http://www.annafoundation.org/stwh.pdf

SCARS THAT WON’T HEAL:

THE NEUROBIOLOGY OF CHILD ABUSE

By Martin H.Teicher

Maltreatment at an early age can have enduring negative effects on a child’s brain development and function

In 1994, Boston police were shocked to discover a malnourished four-year-old locked away in a filthy Roxbury apart­ment, where he lived in dreadfully squalid conditions. Worse, the boy’s tiny lands were found to have been horrendously burned. It emerged that his drug-abusing mother had held the child’s hands under a steaming-hot faucet to punish him far eating her boyfriend’s food, despite her instructions not to do so. The ailing young­ster had been given no medical care at all. The disturbing story quickly made na­tional headlines. Later placed in foster care, the boy received skin grafts to help his scarred hands regain their function. But even though the victim’s physical wounds were treated, recent research findings indicate that any injuries inflict­ed to his developing mind may never tru­ly heal.

Though an extreme example, the no­torious case is unfortunately not all that uncommon. Every year child welfare agencies in the U.S. receive more than three million allegations of childhood abuse and neglect and collect sufficient evidence to substantiate more than a mil­lion instances.

It is hardly surprising to us that re­search reveals a strong link between phys­ical, sexual and emotional mistreatment of children and the development of psy­chiatric problems. But in the early 1990s, mental health professionals believed that emotional and social difficulties occurred mainly through psychological means. Childhood maltreatment was understood either to foster the development of intra­psychic defense mechanisms that proved to be self-defeating in adulthood or to ar­rest psychosocial development, leaving a “wounded child” within. Researchers thought of the damage as basically a soft­ware problem amenable to reprogram­ming via therapy or simply erasable through the exhortation “Get over it.”

New investigations into the conse­quences of early maltreatment, including work my colleagues and I have done at McLean Hospital in Belmont, Mass., and at Harvard Medical School, appear to tell a different story. Because childhood abuse occurs during the critical formative time when the brain is being physically sculpted by experience, the impact of se­vere stress can leave an indelible imprint on its structure and function. Such abuse, it seems, induces a cascade of molecular and neurobiological effects that irre­versibly after neural development.

Patients who acknowledged both physi­cal and sexual abuse had average scores 113 percent higher than patients report­ing none. Maltreatment before age 18 had more impact than later abuse, and males and females were similarly affected.

in 1 994 our McLean research team sought to ascertain whether childhood physical, sexual or psychological abuse was associated with~ brain-wave ab­normalities in electroencephalograms (EEG5), which provide a more direct measure of limbic irritability than our check­list. We reviewed the records of 115 con­secutive admissions to a child and ado­lescent psychiatric hospital to search for a link. We found clinically significant brain-wave abnormalities in 54 percent of patients with a history of early trauma but in only 27 percent of nonabused patients. We observed EEG anomalies in 72 per­cent of those who had documented histo­ries of serious physical and sexual abuse.

• The irregularities arose in frontal and temporal brain regions and, to our sur­prise, specifically involved the left hemisphere rather than both sides, as one would expect.

Our findings dovetailed with a 1978 EEG study of adults who were victims of incest. The study’s author, Robert W. Davies of the Yale University School of Medicine, and his team had found that 77 percent exhibited EEG abnormalities and 27 percent experienced seizures.

Subsequent work by other investiga­tors using magnetic resonance imaging (MRI) technology has confirmed an as­sociation between early maltreatment and reductions in the size of the adult hippocampus. The amygdala may he smaller as well. In 1997 J. Douglas Brem­ner, then at the Yale University School of Medicine, and his colleagues compared MM scans of 17 adult survivors of child­hood physical or sexual abuse, all of whom had posttraumatic stress disorder (PTSD), with 17 healthy subjects matched for age, sex, race, handedness, years of ed­ucation, and years of alcohol abuse. The left hippocampus of abused patients with PTSD was, on average, 12 percent small­er than the hippocampus of the healthy control subjects, but the right hippocampus was of normal size, Not surprisingly, given the important role of the hippocampal function, these patients scored lower on verbal memory tests than the nonabused group.

In 1997 Murray B. Stein of the Uni­versity of California at San Diego also found left hippocampal abnormalities in 21 adult women who had been sexually abused as children and who had1~TSD or dissociative identity disorder (also called multiple personality disorder, a condition thought by some researchers to be common in abused females). Stein deter­mined that in these women the volume of the left hippocampus was significantly re­duced hut that the right hippocampus was relatively unaffected. In addition, he found a clear correspondence between the degree of reduction in hippocampus size and the severity of the patients’ dis­sociative symptoms. In 2001 Martin Driessen of Gilead Hospital in Bielefeld, Germany, and his colleagues reported a 16 percent reduction in hippocampus size and an 8 percent reduction in amygdala size in adult women with borderline personality disorder and a history of childhood maltreatment.

On the other hand, when Michael D. De Beilis and his colleagues at the Uni­versity of Pittsburgh School of Medicine carefully measured MRI images of the hippocampus in 44 maltreated children with PTSD and 61 healthy control sub­jects in 1999, they failed to observe a significant difference in volume. My McLean colleagues Susan Ander­sen and Ann Polcari and I obtained sim­ilar results in our recently completed vol­umetric analysis of the hippocampus in 18 young adults (18 to 22 years of age) with a history of repeated forced sexual abuse accompanied by fear or terror, who were compared with 19 healthy age ­matched controls. Unlike in previous studies, the control subjects were not pa­tients but were recruited from the gener­al public and had fewer mental health problems. We observed no differences in h hippocampal volume. Like Driessen’s group, however, we did find a 9.8 percent average reduction in the size of the left arnygdala, which correlated with feelings of depression and irritability or hostili­ty. We asked ourselves why the hippocampus was smaller in abused subjects in studies from Bremner’s, Stein’s and Dreissen’s groups but normal in Dc Eel­lis’s and in our own investigations. Often several possible answers, the most likely is that stress exerts a very gradual influ­ence on the hippocampus, so adverse ef­fects may not be discernible at a gross anatomical level until people get older.

Moreover, animal studies by Bruce S. McLwen of the Rockefeller University and Robert M. Sapolsky of Stanford Uni­versity had previously demonstrated the marked vulnerability of the hippocampus to the ravages of stress. Not only is the hippocampus particularly susceptible be­cause it develops slowly, it also is one of the few brain regions that continues to grow new neurons after birth. Further, it has a higher density of receptors for the stress hormone cortisol than almost any other area of the brain. Exposure to stress hormones can significantly change the shape of the largest neurons in the hip­pocampus and can even kill them. Stress also suppresses production of the new granule cells (small neurons), which nor­mally continue to develop after birth.

Experiments with rats by Christian Caldji, Michael J. Meaney of McGill University and Paul M. Plotsky of Emory University have shown that early stress reconfigures the molecular organization of these regions. One major result is the alteration of the protein subunit structure of GABA receptors in the amygdala. These recep­tors respond to gamma aminobutyric acid, the brain’s primary inhibitory neu­rotransmitter, and GABA attenuates the electrical excitability of neurons. Re­duced function of this neurotransmitter produces excessive electrical activity and can trigger seizures. This discovery provides an elegant molecular explanation for our findings of LLG abnormalities and limbic irritability in patients with childhood abuse.

Left-Side Problems

THE EFFECT on the limbic system was only the most expected consequence of childhood trauma. We were intrigued, however, by our earlier observation that ill-treatment was associated with LEG abnormalities in the left hemisphere. This in­spired us to examine the effect of early abuse on the development of the left and right hemispheres. We chose to use LEG coherence, a sophisticated quantitative analysis method that provides evidence about the brain’s microstructure—its wir­ing and circuitry. Conventional LEG, in contrast, reveals brain function. The LEG coherence technique accomplishes its task by generating a mathematical measure of the degree of cross-correlation among the elaborate neuronal interconnections in the cortex that process and modify the brain’s electrical signals. In general, ab­normally high levels of LEG coherence are evidence of diminished development among these neuron interchanges.

Our research team used this technique in l997 to compare 15 healthy volunteers with 15 child and adolescent psychiatric patients who had a confirmed history of intense physical or sexual abuse. Coher­ence measures showed that the left cortex of the healthy control subjects were more developed than the right cortex, a result that is consistent with what is known about dominant hemisphere anatomy— that is, right-handed people tend to be left-cortex dominant. The maltreated pa­tients, however, were notably more de­veloped in the right cortex than the left, even though all were right-handed and hence left dominant. The right hemi­spheres of abused patients had developed as much as the right hemispheres of the control subjects, but their left hemi­spheres lagged substantially behind. This anomalous result showed up regardless of the patient’s primary diagnosis. And al­though the effect extended throughout the entire left hemisphere, the temporal regions were most affected, which sup­ported our original hypothesis.

The left hemisphere is specialized for perceiving and expressing language, whereas the right hemisphere specializes in processing spatial information and in processing and expressing emotions— particularly negative emotions. We had wondered whether mistreated children might store their disturbing memories in the right hemisphere and whether recol­lecting these memories might preferen­tially activate the right hemisphere.

To test this hypothesis, Fred Schiffer worked in my laboratory at McLean in 1995 to measure hemispheric activity in adults during recall of a neutral memory and then during recall of an upsetting early memory. Those with a history of abuse appeared to use predominantly their left hemispheres when thinking about neutral memories and their right when recalling an early disturbing mem­ory. Subjects in the control group used both hemispheres to a comparable degree for either task, suggesting that their re­sponses were more integrated between the two hemispheres, information exchange between the two hemi­spheres, the corpus callosum. In 1997Andersen and I collaborated with Jay Giedd of the National Institute of Mental Health to search for the posited effect. Together we found that in boys who had been abused or neglected, the middle parts of the corpus callosum were significantly smaller than in the control groups. Fur­thermore, in boys, neglect exerted a far greater effect than any other kind of mal­treatment in girls; however, sexual abuse was a more powerful factor, associated with a major reduction in size of the mid­dle parts of the corpus callosum. These re­sults were replicated and extended in 1999 by De Pellis. Likewise, the effects of early experience on the development of the corpus callosum have been confirmed by research in primates by Mara M. Sanchez of Emory.

Our latest finding had its roots in the seminal studies of Harry F. Harlow of the University of Wisconsin—Madison. In the 1950s, Harlow compared monkeys raised by their mothers with monkeys reared by wire or terrycloth surrogate mothers. Monkeys raised with the surro­gates became socially deviant and highly aggressive adults. Working with Harlow, W. A. Mason of the Delta Primate Cen­ter in Louisiana discovered that these consequences were less severe if the sur­rogate mother was swung from side to side. J. W. Prescott of the National Insti­tute of Child Health and Human Devel­opment hypothesized that this movement would be conveyed to the cerebellum, particularly the middle part, called the cerebellar vermis, located at the back of the brain just above the brain stem. Among other functions, the vermis mod­ulates the brain-stem nuclei that control the production and release of the neuro­transmitters norepinephrine and dopa­mine. Like the hippocampus, this part of the brain develops gradually and contin­ues to create neurons after birth. It has an even higher density of receptors for stress hormones than the hippocampus, so ex­posure to such hormones can strongly

af­fect its development.

Abnormalities in the cerebellar ver­mis have recently been reported to be as­sociated with various psychiatric disor­ders, including manic-depressive illness, schizophrenia, autism and attention­ deficit hyperactivity disorder. These mal­adies emerge from genetic and prenatal factors, not childhood mistreatment, but the fact that vermal anomalies seem to sit at the core of so many psychiatric condi­tions suggests that this region plays a crit­ical role in mental health.

Dysregulation of the vermis-controlled neurotransmitters norepinephrine and dopamine can produce symptoms of de­pression, psychosis and hyperactivity as well as impair attention. Activation of the dopamine system has been associated with a shift to a more left hemisphere— biased (verbal) attentional state, whereas activation of the norepinephrine system shifts attention to a more right hemi­sphere—biased (emotional) state. Perhaps most curiously, the vermis also helps to regulate electrical activity in the limbic system, and vermal stimulation can sup­press seizure activity in the hippocampus and amygdala.

R. G. Heath, working at Tulane Uni­versity in the 1950s, found that Harlow’s monkeys had seizure foci in their fastigial nuclei and hippocampus. In later work with humans, he found that electrical stimulation of the vermis reduced the fre­quency of seizures and improved the men­tal health in a small number of patients with intractable neuropsychiatric disor­ders. This result led my colleagues and me to speculate whether childhood abuse could produce abnormalities in the cere­bellar vermis that contributed to psychi­atric symptoms, limbic irritability and gradual hippocampal degeneration.

To begin to test this hypothesis, Carl M. Anderson recently worked in tandem with me and with Perry Renshaw at the Brain Imaging Center at McLean. An­derson used T2-relaxometry methods, a new Mill-based functional imaging tech­nique we developed. For the first time, we can monitor regional cerebral blood flow at rests without the use of radioactive trac­ers or contrast dyes.

When the brain is resting, the neu­ronal activity of a region closely match­es the amount of blood that area receives to sustain this activity. Anderson found a striking correlation between the activity in the cerebellar vermis and the degree of limbic irritability indicated by my TLE ­related question checklist in both healthy young adult controls and young adults

with a history of repeated sexual abuse. At any level of limbic symptomatol­ogy, however, the amount of blood flow in the vermis was markedly decreased in the individuals with a history of trauma. Low blood flow points to a functional impairment in the activity of the cerebellar vermis. On average, abused patients had higher checklist scores presumably because their vermis could not activate sufficiently to quell higher levels of lim­bic irritability.

Together these findings suggest an in­triguing model that explains one way in which borderline personality disorder can emerge. Reduced integration between the right and left hemispheres and a smaller corpus callosum may predispose these pa­tients to shift abruptly from left- to right-dominated states with very different emo­tional perceptions and memories. Such polarized hemispheric dominance could cause a person to see friends, family and co-workers in an overly positive way in one state and in a resoundingly negative way in another—which is the hallmark of this disorder. Moreover, limbic electrical irritability can produce symptoms of ag­gression, exasperation and anxiety. Ab­normal LEG activity in the temporal lobe is also often seen in people with a greatly increased risk for suicide and self-destructive behavior.

Adaptive Detriment

OUR TEAM INITIATED this research with the hypothesis that early stress was a toxic agent that interfered with the nor­mal, smoothly orchestrated progression of brain development, leading to endur­ing psychiatric problems. Frank W. Put­nam of Children’s Hospital Medical Cen­ter of Cincinnati and Bruce D. Perry of the Alberta Mental Health Board in Canada have now articulated the same hypothe­sis. I have come to question and reevalu­ate our starting premise, however, hu­man brains evolved to be molded by ex­perience, and early difficulties were routine during our ancestral develop­ment.

Is it plausible that the developing brain never evolved to cope with exposure to maltreatment and so is damaged in a nonadaptive manner? This seems most un­likely. The logical alternative is that exposure to early stress generates molecular and neurobiological effects that alter neur­al development in an adaptive way that prepares the adult brain to survive and re­produce in a dangerous world.

What traits or capacities might be beneficial for survival in the harsh condi­tions of earlier times? Some of the more obvious are the potential to mobilize an intense fight-or-flight response, to react aggressively to challenge without undue hesitation, to be at heightened alert for danger and to produce robust stress re­sponses that facilitate recovery from in­jury. In this sense, we can reframe the brain changes we observed as adaptations to an adverse environment.

Although this adaptive state helps to take the affected individual safely through the reproductive years (and is even likely to enhance sexual promiscuity, which are critical for evolutionary success, it comes at a high price.

McEwen has recently the­orized that overactivation of stress

response systems, a reaction that may be necessary for short-term survival, increas­es the risk for obesity, type II diabetes and hypertension; leads to a host of psychi­atric problems, including a heightened risk of suicide; and accelerates the aging and degeneration of brain structures, in­cluding the hippocampus.

We hypothesize that adequate nurtur­ing and the absence of intense early stress permits our brains to develop in a manner that is less aggressive and more emotion­ally stable, social, empathic and hemispherically integrated. We believe that this process enhances the ability of social ani­mals to build more complex interperson­al structures and enables humans to better realize their creative potential

Society reaps what it sows in the way it nurtures its children. Stress sculpts the brain to exhibit various antisocial, though adaptive, behaviors. Whether it comes in the form of physical, emotional or sexu­al trauma or through exposure to war­fare, famine or pestilence, stress can set off a ripple of hormonal changes that permanently wire a child’s brain to cope with a malevolent world. Through this chain of events, violence and abuse pass from generation to generation as well as from one society to the next. Our stark conclusion is that we see the need to do much more to ensure that child abuse does not happen in the first place, because once these key brain alterations oc­cur, there may be no going back.

THE AUTHOR: Martin H. Teicher is an associate professor psychiatry at Harvard Medical School, director of the Developmental Biopsychiatry Research Program at McLean Hospital in Belmont, Mass., and chief of the Developmental Psychopharmacology Laboratory at the Mailman Research Center at McLean.

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This article is depressing, sort of. Does that mean if we've been abused, we'll never heal? And never have a good relationship with ourselves, let alone with others? how sad! Is there any way out?

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