Psychiatr Clin N Am 25 (2002) 397–426

Developmental neurobiology
of childhood stress and trauma
Martin H. Teicher, MD, PhDa,b,c,*,
Susan L. Andersen, PhDa,c, Ann Polcari, PhDb,
Carl M. Anderson, PhDa,b,d, Carryl P. Navalta, PhDa,b
a
Department of Psychiatry, Harvard Medical School, 25 Shattuck Street,
Boston, MA 02115, USA
b
Developmental Biopsychiatry Research Program, McLean Hospital,
115 Mill Street, Belmont, MA 02478, USA
c
Laboratory of Developmental Psychopharmacology,
Mailman Laboratories for Psychiatric Research,
McLean Hospital, 115 Mill Street, Belmont, MA 02478, USA
d
Brain Imaging Center, McLean Hospital 115 Mill Street, Belmont, MA 02478, USA

Neither youth nor innocence provides protection from the ravages of fate.
Exposure to traumatic stress can occur at any point along the developmental
continuum. Considerable progress has been made in unraveling the nature of
the stress response and in understanding the neurobiological and neuroendo-
crine underpinnings of post-traumatic stress disorder (PTSD) in adults. Expo-
sure to intense or persistent stress during childhood is another matter. Because
it occurs during a time when the brain is undergoing enormous change, the
impact of severe stress may leave an indelible imprint on the structure and
function of the brain [1]. Indeed, the mammalian brain is designed to be
sculpted into its final configuration by the effects of early experience [2].
Hence, an understanding of the neurobiology of childhood trauma must begin
with an understanding of the effects of early stress on brain development.
This article does not focus exclusively on PTSD because most children
exposed to traumatic events never develop PTSD. Deblinger et al. [3] found
that only 6.9% of psychiatrically hospitalized children with a history of phy-
sical abuse and 20.7% with a history of sexual abuse met diagnostic criteria
for PTSD. Famularo et al. [4] found that only 35% of severely maltreated
and psychologically traumatized children who were removed from parental
custody because of the trauma actually met strict criteria for PTSD. Widom

* Corresponding author.
E-mail address: [email protected] (M.H. Teicher).

0193-953X/02/$ - see front matter Ó 2002, Elsevier Science (USA). All rights reserved.
PII: S 0 1 9 3 - 9 5 3 X ( 0 1 ) 0 0 0 0 3 - X
398 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

[5] reported a 37.5% lifetime prevalence for emergence of PTSD for victims
of substantiated childhood abuse and neglect. This is not necessarily a mat-
ter of resilience; Kiser et al. [6] found that abused children and adolescents
who did not develop PTSD actually exhibited more anxiety, depression,
externalizing behaviors, and more overall problems than children who did
develop PTSD. Similarly, Glod et al. [7] found that psychiatrically hospita-
lized abused children without PTSD had more agitated and disrupted sleep
than abused children with PTSD. These findings suggest that PTSD criteria
formulated and validated in adults do not necessarily adequately describe
the psychiatric impact of exposure to childhood trauma and do not necessa-
rily identify which children are most adversely affected by trauma. Hence,
we focus on the developmental neurobiological effects of severe stress with
or without concomitant PTSD.
This article synthesizes two lines of research into a specific, testable,
empirical model that outlines a cascade of alterations likely to follow from
severe exposure to stress before the onset of puberty. One line of investigation
focuses on the effects of early experience on the development of the mamma-
lian brain at the molecular, cellular, and behavioral level. The second line of
investigation examines the enduring effects of childhood maltreatment on
neuromorphology, functional brain activity, and neuropsychiatric health.

Overview of postnatal brain development

The human brain contains billions of neurons and trillions of synaptic
interconnections. Genes dictate the basic architecture, but there is insuf-
ficient genetic information to detail the specific wiring. The final form and
connection patterns are sculpted by experience.
The brain develops through a series of overlapping stages. Before birth,
the developing brain contains two to three times the full adult complement
of immature neurons, which migrate to their final positions and arborize in
an attempt to establish appropriate connections [8]. In a striking turn of
events, more than 50% of these neurons are eliminated before birth in a pro-
cess known as cell death or apoptosis [9]. Fluctuations in corticosteroid levels
play a critical role in the initiation and termination of this process [10].
Neurogenesis (production of new neurons) ceases in most brain regions
at birth, although stem cells continue to generate neurons within the hippo-
campal dentate gyrus throughout life [11]. From birth to 5 years of age, the
brain triples in mass. Much of the gain in brain size stems from the vigorous
myelination of fiber tracts. Myelination markedly increases the speed of
information exchange and is at least partially responsible for the emergence
of our rich behavioral repertoire. The myelination rate varies markedly
between brain regions. Critical motor systems myelinate at an early age,
whereas the process is quite protracted in the prefrontal cortex. Gender also
affects myelination rate in some regions, such as the corpus callosum and
hippocampus [12].
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 399

During childhood, there is a marked expansion of axonal and dendritic

arborizations and a rapid increase in synaptic contacts. This process mirrors
the earlier overproduction and elimination of neurons. There is a substantial
overproduction of synapses [13–15], receptors [16,17], dendrites [18], and
axons [19] that are pruned back during the transition into adulthood with-
out cell death. This is the fundamental developmental strategy of the mam-
malian central nervous system and has been observed in humans [13,17],
primates [15,16,20], and rodents [21,22].
Overproduction and elimination specifically affects excitatory synapses
[23] and the density of glutamate [24], dopamine [17], and neurotensin [25]
receptors. Rate and degree of pruning vary from region to region. We found
that, in the nigrostriatal system of rats, dopamine receptors prune immedi-
ately after the onset of puberty and prune in early adulthood in the pre-
frontal cortex but do not prune in the limbic connections to the nucleus
accumbens [22,26]. There are also gender differences. Dopamine receptors
are markedly overproduced and pruned in the striatum of male but not
female rats [21]. This is probably also true in humans. Giedd et al. [27] found
that there was a substantial postpubertal reduction in the size of the stria-
tum (caudate and putamen) in boys but not in girls. We suspect that sex dif-
ferences in striatal development are responsible for gender differences in the
prevalence of attention-deficit/hyperactivity disorder (ADHD) and Tourette
syndrome [28]. One consequence of pruning may be the elimination of speci-
fic forms of synaptic circuitry. For instance, dopamine synthesis modulating
autoreceptor function is present in the prefrontal cortex before puberty but
is absent in adulthood [29]. Furthermore, an interneuron circuit stimulates
dopamine synthesis in the immature prefrontal cortex but not in the adult
prefrontal cortex [30]. Feinberg [31] postulated that abnormalities in the
pruning process are responsible for the emergence of schizophrenia. Alter-
natively, normal pruning may remove redundancy and unmask an
earlier developmental defect, leading to the emergence of symptoms in late
adolescence or early adulthood [32].

Why does the brain overproduce and prune synapses,

receptors, and neural contacts?
Jacobson [33] proposed a theory of neuronal modification by selective
depletion, which states that overproduction of synapses is genetically pro-
grammed and that the final configuration of the circuitry occurs by elimina-
tion of synapses based on cell interactions. These interactions reduce the
degree of initial programmed redundancy and selectively promote the develop-
ment of neuronal innervation patterns that can coexist because they are
mutually compatible or interdependent. Jacobson [33] proposed that this
process results in increased matching of the functions of the nervous system
with the conditions of the outside world. In our view, the developing mam-
malian brain is a rich neural network whose primary task is to acquire new
400 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

information and develop skills. This rich network performs slowly, at great
metabolic expense, and requires long periods of deep sleep [31]. At a certain
stage of development, excess and redundant connections are sculpted to
speed the performance of acquired skills and to reduce metabolic demands
and sleep requirements while sacrificing a certain degree of plasticity.
Because the brain is designed to develop in this fashion, it is intrinsically
shaped by the effects of early experience, and the consequences of inade-
quate or deleterious experience may be enduring and irreversible.

Basic outline of the cascade model

The cascade model is built on five fundamental premises. First, exposure
to stress early in life activates stress-response systems and fundamentally
alters their molecular organization to modify their sensitivity and response
bias. Second, exposure of the developing brain to stress hormones affects
myelination, neural morphology, neurogenesis, and synaptogenesis. Third,
different brain regions differ in their sensitivity, which depends, in part, upon
genetics, gender, timing, rate of development, and density of glucocorticoid
receptors. Fourth, there are enduring functional consequences that include
attenuated left hemisphere development, decreased right/left hemisphere
integration, increased electrical irritability within limbic system circuits, and
diminished functional activity of the cerebellar vermis. Fifth, there are asso-
ciated neuropsychiatric consequences and vulnerabilities, which lead to an
enhanced risk for the development of PTSD, depression, borderline person-
ality disorder, dissociative identity disorder, and substance abuse.

Molecular consequences of early stress

The first step in the cascade is the enduring effects of stress on the mole-
cular components of the stress-response system. There are three major
pillars to this system. One pillar involves the hippocampus and the hypotha-
lamic-pituitary-adrenal (HPA) axis and is intimately involved in the feed-
back regulation of cortisol. This is an indispensable stress hormone, which
mobilizes energy stores; potentiates the release of adrenaline; increases car-
diovascular tone; and inhibits growth, immune, and inflammatory responses
[34]. The second pillar involves the amygdala, locus coeruleus, adrenal
gland, and sympathetic nervous system. This is the noradrenergic and adren-
aline response to stress, which is crucial for enhancing and directing blood
flow, increasing awareness, and mobilizing a fight-or-flight response. A third
and less explored stress response system involves the vasopressin–oxytocin
peptide prohormone family. Vasopressin is predominantly involved in fluid
retention during stress caused by hemorrhage or severe fluid deprivation,
although vasopressin and oxytocin also trigger the release of adrenocortico-
tropin hormone (ACTH) from the pituitary gland.
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 401

A series of seminal studies from the laboratories of Plotsky and Meaney

have shown that early stress produces enduring changes in the molecular
organization of the stress-response systems. In essence, they are pro-
grammed by experience [35]. Effects of stress on developing rats are largely
mediated through alterations in maternal behavior. Very brief handling is a
beneficial stimulus [35] largely because it increases rates of maternal licking
and grooming [36]. Prolonged periods of maternal separation are stressful
largely because they attenuate maternal licking and grooming [36].
Prolonged maternal separation, exposure to endotoxins, and less attentive
nursing (i.e., neglect) are all stressors that alter the molecular composition of
the gamma-aminobutyric acid (GABA)-benzodiazepine supramolecular
complex, resulting in the attenuated development of central benzodiazepine
and high-affinity GABA-A receptors in the amygdala and locus coeruleus
(LC) [37,38]. Prolonged maternal separation and less attentive nursing also
elevates corticotropin-releasing hormone (CRF) mRNA levels projecting
from the amygdala to the LC and diminishes a2 noradrenergic receptor den-
sity in the LC [38], which provides feedback inhibition of noradrenergic neu-
rons. The net effect is enhanced fearfulness and anxiety caused by diminished
GABAergic inhibition of the amygdala that is conveyed by CRF projections
from the amygdala to the LC and by projections from the LC to noradrener-
gically innervated regions throughout the brain [38]. Furthermore, prolonged
stress or maternal inattention attenuates development of glucocorticoid (GC)
receptors in the hippocampus and diminishes negative feedback regulation of
cortisol and augments CRF and vasopressin mRNA levels in the hypothala-
mus, resulting in enhanced stress production of ACTH and corticosterone
[39]. In short, early stress programs and primes the mammalian brain to be
more fearful and to have an enhanced noradrenergic, corticosteroid, and vaso-
pressin response to stress.

Stress hormone effects on the developing brain

The second stage of the cascade model centers on the effects of increased
activation of the stress hormone systems on the developing brain. In parti-
cular, corticosteroids have dramatic and profound effects on the devel-
opmental process. Research in laboratory animals has shown that GC
administration during early life permanently reduces brain weight and DNA
content [40], suppresses postnatal neural mitosis of granule cells in the cere-
bellum and dentate gyrus [41], and interferes with myelination, a process
that depends on glial cell division [42]. GCs have also been shown to alter
neural morphogenesis by reducing the number of dendritic spines in various
brain regions [43]. Behavioral consequences of early GC administration that
are discernible in juvenile and adult rats include alterations in social behav-
ior [44] and deficits in active avoidance learning [45]. A single dose of
corticosteroid during early development also delays the maturation of audi-
tory-, visual-, and somatosensory-evoked potentials [43].
402 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

Normally, the developing mammalian brain is protected from exposure

to high levels of exogenous corticosteroids. There is a developmental time
frame (the stress hyporesponsive period) in which basal corticosteroid
levels are low and a variety of stressors fail to elicit a strong corticosteroid
response, presumably to protect the brain from the effects of exposure [34].
However, certain stressors can effectively elicit a stress hormone response
[46–49], and this can set into motion a large number of effects on neural
division, differentiation, and myelination.
One puzzle in understanding the impact of stress hormones on brain
development is the absence of known consequences of childhood treatment
with very high doses of corticosteroids for asthma or arthritis. We suspect
that adverse effects of early stress on human brain development are not
simply the consequence of increased exposure to cortisol. The suppressive
action of GCs on cell proliferation is not direct but occurs through an
N-methyl-D-aspartate (NMDA) receptor-dependent glutamate excitatory
pathway [50]. We hypothesize that stress affects brain development via the
activation of multiple pillars of the stress response. Both norepinephrine and
vasopressin synergistically potentiate the excitatory effects of glutamate on
NMDA receptors [51,52]. Hence, concerted activation of multiple systems
may have much greater impact than exogenous administration of a single
hormone.

Neurobiological effects of early stress or childhood abuse

The following section summarizes preclinical studies that delineate the
effects of early stress on specific brain regions found to be vulnerable. Clin-
ical studies then review the effects of childhood maltreatment on the devel-
opment of these regions in humans. The most vulnerable brain regions
include those that develop slowly during the postnatal period, have a high
density of GC receptors, and continue to generate new neurons after birth.

Hippocampus
Preclinical studies have demonstrated the marked vulnerability of the
hippocampus to the ravages of stress. This region has a protracted ontog-
eny, persistent postnatal neurogenesis [53], and a high density of GC recep-
tors (e.g., [54,55], but see [56]). Exposure to stress or corticosteroids can
markedly alter pyramidal cell morphology and can even produce pyramidal
cell death [57]. Stress also suppresses production of new granule cells [53],
and we have found that early stress prevents the normal prepubertal over-
production of synapses in CA1 and CA3 but does not prevent pruning,
which leads to an enduring deficit in synaptic numbers (Anderson et al.
2000, unpublished data).
Bremner et al. [58] and Stein [59] reported a reduction in left hippocampal
volume in adults with childhood trauma and a current diagnosis of PTSD or
dissociative identity disorder. Stein [59] found that there was a 5% reduction
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 403

in left hippocampal volume and that the degree of hippocampal size cor-
related with symptoms of dissociation and the magnitude of cortisol suppres-
sion on the low-dose dexamethasone suppression test. Bremner et al. [58]
reported a 12% reduction in left hippocampal volume but, unlike other
researchers, did not conduct a complete volumetric analysis of the hippo-
campus but examined only the anterior portions. More recently, De Bellis
et al. [60] conducted a detailed volumetric analysis of the hippocampus in
44 maltreated children with PTSD and 61 healthy control subjects. They
failed to observe a significant difference in hippocampal volume. We con-
ducted a complete 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 and compared these with 19 healthy age-
matched control subjects. Unlike in previous studies, the study subjects were
not patients but were recruited from a community sample. At the time of
assessment, only one subject met the criteria for PTSD, although six had
a prior history. No subject had a history of drug use or significant alcohol
consumption. No differences were observed in left or right hippocampal
volume, and there were no significant associations between hippocampal
volume, psychiatric symptomatology, or memory function (Navalta et al.
2000, unpublished data).
Why might Bremner et al. [58] and Stein [59] have observed reduced hippo-
campal volume in adults with a history of childhood abuse and current
PTSD, whereas our group and DeBellis et al. [60] failed to find any differ-
ences? One possible answer is that PTSD exerts a very gradual effect on hip-
pocampal morphology so that the adverse effects are not discernible in
children or young adults [61]. Another possible answer is that reduced hippo-
campal size may be an artifact of the high levels of alcohol and substance
abuse that often occurs in adults with PTSD. Indeed, De Bellis et al. [62]
found that adolescent-onset alcohol abuse was associated with decreased
hippocampal volume. Bremner et al. [58] and Stein [59] tried to statistically
control for this factor, but this does not exclude the possibility that alcohol
abuse served as a catalyst to augment the impact of childhood trauma and
PTSD [63]. Another intriguing possibility is that reduced hippocampal size
may not be a result of childhood abuse or even a risk factor for the emer-
gence of PTSD but may be a risk factor for the persistence of PTSD into
adulthood.

Amygdala
The amygdaloid nuclei are some of the most sensitive structures in the
brain for the emergence of kindling, an important phenomenon in which
repeated intermittent stimulation produces greater and greater alteration
in neuronal excitability that may eventually result in seizures [64,65]. How-
ever, the emergence of seizure activity is not critical; kindling results in long-
term alterations in neuronal excitability that can have major impact on
behavioral control [65]. As noted above, early stress attenuates development
404 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

of the GABA-A supramolecular complex in the amygdala, reducing the den-

sity of both central benzodiazepine receptors and high-affinity GABA-A
receptors [37,38]. GABA is a crucial inhibitory neurotransmitter that at-
tenuates electrical excitability, and diminished GABA neurotransmission,
which occurs during benzodiazepine or alcohol withdrawal, is associated
with neuronal irritability and seizure susceptibility. In addition to the effects
of stress on the GABA-benzodiazepine system, there are enduring effects on
serotonin and dopamine innervation. Robbins et al. [66,67] and our group
[68] found that maternal separation stress increased dopamine levels and
diminished serotonin levels in the amygdala and the nucleus accumbens.
Abnormalities in amygdala or hippocampal development and a dimin-
ished density of central benzodiazepine and high-affinity GABA-A receptors
may lead to the emergence of temporal lobe or limbic seizure-like acti-
vity. Our initial studies on the potential impact of childhood abuse on
brain development focused on the emergence of limbic system dysfunction
(irritability) as likely sequelae. We created the limbic system checklist-33
(LSCL-33) to rate the occurrence of symptoms that often emerge during
temporal lobe seizures (e.g., perceptual distortions, brief hallucinatory
events, motor automatisms, and dissociative phenomena), postulating that
stress effects or kindling of limbic structures may produce these symptoms
in the absence of actual seizures [69]. We found that adult outpatients with
a self-reported history of physical or sexual abuse had increased LSCL-33
scores that were dramatically elevated in patients with a history of combined
abuse [69]. Subsequently, we found that psychiatrically hospitalized child-
ren with a history of abuse had a twofold increased incidence of clinically
significant EEG abnormalities [70]. The abnormalities were frontotemporal
in origin and consisted of spikes, sharp waves, or paroxysmal slowing.
Surprisingly, the entire increase in incidence was caused by alterations with-
in the left hemisphere. There was also a strong behavioral association
between the presence of EEG abnormalities and history of self-destructive
or violent behaviors. Children with a Department of Social Services con-
firmed diagnosis of severe physical or sexual abuse (but not head trauma) had
a 72% incidence of EEG abnormalities. Interestingly, Davies [71] found the
same high rate of EEG abnormalities in a sample of incest survivors,
although he did not believe that this was a consequence of the adverse child-
hood experience but rather was a risk factor for being molested [71].
Imaging studies by Bremner et al. [58], Stein [59], and De Bellis et al. [60]
failed to find any differences in amygdala volume in abuse survivors with
PTSD versus control subjects. Interestingly, although we did not find a
reduction in hippocampal volume in young adults with a history of repeated
childhood abuse, we did find a 9.8% reduction in the size of the left amyg-
dala (P < .02). Left amygdala size correlated inversely with self-report ratings
of depression and irritability (Navalta et al. 2000, unpublished data). Redu-
ced amygdala size has previously been reported in depressed adults [72]. Our
sample differed from the previous studies in the low incidence of PTSD or
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 405

psychopathology despite the substantial history of abuse. Because amygdala

overactivation may be a critical factor in PTSD [73], there is an alternative
explanation for our observation. A smaller amygdala may provide protec-
tion from the emergence of PTSD following childhood trauma or may facil-
itate recovery from PTSD.

Corpus callosum and hemispheric integration

Myelinated regions, such as the corpus callosum, are also potentially vul-
nerable to the impacts of early exposure to excessive levels of stress hor-
mones, which suppress glial cell division critical for myelination [42].
Pioneering studies by Denenberg showed that corpus callosum size was
markedly affected by early experience and that the effects were gender
dependent [74]. Handled male rats had significantly greater width of their
corpus callosum than nonhandled male control rats, specifically in the mid-
dle portions. Sanchez et al. [56] found that rearing male monkeys in an iso-
lating environment also attenuated the development of the corpus callosum,
and diminished size was associated with defects in certain learning tasks.
Teicher et al. [75] provided the first indication that the corpus callosum
may be adversely affected by childhood trauma, noting a marked reduction
in the middle portions of the corpus callosum in child psychiatric inpatients
(particularly boys) with a substantiated history of abuse (excluding head
injuries) or neglect versus contrast control subjects. This observation was
replicated and extended in an important study by De Bellis [60], who showed
that reduced corpus callosum size was the most prominent anatomic finding
they observed in children with a history of abuse and PTSD. Boys were more
affected than girls. More recently, we found that the corpus callosum in boys
is particularly vulnerable to the effects of neglect. The corpus callosum in
girls seems to be more vulnerable to the adverse effects of sexual abuse [76].
Reduced size of the corpus callosum has been associated with diminis-
hed communication between the hemispheres [77]. Schiffer et al. [78] used
auditory-evoked potentials to study laterality and hemispheric integration
of memory in adults with a history of childhood maltreatment who were all
currently well functioning and who had no active Axis I diagnosis. Subjects
were asked to actively recall a neutral or work-related memory and were
then asked to recall with affect a disturbing memory from childhood. In nor-
mal individuals, both hemispheres appeared to be equally involved in the
recall of these memories. In adults with a history of childhood trauma, there
was a dramatic difference: During recall of the neutral memory, there was a
marked suppression of the evoked potential response over the left hemi-
sphere indicative of increased left hemisphere processing. During recall of
the disturbing memory, there was a robust shift in laterality with the evoked
potential response being suppressed over the right hemisphere, which is indi-
cative of enhanced right hemisphere activation. This suggests that early
maltreatment was associated with increased hemispheric laterality and de-
creased hemispheric integration.
406 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

Cerebellar vermis
Another brain region that should be extraordinarily sensitive to the effects
of early maltreatment is the cerebellar vermis. Like the hippocampus, the ver-
mis has a protracted period of postnatal development and may produce gran-
ule cells postnatally [79]. The vermis also has the highest density of GC
receptors during development, exceeding that of the hippocampus [56,80,81],
and may be particularly vulnerable to the effects of stress hormones [43,82].
Anderson et al. [83] studied the association between activity in the cere-
bellar vermis and symptoms of limbic irritability. Vermal activation was
assessed using T2 relaxometry, a novel functional magnetic resonance ima-
ging (f MRI) procedure that provides an indirect index of basal cerebral
blood volume [84]. Unlike bold f MRI, this technique does not utilize an acti-
vation procedure and provides an index of relative blood volume that corre-
lates well with the assessment of resting cerebral blood volume using dynamic
susceptibility contrast mapping [85]. There was a striking correlation between
activity in the cerebellar vermis and the degree of limbic irritability on the
LSCL-33 in both healthy young adult control subjects and young adults with
a history of repeated sexual abuse. However, at any level of limbic sympto-
matology, there was a marked decrease in relative perfusion of the vermis in
the individuals with the abuse history. This is indicative of a functional
impairment in the activity of the cerebellar vermis. The vermis is known to
play an important role in modulating limbic irritability, and vermal stimula-
tion is highly effective in suppressing limbic seizure activity [86–89].

Cerebral cortex
The neocortex as a whole matures slowly through cyclic processes of
reorganization [90]. Delayed myelination of the corpus callosum enables the
two hemispheres to develop relatively independently. Language and motor
lateralization is largely established before 5 years of age [91] and emerges
through a multistage process that begins in utero [92–94]. During the first
few postnatal months, the right hemisphere develops more rapidly than
the left, with more advanced dendritic outgrowth [95,96]. However, by
5–6 months of age, dendritic growth in the left hemisphere surpasses that
in the right and continues at a rapid pace for the next 2 years. From 3 to
6 years of age, the right hemisphere accelerates in its development and helps
provide the prosodic components of language that flower between 5 and 6
years of age. Right hemisphere specialization for perception of human faces
emerges between 8 and 13 years of age [97]. The left hemisphere, however,
remains more differentiated. Early experience can exert marked effects on
lateralization in laboratory animals [98–100].
The prefrontal cortex has the most delayed ontogeny of any brain region.
Major projections to the prefrontal cortex scarcely begin to myelinate until
adolescence, and this process continues into the third decade [32,101,102].
The prefrontal cortex also has a relatively high density of glucocorticoid
receptors [103]. Dopamine projections to the prefrontal cortex are specifically
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 407

activated by stress [104–106]. The prefrontal cortex, in turn, exerts inhibitory

effects on all of the major monoamine projections to subcortical regions and
limits their response to stress; it also exerts inhibitory feedback control on the
HPA axis [103,107]. Early in development, stress exerts a widespread effect on
the neuroaxis [108]. As the prefrontal cortex matures, response to stress
becomes more restrictive [108] because of the inhibitory influence of the pre-
frontal cortex on other regions [107]. We have theorized that early stress acti-
vates the developing prefrontal cortex and alters its development. This may
produce precocial maturation of the prefrontal cortex, leading to signs of
early maturation (‘‘parentified child’’), but may arrest the development of
this region, preventing it from reaching full adult capacity [109].
To investigate the effects of childhood trauma on the development of the
left versus right hemisphere, we used a sophisticated quantitative method of
analyzing EEG that provides evidence about the brain’s structure. In con-
trast to conventional EEG, which reveals brain function, the EEG coherence
technique provides information regarding the nature of the brain’s wiring
and circuitry [110,111]. In general, abnormally high levels of EEG coherence
indicate diminished development of elaborate neuronal interconnections in
the underlying cortex that would process and modify the brain signal.
EEG coherence measures indicated that the left cortex of 15 healthy
right-handed pediatric control subjects was more developed than their right
cortex. This was as we expected and consistent with what is known about
the anatomy of the dominant hemisphere. However, the opposite was true
in 15 pediatric psychiatric inpatients with a documented history of abuse.
EEG coherence indicated that their right hemispheres were significantly
more developed than their left, even though they were all right handed
[75,112]. Coherence measures indicated that the right hemisphere of abused
subjects had developed to the same degree as the right hemisphere in the con-
trol subjects. The left hemisphere of the abused subjects lagged substantially
behind the left hemisphere of the healthy control subjects and appeared to
be arrested in its development [75,112].
De Bellis et al. [113] used single voxel proton magnetic resonance spectro-
scopy to measure the relative concentration of N-acetyl aspartate (NAA)
and creatine in the anterior cingulate cortex of 11 children and adolescents
who met DSM-IV criteria for PTSD secondary to maltreatment and 11
healthy matched comparison subjects. They found a significant reduction
in the ratio of NAA to creatinine in the abused subjects with PTSD. NAA
is located primarily within neurons, and reduction of the ratio of NAA to
creatine is a marker of neuronal loss and dysfunction [114]. Hence, these stud-
ies suggest that early maltreatment alters cortical neuronal development.

Functional properties of stress-sensitive brain regions

What are the consequences of stress-related effects on the development of
the hippocampus, amygdala, corpus callosum, cerebral cortex, and cerebellar
408 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

vermis? To better describe the potential effects of stress, a review the functions
of these brain regions follows.

Hippocampus
The hippocampus has long been known to play a critical role in memory
storage and retrieval [115] and is postulated to be a critical locus for the gen-
eration of dissociative states [116]. The hippocampus and parahippocampal
gyrus may also play a dominant role in the pathophysiology of generalized
anxiety and panic disorders [117–119]. These disorders possibly arise from
excess noradrenergic influences on the hippocampus ascending from the
locus coeruleus. Recent research also suggests that the septal area and hippo-
campus are crucial components of the behavioral inhibitory system, which
arrests ongoing behavior when it is environmentally inappropriate [120].
Serotonergic projections from the median raphe nuclei to the hippocampus
presumably play an important role in establishing an individual’s overall
level of behavioral inhibition [120]. Thus, alterations in hippocampal devel-
opment may subserve the anxiogenic, dissociative, amnestic, and disinhibi-
tory aspects of PTSD.

Amygdala
The interconnecting amygdaloid nuclei have been strongly implicated in
fear conditioning and in the control of aggressive, oral, and sexual behaviors
[115]. Episodic dyscontrol and impulsive violence in man may be caused by
irritable foci in the amygdaloid nuclei [115]. It is also likely that this region is
involved in the formation and recollection of emotional memory and in the
learning of nonverbal motor patterns. The amygdala is thought to play a
crucial role in triggering fight-or-flight responses [121]. Excessive amygda-
loid activation has been proposed to play a crucial role in the development
of PTSD [73,122–125].

Temporolimbic seizures
Seizure foci producing partial complex seizures are often localized to lim-
bic structures in the temporal lobe. One of the primary known causes (or
consequences of seizures) is hippocampal sclerosis, which is characterized
by neuronal loss in the dentate nucleus and in the CA1 and CA4 sectors
of the hippocampus. These lesions cause shrinkage of the hippocampus that
can be detected by MRI. Amygdaloid damage has also been observed in a
significant percentage of patients with TLE [126,127]. What are the potential
consequences of partial complex seizures or abnormalities in temporal lobe
electrophysiology? One controversial consequence may be a tendency to-
ward aggressive behavior. EEG abnormalities are frequently present in
patients with episodic violence. For instance, in a study of 130 violent
patients with substantial histories of childhood deprivation, parental psy-
chiatric illness, and family violence, Bach-y-Rita [128] found that 50% of all
patients receiving EEGs showed abnormalities, particularly temporal spikes.
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 409

EEG abnormalities have also been reported to be a significant risk factor

for suicidal ideation or attempts. One of the earliest pioneering studies on
the physiologic determinants of suicide reported a strong positive associa-
tion between paroxysmal EEG disturbances and suicidal ideation, attempts,
and assaultive-destructive behavior [129]. It has also been reported in the
neurological literature that the risk of completed suicide is 4 to 5 times
greater in epileptic than among non-epileptic patients and that this risk may
be 25-fold greater in patients with temporal lobe epilepsy [130,131]. As many
as one third of all epileptic patients have attempted suicide at some point in
their life [132,133]. This risk is far greater for epileptic patients than for
patients with other medical disorders that produce a comparable degree
of handicap or disability [134].

Hemispheric laterality
The two cerebral hemispheres are specialized to a considerable degree in
their information processing abilities. Usually, the left hemisphere is special-
ized for the perception and expression of language and is logical and ana-
lytical. The left hemisphere is also slightly more intricate in its development,
and it usually dominates in a variety of tasks. The right hemisphere appears
to play a pivotal role in the perception and expression of emotion, particu-
larly negative emotion [135–139]. Hemispheric dominance and degree and
direction of lateralized function are controlled by genetic, hormonal, and
experiential factors [100,140–142]. The two hemispheres are connected
through the corpus callosum and the anterior and posterior commissures.
The two hemispheres need to interact closely to ensure optimal function
[143]. Cynader et al. [144] has shown in kittens that the normal bidirectional
flow of information from the right and left hemispheres through the corpus
callosum can be affected by early experience. In extreme circumstances, the
corpus callosum can be so affected that communication becomes entirely
unidirectional. We have hypothesized that early stress strongly affects the
degree of right–left hemispheric integration [78,109,145].
Neurotransmitter systems are lateralized in their innervation patterns in
both rats and humans [146–148]. The degree and direction of these hemi-
spheric differences may have important behavioral consequences. For exam-
ple, we observed that right> left asymmetries in serotonin and dopamine
projections to the amygdala and prefrontal cortex, respectively, were much
more highly correlated with levels of anxiety than with actual transmitter
levels [149]. Early stress alters the development of monamine neurotransmit-
ters and affects their degree of laterality [66,150].

Cerebellar vermis
Although the cerebellum has not generally been regarded as an important
brain region in the maintenance of psychiatric health, this picture is rapidly
410 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

changing with increasing awareness of the critical role of the cerebellum in

attention, language, cognition, and affect [151–155]. Indeed, linguistic and
emotional disruptions appear to be the primary clinical manifestation of
vermal lesions [152]. The terms ‘‘dysmetria of thought’’ [153,156] or ‘‘cogni-
tive dysmetria’’ [157] have been used to characterized defects in the ‘‘speed,
capacity, consistency and appropriateness of mental or cognitive processes’’
[156] accompanying cerebellar damage. Phylogenetic evidence suggests that
expansion of the cerebellar hemispheres during the last million years paral-
lels the dramatic evolutionary increase in the size of the frontal lobes
[79,158]. Although the cerebellum occupies only 10% to 20% of brain
volume, it contains more than half of all neurons in the brain [159].
An enormous convergence of new data suggest that abnormalities in the
cerebellar vermis may be involved in a wide array of psychiatric disorders,
including bipolar and unipolar depression [160–163], schizophrenia [164–
169], autism [170–172], and ADHD [173–175]. The cerebellar vermis exerts
strong modulatory effects on the locus coeruleus, the ventral tegmental area,
and the substantia nigra, which are cell body regions for projection of the
primary norepinephrine and dopamine pathways [176–178].
The cerebellum probably plays a critical role in mediating response to
stress. It has a high density of GC receptors [56,80,81] and CRF recep-
tors [179]. Recent evidence suggests that there are reciprocal connections
between the vermis and certain hypothalamic nuclei [180], which could play
a role regulating circulating glucocorticoid levels. Rilling et al. [181] have
reported a correlation between plasma cortisol concentrations and meta-
bolic activity in the vermis of juvenile rhesus monkeys. The cerebellum not
only modulates the systemic circulation but also profoundly influences
cerebral blood flow and initiates long-term neuroprotection of the brain
from ischemia independent of its effects on blood flow [176]. Stimulation
of the cerebellar fastigial nuclei provokes release of catecholamines from
the adrenal glands [182] and substantially increases plasma levels of vaso-
pressin [183].
Our interest in the cerebellar vermis stems from the work of Harlow
[184,185] on the deleterious effects of maternal separation and early iso-
lation. Mason and Berkson [186] showed that swinging wire primate sur-
rogates greatly diminished the degree of psychopathology (aggression,
self-stimulation) seen in adults raised in isolation. Prescott [187] suggested
that both proprioceptive and vestibular stimulation was protective, and Ber-
man [188] found that lesions of the vermis, which receives major input from
the vestibular system, eliminated aggressive behavior. Heath [189] found
that primates reared in this manner had epileptiform EEG patterns in their
hippocampus and fastigial nuclei, which project from the vermis to the lim-
bic system and modulate seizure susceptibility [87,88,190]. Taken together,
these findings suggest that the vermis is an important region for the main-
tenance of psychiatric health and that it may mediate some of the primary
neurobehavioral consequences of early stress or neglect.
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 411

From neurobiology to symptomatology

In summary, childhood abuse is linked with excess neuronal irritability,
EEG abnormalities, and symptoms suggestive of temporal lobe epilepsy.
It is also associated with diminished development of the left hemisphere
(including the neocortex, hippocampus, and amygdala), reduced size of the
corpus callosum, and attenuated activity in the cerebellar vermis. There is a
close fit between the effects of early maltreatment on brain development and
the array of psychiatric symptoms observed in abused patients.

Depression
Many disorders are associated with childhood abuse; one such disorder is
depression or the heightened risk for developing it. Depression may be a
consequence of reduced activity of the left frontal lobes [191,192]. If so, the
stunted development of the left hemisphere related to abuse could easily
enhance the risk of developing depression. Depression has also been asso-
ciated with hypersecretion of CRF, hypercortisolemia, and diminished feed-
back regulation of cortisol. Heim et al. [193] have hypothesized that early
life stress enhances CRF neuronal activity and sensitizes the anterior pitu-
itary to the effects of subsequent stress exposure. Exposure to frequent non-
specific stress may result in downregulation of CRF receptors, dysregulation
of cortisol rhythms, and emergence of symptoms of depression [194].

PTSD
In a similar manner, early childhood maltreatment can lead to the emer-
gence of PTSD or increase risk of developing PTSD in response to sub-
sequent trauma [195,196]. Enhanced risk may be related to CRF neuronal
overactivity [197]. Subsequent exposure to infrequent specific traumas may
sensitize the CRF receptor system and enhance feedback and the circadian
regulation of cortisol, providing the neuroendocrine underpinnings for
PTSD [194]. Molecular alterations within the amygdala and locus coeruleus
may produce limbic irritability or kindling, induce sympathetic hyperarou-
sal [73], enhance fear or startle reactions [125], augment fight-or-flight res-
ponses [122], and lead to the emergence of intrusive memories [123], which
are other components of PTSD. Furthermore, adverse effects of early stress
on hippocampal development may facilitate the emergence of the dissocia-
tive and amnestic components of PTSD [110].

Attention-deficit/hyperactivity disorder
There also appears to be an association between childhood abuse and
emergence of symptoms of ADHD. Pynoos et al. [198] found a strong asso-
ciation between exposure to childhood trauma (playground sniper attack)
and emergence of new-onset symptoms of ADHD. Putnam [199] also
reported a relatively high prevalence of ADHD symptoms in prepubertal
412 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

children with a history of sexual abuse. We have also found that 30% of chil-
dren with a history of severe abuse meet diagnostic criteria for ADHD,
although they are objectively less hyperactive than children with classic
ADHD [200]. Abuse in very early childhood was particularly likely to be
associated with the emergence of ADHD-like behavior problems; abuse
later in childhood was associated with emergence of depression [200]. Inter-
estingly, a reduction in the size of the cerebellar vermis seems the most reli-
able anatomical finding in ADHD [173–175]. Some studies have also found
an association between reduced size of the middle portions of the corpus
callosum and the emergence of the ADHD-like symptom of impulsivity
[201]. Hence, early abuse may produce brain changes that mimic key aspects
of ADHD.

Borderline personality disorder

Our discoveries that abused patients have diminished right–left hemi-
sphere integration and a smaller corpus callosum suggest an intriguing
model for the emergence of borderline personality disorder [145,202]. With
less well integrated hemispheres, borderline patients may shift rapidly from
a logical and possibly overvaluing left-hemisphere state to a highly negative,
critical, and emotional right hemisphere state. This seems consistent with the
theory that early problems of mother–child interaction undercut the integra-
tion of right and left hemispheric function [142]. Very inconsistent behavior
of a parent (for example, sometimes loving, sometimes abusing) might gen-
erate an irreconcilable mental image in a young child. Instead of reaching an
integrated view, the child would form two diametrically opposite views—
storing the positive view in the left hemisphere and the negative view in the
right. These mental images, and their associated positive and negative world-
views, may remain unintegrated and the hemispheres may remain auto-
nomous as the child grows up. This polarized hemispheric dominance could
cause a person to see significant others as overly positive in one state and as
resoundingly negative in another. Further, limbic electrical irritability may
be responsible for problems with aggression, and abnormal electrical activ-
ity has been associated with increased risk for suicide and self-destructive
behavior [129]. Previous research has suggested a possible relationship
between temporal lobe-limbic system dysfunction and borderline personal-
ity disorder [203–205]. Snyder and Pitts [204] reported that patients with
BPD had a higher incidence of EEG abnormalities (38% abnormal) than
a contrast group of dysthymic patients (13% abnormal). Similarly, Cowdry
et al. [204] found that 41% of BPD patients had a definite sharp wave
abnormality on EEG, compared with only 5% of patients with unipolar
depression (p < 0.005). Self-destructive behavior, mood fluctuations, and
susceptibility to brief psychotic states may also be a consequence of
stress-induced alterations in dopamine and serotonin levels in the amygdala
and nucleus accumbens [67,68].
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 413

Dissociative identity disorder

Dissociative identity disorder may represent a more extreme degree of atten-
uated hemispheric integration. Flor-Henry et al. [206] reported that patients
with dissociative identity disorder had an extreme degree of left hemisphere
activation. We suspect that some personality shifts may be associated with
activation and transition to a right hemisphere dominant mode. Abnormal
hippocampal development may facilitate the generation of dissociative states,
which may be triggered or exacerbated by the presence of TLE [116,207] or
limbic irritability. Coons et al. [208] reported that significant neurological and
EEG abnormalities were ‘‘infrequently observed in patients with MPD.’’
However, 23% of their population had grossly abnormal EEGs with paroxy-
smal spike and sharp waves—between 5 and 10 times the reported incidence
of these abnormalities in other studies of psychiatric patients [209].

Substance abuse
Early stress or maltreatment is an important risk factor for the later
development of substance abuse [210–213]. Recently, we have proposed that
the cerebellar vermis may be a key region linking the effects of early stress
with heightened risk for substance abuse [83]. There are compelling reasons
to hypothesize that the vermis plays a role in modulating the response to
addictive drugs. The vermis, through its fastigial projections to the ventral
tegmental area and locus coeruleus, exerts strong effects on the turnover
of dopamine and norepinephrine in the caudate and nucleus accumbens
[177,214–216]. The vermis receives direct monoamine projections from the
midbrain [216–219] and has dopamine receptors [220,221] and transporters
[222]. The vermis is affected by stimulants, cocaine, and ethanol. Methylphe-
nidate exerts robust effects on blood flow in these regions [83,223]. The puta-
tive antiaddictive agent ibogaine exerts profound effects on the vermis [224].
ADHD is a serious risk factor for the development of substance abuse
[225,226], and the most consistent anatomical finding in ADHD is reduced
vermal size [173,174]. As reported above, we found that repeated childhood
sexual abuse led to a deficit in perfusion of the vermis but that the degree of
vermal perfusion correlated strongly with LSCL-33 scores. We then evalu-
ated a survey of 537 college students to determine whether there was an
association between degree of substance abuse and ratings on the LSCL-
33. We found that LSCL-33 ratings were most strongly associated with
degree of substance use followed by self-report ratings of depression and
anger/irritability. Together, these finding suggest that early traumatic stress
may enhance risk for later substance abuse by fostering limbic irritability
and inadequate vermal development.

Reframing the effects of early stress from an evolutionary perspective

Initially, our view was that early stress evokes a cascade of neurohumeral
and neurotransmitter effects that produce enduring deleterious alterations in
414 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

brain function. In this narrow perspective, we viewed excessive stress simply

as a toxic agent that interfered with the normal smooth orchestrated pro-
gression of brain development, producing a somewhat altered and impaired
brain [1,69,70,75,78,112]. We also postulated that the neuropsychiatric con-
sequences associated with early exposure to early stress were caused by this
form of developmental insult [1,109,145,202]. This point of view has now
been articulated by several other authors [58,60,227–230]. Our initial model
was complex in that it recognized that there were windows of vulnerability
with different brain regions being vulnerable at different times and that the
range of neuropsychiatric abnormalities manifest would depend on the time
of exposure to stress [1,109].
More recently, we have come to re-evaluate and question this initial view
[231]. Our current hypothesis is that the brain is far more complex and adap-
tive than we had believed. The brain is designed to be sculpted and modeled
by experience, and severe stress has often been a routine component of early
experience throughout the history of our species. It seems unlikely that the
changes that we see in brain development brought on by exposure to early
stress are simply forms of damage occurring in a brain unable to cope with
the cascade of stress responses. Rather, we postulate that the developing
brain copes adaptively to exposure to early stress by following this cascade
as part of an alternative developmental pathway. Hence, neurobiological
difference that we and others have observed are natural and selected modi-
fications in brain structure and function triggered by exposure to certain
forms and levels of stress during key periods of development. These modi-
fications in development are designed to adapt the individual to cope with
high levels of stress or deprivation that they may expect to encounter
throughout the rest of their life. In this fashion, the brain selects an alterna-
tive developmental pathway that will best match its wiring and configu-
ration to the environment that, based on early experience, it expects to
survive and reproduce in.
If an individual is born into a malevolent and stress-filled world, it is cru-
cial for his survival and reproductive success to maintain a state of vigilance
and suspiciousness that enables him to readily detect danger. He will need to
have the potential to mobilize an intense fight–flight response and to react
aggressively to challenge without undue hesitation and to produce a robust
stress response to facilitate survival. In this sense, we can reframe all of the
observed changes as adaptations to facilitate survival and reproductive
success. Alterations in the amygdala and limbic irritability may foster
fight–flight responses and aggressive defense. Hippocampal alterations and
changes in CRF receptor density and neuronal activity may foster a more
robust corticosteroid response. Furthermore, hippocampal abnormalities
may facilitate emergence of dissociation as an intrapsychic defense mechan-
ism. Diminished left hemisphere maturation, reduced corpus callosum size,
and attenuated left–right hemisphere integration may markedly augment an
individual’s capacity to rapidly and dramatically shift into an intense angry
 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426 415

aggressive state when threatened with danger or loss. Diminished develop-

ment of the cerebellar vermis may be crucial for the maintenance of this
state of limbic irritability, hyperarousal, and sympathetic activation.
Exposure to early stress produces a life-long increase in levels of vaso-
pressin mRNA and diminished levels of oxytocin mRNA in the hypothal-
amus [39]. Recent research suggests that oxytocin is a critical factor in
affiliative love, maintenance of monogamous relationships, and normal non-
sexual social interactions [232–237]. Vasopressin is a powerful stress hor-
mone that enables us to cope with blood loss or dehydration, whereas
oxytocin produces an anti-stress response [236]. Both hormones may also
function in the regulation of sexual response, with vasopressin generally
enhancing sexual arousal and oxytocin accompanying climax and release
[238]. Theoretically, early neglect or abuse by altering levels of vasopressin
and oxytocin could predispose mammals to suffer from enhanced sexual
arousal, diminished capacity for sexual fulfillment, and deficient commit-
ment to a single partner. This in turn could foster promiscuity, which may
adaptively facilitate reproductive success in times of danger.
On the other hand, these alterations are not optimal for survival and
reproductive success in a more benign environment. As McEwen [229,239]
has recently articulated, there is a severe cost associated with glucocorticoid
and catecholamine stress responses. In the short run, they are essential for
adaptation, homeostasis, and survival (allostasis). Over longer intervals,
they exact a cost (allostatic load) that can accelerate disease processes. In his
view, early childhood abuse and neglect increase allostatic load and lead
individuals into social isolation, hostility, depression, and substance abuse
and foster the emergence of extreme obesity and cardiovascular disease
[229,239].
In contrast, we hypothesize that adequate nurturing and absence of
intense stress permit the mammalian brain to develop in a manner that is
less aggressive and more emotionally stable, social, empathic, monogamous,
and hemispherically integrated. We believe that this enhances the ability of
social animals to build more elaborate social structures and enables humans
to better realize their creative potentials.
In short, we propose that the brain goes through a sensitive period in
postnatal life in which exposure to high levels of stress hormones select for
an alternative pathway of development that occurs through a cascade of
neurobiological effects. We hypothesize that this process is analogous to the
organizing effects of gonadal steroids on the prenatal brain. Normally, the
mammalian brain is programmed to develop as female. Exposure to sex ster-
oids during a sensitive period programs the brain to develop along an alter-
native masculine pathway. We now propose that exposure to significant
stressors during a sensitive developmental period cause the brain to develop
along a stress-responsive pathway. Furthermore, we hypothesize that
exposure to corticosteroids is a crucial factor in organizing the brain to
develop in this manner. Seckel et al. [240–242] have also postulated that
416 M.H. Teicher et al. / Psychiatr Clin N Am 25 (2002) 397–426

glucocorticoids exert an organizing effect on development. They proposed

that prenatal exposure to glucocorticoids produces low-birth-weight infants
and exerts an organizing effect on the human fetus to produce an enduring
elevation in corticosteroid levels accompanied by a substantially increased
risk for the development of cardiovascular disease and type-II diabetes. In
our hypothesis, postnatal neglect or maltreatment provokes a cascade of
stress responses that organize the brain to develop along a specific pathway
selected to facilitate reproductive success and survival in a world of depriva-
tion and strife. This pathway, however, is costly because it is associated with
the increased risk of developing serious medical and psychiatric disorders
and is unnecessary and maladaptive in a more benign environment.
In this manner society reaps what it sows in the way that infants and chil-
dren are treated. Efforts to reduce exposure to severe stress early in life may
have far-reaching impacts on medical and psychiatric health and may reduce
aggression, suspicion, and untoward stress in future generations.

Acknowledgments
This work was supported by NIMH grants RO1 MH43743 and
MH53636 (MHT). Carl Anderson was supported by a special supplement
to MH53636.

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