen
R, Zubal G, Rich D, Krystal
JH, Dey H, Soufer R, Charney DS (1997): PET measurement of central metabolic
correlates of yohimbine administration in
posttraumatic stress disorder. Arch Gen Psychiatry 54:246-256. return
32. Bremner JD, Staib
L, Kaloupek D, Southwick SM, Soufer
R, Charney DS (1999): Positron emission tomographic (PET)-based measurement of cerebral blood flow
correlates of traumatic reminders in Vietnam combat veterans with and without
posttraumatic stress disorder. Biol Psychiatry (In press). return