Wounds That Time Won’t Heal:
The Neurobiology of Child Abuse
Martin H. Teicher
http://www.mclean.harvard.edu/about/bios/detail.php?username=mteicher
Neuropsychologist Teicher reveals the alarming
connections scientists are discovering between child abuse—even when it is
psychological, not
http://192.211.16.13/curricular/hhd2006/news/wounds.pdf
Neurobiological Correlates of Childhood Maltreatment
http://www.drugabuse.gov/MeetSum/stressabstracts.html
Martin
H. Teicher, M.D., Ph.D., Carl M. Anderson, Ph.D., Susan
L. Andersen, Ph.D., Ann Polcari, R.N., M.S.C.S.,
Ph.D.(c)
The focus
of this presentation will be on neurobiological and neuropsychiatric
abnormalities in individuals with a history of childhood abuse. These abnormalities will be compared with the reported
effects of early stress on brain development of rodents and primates. To a great degree, the neuropsychiatric
abnormalities observed in humans who have survived intense early stress
dovetail with results from controlled studies in mammals and nonhuman primates. These observations underscore the importance and relevance
of animal research to our efforts to delineate the genesis of mental disorders
and to devise therapeutic or preventive strategies.
Research
that we have conducted delineates a constellation of abnormalities that have
been associated with childhood abuse. There are three
major components to the constellation. One factor we
have labeled "limbic irritability." It is
manifested by markedly increased prevalence of symptoms suggestive of temporal
lobe epilepsy (TLE) and by an increased incidence of clinically significant EEG
abnormalities. The second component is deficient
development and differentiation of the left hemisphere. This
is manifest throughout the cerebral cortex and hippocampus. The
third component is deficient left-right hemispheric integration, which is
indicated by markedly lateralized shifts in hemispheric activity and by
attenuated development of the middle portions of the corpus callosum, which is
the primary pathway connecting the two hemispheres.
The
initial sequelae of abuse may be either a
constellation of internalizing symptoms, such as depression, anxiety, suicidal
ideation, and posttraumatic stress, or an externalizing cluster that includes
aggressive-impulsivity, delinquency, and substance abuse. Studies
have shown that abused children may show some degree of neurological
dysfunction even in the absence of apparent or reported head injury. Green et al. (1981) found that soft neurological signs and
nonspecific EEG abnormalities were more common in physically abused children
without known head trauma. Davies (1979) reported that
in a sample of 22 patients involved as the child or younger member of an
incestuous relationship, 77 percent had EEG abnormalities and 36 percent had
clinical seizures. However, neither Green et al.
(1981) nor Davies (1979) postulated that these abnormalities were a consequence
of the abuse. Rather, they perceived the
neurobiological abnormality as a preexisting vulnerability that increased risk
of being victimized.
We have
initiated a program of research endeavoring to test the hypothesis that early
childhood maltreatment acting as a severe stressor produces a cascade of
physiological and neurohumoral responses that lead to
enduring deleterious effects on brain development. This
is a difficult hypothesis to test in humans, as abuse is not necessarily a
random act. If we observe an association between a
history of abuse and presence of an abnormality, it may be the case that the
abuse caused the abnormality. It can also be argued
that the abnormality occurred first and increased the likelihood of abuse or
that the abnormality runs in families and leads to an increased frequency of
abusive behavior in family members or relatives. One
approach to this problem is to conduct analogous studies of severe early stress
in animals that are randomly assigned to treatments. The
observation of parallel outcomes bolsters the hypothesis that this is a cause
and effect relationship.
Association
Between Early Abuse and Ratings of Limbic Irritability
in Adulthood
To
explore the potential relationship between early abuse and limbic system
dysfunction, we devised the Limbic System Checklist-33 (LSCL-33; Teicher et al., 1993) to ascertain the frequency with which
patients experience symptoms often encountered as ictal
TLE phenomena (e.g., Spiers et al., 1985). These items consisted of paroxysmal somatic disturbances,
brief hallucinatory events, visual phenomena, automatism, and dissociative experiences. Psychometric
evaluation indicated that LSCL-33 scores had high test-retest reliability (r =
.92; n = 16). Scores were low in normal controls (<
10) and elevated in patients with documented TLE (> 23).
We
studied 253 adults presenting for outpatient psychiatric assessment (mean age,
34 yr; 58 percent female). The Life Experience
Questionnaire (LEQ; Bryer et al., 1987) was used to
ascertain abuse history. Subjects who reported no
abuse (n = 109) had mean LSCL-33 scores of 13.6 (±11.3). Total
LSCL-33 scores were 38 percent greater in patients with physical abuse, but not
sexual abuse (p < .01; n = 77) and were 49 percent greater in patients with
sexual abuse, but not physical abuse (p < .02; n = 26). Patients
who acknowledged both physical and sexual abuse (n = 41) had scores 113 percent
greater than patients denying abuse (p < .0001). LSCL-33
scores from both males and females were affected by abuse in the same manner.
Association
Between Early Abuse and EEG Abnormalities in Childhood
A chart
review was conducted to blindly examine the association between different types
of abuse and quantifiable abnormalities on imaging, EEG, and neuropsychological
testing (Ito et al., 1993). Medical records were
reviewed on 115 consecutive admissions to a child and adolescent psychiatric hospital. Four groups were established based on abuse ratings. Subjects in the nonabused group
had no evidence of abuse in any of the four categories (n = 27). Patients in the psychological abuse group had experienced
psychological abuse or neglect but had not been physically or sexually abused
(n = 22). Patients in the overall physical/sexual
abuse group had experienced probable or definite physical or sexual abuse (n =
55). Patients in the severe physical/sexual abuse
subgroup had a documented history of severe physical or sexual abuse (n = 38).
There
were no differences between abused and nonabused
patients in the prevalence of abnormal neurological exams. Abnormal
imaging studies were found in 15 percent of nonabused
patients and in 26 percent of abused patients. Abnormal
EEG studies were found in 26.9 percent of the nonabused
patients but in 54.4 percent of the patients with a history of early
maltreatment (p = .021). Abnormal EEG studies were
observed in 42.9 percent of the patients with psychological abuse or neglect,
59.6 percent of the total sample with physical/sexual abuse (p = .014), and
71.9 percent of the subsample with serious
physical/sexual abuse (p = .0013). Maltreated and
adequately treated patients differed most clearly in the prevalence of
left-sided frontotemporal abnormalities (p = .036). They did not differ in the prevalence of either
right-sided abnormalities (p > .8) or bilateral abnormalities (p > .5). Neuropsychological test results were reviewed for evidence
of right-left hemispheric asymmetries (i.e., substantially better
visual-spatial ability than verbal performance). Overall,
in the adequately treated group, left hemisphere deficits were 2.25-fold more
prevalent than right hemisphere deficits. In the total
maltreatment group, left-sided deficits were 6.67-fold more prevalent than
right, and left hemisphere deficits were 8-fold more prevalent than right-sided
deficits in patients with a history of neglect or psychological abuse. Thus, maltreatment appears to be associated with an increased
prevalence of left-sided EEG abnormalities and left-sided neuropsychological
deficits.
EEG
Coherence Measures of Brain Development
EEG
coherence is a parameter that indicates the degree of synchrony ("shared
activity" or interconnectivity) between two EEG leads across a portion of
the bandwidth. Coherence is affected by the adequacy
and degree of myelinization of long association
fibers and by the degree and complexity of local axodendritic
connections in the underlying cortex (Thatcher et al., 1987, 1992). Highly developed local cortical connections modify the EEG
signal under the lead and decrease coherence between leads. In
most instances, abnormally elevated levels of coherence are an indication of
inadequate cortical development or maturation. Further,
coherence decreases as EEG leads are moved farther apart. The
rate of decay of coherence over distance is a direct index of the complexity
and differentiation of local cortical connections (Thatcher et al., 1986). Hence, combined assessment of EEG coherence and coherence
decay provides an objective measure of cortical maturation and differentiation.
Fifteen
child or adolescent inpatients (10.7±2.5 yr, 7M:8F, 10 medicated) with a
history of intense physical or sexual abuse, confirmed by DSS, were recruited
(Ito et al., 1998). The controls were 15 healthy
volunteers. All subjects were between 6 and 15 years
of age, right handed with no history of neurological disorders or abnormal
intelligence. Diagnostic data were derived from
discharge diagnosis and structured clinical interviews.
To reduce
the number of possible statistical comparisons, we derived composite measures
of average left and average right hemisphere alpha EEG coherence based on all
possible lead pairings within each hemisphere. Abused
children had greater average left hemisphere coherence than normal children (p
= .007), but a comparable degree of right hemisphere coherence (p > .7). In controls, the laterality index was -3.21 percent. In contrast, abused children had an average laterality
index of +7.21 percent (p < .02), indicating significantly greater left vs.
right coherence. There was no specific relationship
between degree of asymmetry and diagnosis. The
asymmetry was apparent whether their primary diagnosis was depression, PTSD, or
conduct disorder. Abused subjects differed from
controls in degree of asymmetry in central (p = .02), temporal (p < .03),
and parietal regions (p < .055). Alpha EEG
coherence decayed markedly over distance, and the rate of decay was well fit (r
> .9) by a power function. In normal controls,
coherence decayed at a more rapid rate in the left vs. right hemisphere. In contrast, patients with a history of severe abuse had a
lower rate of decay in their left hemisphere than in their right hemisphere (p
< .05). Overall, normal controls had a 16.3 percent
greater rate of coherence decay in their left vs. right hemisphere, while
abused subjects had a 6.8 percent lower rate of coherence decay in their left
vs. right hemisphere (p < .04). Hence, these
findings suggest that childhood abuse is associated with deficient maturation
of the left hemisphere - both in relationship to normal controls and in
relationship to their own right hemisphere.
Right-Left
Evoked Response Asymmetry During Recall of Unpleasant
Early Memories in Psychologically Traumatized Subjects
Schiffer,
Teicher, and Papanicolau
(1995) used probe auditory evoked potential (AEP) attenuation as a measure of
hemispheric activity to study the effects of early trauma on cerebral
laterality. We sought to assess whether early
traumatic experience affected the degree of right-sided activation during
recall of painful memories. To evaluate this
hypothesis, hemispheric activity was measured in adult subjects under two
conditions: (1) during recall of a neutral memory and (2) during recall of an
unpleasant affectively laden early memory. Subjects
were exposed to repeated auditory clicks, during measurement of the amplitude
of the AEP. Theoretically, if one hemisphere is more
actively involved in a competing mental activity than the other hemisphere,
then AEPs recorded over the more distracted
hemisphere should be weaker (Papanicolau and Johnstone, 1984; Papanicolau et
al., 1983a,b).
Twelve unmedicated right-handed adults who had a history of
emotional abuse were recruited and compared with 12 similar nonabused
controls. AEPs were recorded
while subjects recalled a neutral memory and responses to an abbreviated POMS
scale were ascertained. A short empathic psychiatric
interview was conducted to evoke recall of a disturbing childhood memory. The AEPs were then repeated. The unpleasant memory always followed the neutral memory
task because of concern that unpleasant memories would interfere with the
neutral task. Averaged AEP recordings were blindly
read by an experienced researcher to obtain N1 and P2 peaks. Of
the 20 subjects with artifact-free AEPs, 10 subjects
(32.9 yr; M5/F5) had experienced significant childhood trauma and 10 had not
(33.0 yr; M4/F6). There was no significant difference
between the POMS scores of the two groups during the neutral memories. Both groups reported higher mean POMS scores following the
unpleasant memory, but the scores were slightly greater in patients with a
history of emotional abuse.
The
trauma group displayed significant left dominant asymmetry during the neutral
memory (asymmetry index = -15.9 percent; p < .02), and right dominance
during the unpleasant memory (asymmetry index = +12.2 percent; p < .10). Overall, trauma subjects had a highly significant
asymmetry shift between conditions (p = .007). In
contrast, the control group had no significant asymmetry or shift during either
state. ANCOVA was used to control for differences in
degree of emotional response (all combinations). Statistical
differences between groups in degree of asymmetry shift were not a consequence
of differences in magnitude of expressed emotional response.
Adult
patients with a history of significant early stress had more lateralized shifts
in cortical activity as a consequence of their affective state or nature of
recalled memory. While they were thinking about a
neutral memory, their left auditory cortex was more preoccupied and less
available to process the sounds. In contrast, the
right auditory cortex was more preoccupied and otherwise engaged when they were
thinking about a disturbing childhood memory. In
healthy controls, both hemispheres were equally involved in processing and
responding to neutral and disturbing memories. These
findings are consonant with observations of Rauch et al. (1996), who found,
using PET scans, that individuals with PTSD (including several with childhood
trauma) showed specific activation of their limbic system in the right but not
left hemisphere during exposure to traumatic reminders.
Association
between childhood abuse and regional anatomy of the corpus callosum in children. As our research suggested that
early abuse is associated with diminished left hemisphere cortical development
and decreased right-left cortical integration, we sought to ascertain whether
there were abnormalities in the regional anatomy of the corpus callosum in
children with a history of abuse or neglect. Medical
records were reviewed on 115 consecutive pediatric patients admitted to
An
automated algorithm was used to divide the corpus callosum into seven regions
as defined by Witelson et al. (1989). In order to control for differences in corpus callosum
size due to age or gender, regional volume was corrected for total brain volume. MRI measures were performed by independent researchers
blind to all clinical variables. In addition, MRI
images from 97 carefully screened healthy normal control children were obtained
from Dr. J. Giedd at the Child Psychiatry Branch of
the National Institute of Mental Health (NIMH). Mean age
was 11.5 ± 3.5 years, and 63 percent were male. Data
were analyzed separately for males and females, as previous research has shown
that early experience exerts sexually dimorphic effects on the development of
the corpus callosum (Denenberg et al., 1983).
Relative
regional corpus callosum size was assessed in hospitalized boys with history of
abuse or neglect, hospitalized boys without any history of abuse or neglect but
with serious psychiatric illness (contrast group), and normal healthy boys
studied at the NIMH. Overall, there were prominent
group differences in the rostral body and anterior
and posterior midbody of the corpus callosum (all p
< .006). Within these regions, there were no
significant differences between the contrast group and the health controls. However, in the abused group these regions (and also the
isthmus) were between 23 percent and 31 percent smaller than in the healthy
normal controls (all p < .004). Hence, abuse or
neglect, but not psychiatric illness, was associated with a marked and
significant reduction in the size of the middle portion of the corpus callosum.
Stepwise
regression analyses were performed to ascertain the factors most directly
associated with the changes in relative regional corpus callosum size. Results from this analysis indicate that neglect was
associated with a marked (24 - 42 percent) reduction in the relative size of
all regions of the corpus callosum. In contrast,
physical abuse was associated with a significant reduction only in the anterior
midbody, and sexual abuse was associated with a
reduction in the splenium. Hence,
this analysis suggests that neglect may produce particularly severe impact on
the relative regional size of the corpus callosum of boys.
Surprisingly,
stepwise multiple regression of the female population revealed a different
pattern or association. While neglect was consistently
associated with diminished corpus callosum size in boys, sexual abuse was a
more powerful factor in girls. Indeed, a history of
sexual abuse was associated with an 18 percent to 30 percent reduction in size
of the rostral body, anterior and posterior midbody, and isthmus. This again
points out that the middle portions of the corpus callosum may be most
vulnerable to the effects of early experience but that girls and boys may
differ in their windows of vulnerability. Neglect in
girls was associated with an increase in the size of region 6 and a decrease in
the size of region 7. This most likely reflects an
alteration in the shape of the corpus callosum with a bulging of the isthmus at
the expense of the splenium.
Sánchez
et al. (1998) found that differential rearing experience affected the
development of the corpus callosum and the cognitive function of male rhesus
monkeys. Briefly, infant monkeys raised individually
in a nursery from
Berrebi
et al. (1988) showed that male and female rats differed in the effects of early
handling (a form of brief beneficial stimulation) on the development of their
corpus callosum. In adulthood (110 days), handled male
rats had significantly greater width of their corpus callosum than non-handled
male controls. The opposite results were observed in
females. Juraska and Kopcik (1988) found that rearing in a complex environment
(post weaning) enhanced the size of the corpus callosum of both male and female
rats, though the magnitude of the effect varied by gender. Moreover,
ultrastructural studies showed that the effects of
early experience were mediated through different mechanisms. Rearing
in the complex environment produced a significant increase in the number of myelinated axons in the corpus callosum of female but not
male rats. In contrast, rearing in the complex
environment markedly increased the diameter of myelinated
axons in the corpus callosum of male rats but had no effect on myelinated axon diameter in females. These
findings lend credence to the hypothesis that early experience can affect the
development of the human corpus callosum and that males
and females may differ to a significant degree in the manner in which the
corpus callosum is affected.
Association
Between Limbic Dysfunction and fMRI
Measures of Cerebellar Vermal
Blood Flow
Childhood
maltreatment has been associated with dissociation, increased prevalence of
abnormal EEGs (Ito, 1998), and development of symptoms suggestive of temporal
lobe epilepsy or limbic irritability (Teicher et al.,
1993). The cerebellum, like the cortex, corpus
callosum, and hippocampus, has a protracted postnatal ontogeny and is markedly
affected by early exposure to corticosteroids (Lauder, 1983).
The cerebellar vermis
appears to play a role in the control of epilepsy or limbic activation (Heath,
1976; Strain et al., 1979; Cooper et al., 1974, 1985; Riklan
et al., 1976). Research by Mason and Harlow (Mason,
1975) has shown that vestibular stimulation during early life (which largely
acts on the cerebellum) markedly attenuates the adverse effects of rearing
without maternal contact. fMRI
was used to assess the relationship between symptoms of limbic irritability and
blood volume in the cerebellar vermis
of young adults with a history of sexual abuse or intense verbal abuse.
T2 relaxometry was used as a novel fMRI
procedure to derive steady-state blood flow measures (Teicher
et al., in press). Although conventional blood
oxygenation level dependent (
Thirty-two
young adults (9M/32F, 18-22 yr) participated, including 15 (3M/12F) with a
history of sexual (n = 12) or verbal (n = 3) childhood trauma exclusive of
physical trauma. Each subject underwent echo-planar fMRI to assess basal blood perfusion in the cerebellar vermis, cerebellar hemispheres, anterior temporal lobe, and entire left
and right cerebral hemispheres. This was accomplished
by collecting a series of 32 "TE stepped" echo-planar images (EPI) in
10 axial slices under resting conditions. A regional
decay curve was generated from median pixel intensity within the ROI at each
value of TE examined to calculate true T2 relaxation time (T2-RT) with high
precision and reproducibility.
There was
a strong association between T2-RT and measures of limbic irritability in both
groups. The correlation was -0.807 (p < .003) in
abused subjects and -0.677 (p < .004) in controls. Slopes
were parallel, but the regression line was much greater in the abused subjects
(p < .0001). Average T2-RT in abused patients was
100.1 ms vs. 91.8 in controls, even after data were controlled for differences
in LSCL-33 scores. Elevated T2-RT measures are
associated with decreased blood volume and neuronal activity.
These findings suggest that early abuse is associated with a functional
deficit in the development of the cerebellar vermis. Blood volume in the vermis increased with greater LSCL-33 scores, possibly
representing an effort by the vermis to modulate and
contain the irritability. Although this is not a brain
region we normally think of as playing an important role in psychiatric symptomatology, there is an enormous convergence of new
data suggesting that abnormalities in the cerebellar vermis may be involved in a wide array of psychiatric
disorders including bipolar and unipolar depression (Fischler et al., 1996; Lauterbach,
1996; Loeber et al., 1999; Beauregard et al., 1998),
schizophrenia (Loeber et al., 1999; Jacobsen et al.,
1997), autism (Courchesne et al., 1991), and ADHD (Berquin et al., 1998; Mostofsky
et al., 1998). The cerebellar vermis
exerts strong modulatory effects on the locus coeruleus, ventral tegmental
area, and substantia nigra,
which are cell body regions for projection of the primary dopamine and norepinephrine pathways (Reis and Golanov,
1997; Snider and Maiti, 1976; Snider et al., 1976).
In
children with ADHD, we found a strong dose-dependent effect of methylphenidate
on T2-RT in the cerebellar vermis
(Anderson et al., 199x). Progressively higher doses of
methylphenidate increase T2-RT. Presumably this occurs through direct effects
of methylphenidate on dopamine transporters in the basal ganglia, and the net
enhancement in dopamine neurotransmission produced by the drug reduced the need
for vermal activation of the substantia
nigra and ventral tegmental
area. Dose-dependent increases in Fos-like
immunoreactivity with acute administration of
d-amphetamine and cocaine have been observed in rat cerebellar
vermis (Klitenick, 1995),
suggesting that abuse-related abnormalities in vermal
development may play some role in the proclivity of individuals with early
abuse to develop drug abuse.
Abuse, Neglect and
the Brain
Licia Rando, M.Ed.
Many people are unaware of the lasting effects child abuse and neglect
can have on children. Young infants, toddlers and
children spend their developmental years and energies adapting their thinking
and actions in order to survive in hostile or negligent environments. This investment in survival robs the body of its
investment in healthful growth and emotional well-being and can manifest itself
in psychological and physical changes. The latest
studies in neurobiology show that the brain itself can be altered in structure
and function. (A)
http://www.liciarando.com/docs/abuse_neglect_and_the_brain.pdf
|
The Biological Psychology
of Dissociative Identity Disorder |
|
Developmental Neurobiology of Dissociative Identity Disorder |
|
Before birth, the human brain develops many
more neurons than it needs. These neurons migrate
to their appropriate positions, and develop dendrites and axons in order
to establish needed connections. Through a
program of apoptosis, or "programmed suicide", approximately
50% of these neurons are eliminated before birth.
From birth to 5 years old, the brain triples in size, largely
due to myelination, which increases speed of information processing.
|
| Critical motor systems develop first, and
the maturation process is much slower in the prefrontal cortex, which
is responsible for executive functions. During
childhood, axons and dendrites proliferate for the purpose of developing
synaptic connections, and are "pruned back" during the transition
to adulthood to reduce redundancy. The final
configuration is determined by cell interactions in the process of gaining
new information and developing skills. Because
of this process of development, the human brain is shaped by early experiences,
and the consequences of childhood abuse may be long lasting and not
easily reversed. |
|
The cascade model 1. Early exposure to
stressors activates stress-response systems and changes their molecular
organization, altering their sensitivity and response bias. 2. The developing
brain is modified by exposure to stress hormones, changing its myelination, programmed cell death, and genesis of new
neurons and synapses. 3. Different brain
regions have different sensitivity, partly due to genetics, gender, timing, rate of development and density of glucocorticoid receptors. 4. Lasting results of
early stress exposure include reduction in left hemisphere development,
decreased right/left hemisphere integration, increased limbic system
irritability and reduced activity of the cerebellar
vermis. 5. These changes
increase vulnerability to neuropsychiatric
consequences, including dissociative identity
disorder. |
| Molecular consequences |
|
Effects of stress hormones on the
developing brain |
| Neurobiological effects of early
abuse |
|
|
| Another study of effects of early exposure
to stress hormones showed a decrease in perfusion of the cerebellar
vermis in patients with repeated sexual abuse,
leading to increased limbic irritability. |
| Functional effects of early maltreatment |
|
|
| DISSOCIATIVE IDENTITY DISORDER |
|
Atypical development of the hippocampus may
make possible the production of dissociative
states, which may be associated with abnormal temporolimbic
EEG activity or limbic irritability. In one
study, patients diagnosed with DID had 5-10 times the rate of EEG abnormality
with paroxysmal spike and sharp waves than that reported in studies
of patients with other psychiatric abnormalities.
|
| Source: |