This is an Academy version of a journal article originally appearing in Child and Adolescent Psychiatric Clinics of North America.

Official citation: Perry, BD, Pollard, R Homeostasis, Stress, Trauma and Adaptation- A Neurodevelopmental View of Childhood Trauma.  Child and Adolescent Psychiatric Clinics of North America, 7; 1:33-51, 1998.

INTRODUCTION

All life is dynamic. From birth, indeed prior to birth, each of us is bathed in a continuous stream of experience. Through this flow of time, our complex physiology maintains a balancing act, ever changing to maintain some ‘stability’ --- some equilibrium --- some homeostasis. To survive and flourish, we must sense, process, store and respond to elements of our ever-changing environment. The brain is the primary organ responsible for these tasks. By internalizing and storing elements of the unique sequence and collection of our individual experiences, the brain forces us to become reflections of our personal histories. These histories may be filled with consistent, predictable, nurturing and enriching experiences or marred by chaotic, threatening and traumatic experiences. The nature, pattern, and timing of these experiences influence our subsequent functioning. It is from this catalogue of life events that our brain shapes our perceptions and reactions as we move, feel, and think - laugh, love and cry – remember, create or hate.

This chapter will discuss the impact of traumatic experiences on the development and functioning of children as viewed through the lens of developmental neurobiology. This focus on the neurobiology of stress response patterns may provide some insight for those seeking to understand the neuropsychiatric problems resulting from childhood trauma. The recurring theme in a neurodevelopmental view is the remarkable malleability of the developing brain. The brain’s exquisite sensitivity to experience in early childhood allows traumatic experiences during infancy and childhood to impact all future emotional, behavioral, cognitive, social and physiological functioning.

BACKGROUND: TRAUMA AND CHILDREN

It is the rare child that escapes childhood without some cruelty, threat, pain or loss. And far too many children experience more severe chronic or traumatic stress. Millions of children each year experience discreet traumatic events ---natural disasters (64), physical abuse (73;70), sexual assault (17;55) and a host of other specific terrorizing experiences (6;29). Millions of other children live in the traumatizing maelstrom of domestic or community violence (47;93;94;100). These experiences wound and scar the vulnerable, developing child, often resulting in impairments severe and chronic enough to be labeled neuropsychiatric disorders (e.g., reactive attachment disorder, post-traumatic stress disorder, dissociative disorder). Conservative estimates suggest that more than 8 million children, at any given time, are suffering from a trauma-related neuropsychiatric disorder, and that millions more suffer sub-clinical but serious problems (77). The cost to individuals and society by any measure – economic or human - is high.

NEUROPSYCHIATRIC DISORDERS AND CHILDHOOD TRAUMA

The best-characterized neuropsychiatric problems following childhood trauma are posttraumatic stress disorders (75;87). The landmark studies of Terr (103) started the ‘modern’ era of interest in the psychological sequelae of childhood trauma. Over the last twenty years, lagging behind a similar re-discovery of adult PTSD, various important aspects of the phenomenology of childhood PTSD have been studied (30;76;83;88;92;102). Terr has described two broad categories of PTSD in children, differentiating between the effects of chronic, pervasive trauma versus discreet, encapsulated traumatic events(102). This distinction is a good start but better phenomenology is required to understand the various neuropsychiatric syndromes related to childhood trauma (29;30;40;76;83;92).

Children respond to, and are impacted by, traumatic experiences in a host of different ways, and in ways different from adults. Independent of the direct effects of the trauma, the capacity of traumatic experiences to disrupt and interfere with emotional, behavioral, cognitive, social and physical development leads to important secondary and tertiary effects on the child. The current DSM IV diagnostic labels do not capture the diversity of adaptive and maladaptive syndromes that appear to be related to early life traumatic experiences. Among the co-morbid neuropsychiatric diagnoses associated with childhood trauma are major depression, attention deficit disorder with hyperactivity, dissociative disorder, and, following severe early life neglect and trauma, various developmental disorders. While PTSD is not the only, nor an inevitable, outcome of trauma during childhood, post-traumatic hyperarousal or dissociative-like symptoms often co-exist with these other disorders (7;54;87;95). Furthermore, severe early trauma appears to be an expresser of underlying constitutional or genetic vulnerability and maybe a primary etiologic factor in the development of a broad range of disorders later in life (15;71;76).

Initial progress in the area of childhood PTSD was made by comparison with findings or conceptual views derived from adult populations, especially male combat veterans (75;84). These comparisons, once useful, are now very limiting. They leave key questions unasked. What explains the different responses to, and effects of, the same traumatic event on children of different ages? By what mechanisms do traumatic events influence development? What makes an experience traumatic? Why do children of same age react differently to the same traumatic event? Where does ‘resilience’ come from - or vulnerability? Are the effects of trauma in childhood reversible? Advances in understanding childhood trauma require conceptual approaches and research that recognize the unique and distinctive properties of childhood. One such approach uses the core principles of neurodevelopment to frame these issues.

A NEURODEVELOPMENTAL VIEW OF CHILDHOOD TRAUMA

The functional capabilities of the mature brain develop throughout life, but the vast majority of the critical structural and functional organization takes place in childhood. Indeed, by the age of three the brain has reached 90 % of adult size, while the body is still only about 18 % of adult size (96). By shaping the developing brain, experiences of childhood define the adult. This occurs because neurodevelopment is characterized by (1) sequential development and ‘sensitivity’ (from the brainstem to the cortex) and (2) ‘use-dependent’ organization (74;81). The mature organization and functional capabilities of brain reflect aspects of the quantity, quality and pattern of the somato-sensory experiences of the first years of life (12;37;59;16;74;83;97;77). The sequential and use-dependent properties of brain development result in an amazing adaptive malleability, ensuring that, within its specific genetic potential, an individual’s brain develops capabilities suited for the ‘type’ of environment he or she is raised in (83). Simply stated, children reflect the world in which they are raised.

Equilibrium, Stress and Trauma

All living organisms have mechanisms to sense and respond to changes in their environments. These environments – external as ‘sensed’ by our five senses and internal as ‘sensed’ by a set of specialized neurons throughout the body (e.g., glucose or sodium sensitive neurons) – are always changing. Our physiology and neurophysiology are characterized by a continuous, dynamic process of modulation, regulation, compensation, activation – all designed to keep our body’s systems in some state of equilibrium or homeostasis. Each of our many complex physiological systems has a rhythm of activity that regulates key functions; when blood sugar falls below a certain level, a set of compensatory physiological actions are activated. When tissue oxygen is low from exertion, when an individual is dehydrated, sleepy or threatened by a predator, still other regulating activities will be turned on to respond to the specific need. For each of these systems there are ‘basal’ or homeostatic patterns of activity within which the majority of environmental challenges can be sustained.

When there are dramatic, rapid, unpredictable, novel or threatening changes in the environment, however, special ‘stress’-response mechanisms are activated. These brain-mediated responses recruit a set of central and peripheral nervous system, neuroendocrine and immune responses that promote adaptive ‘survival’ functions and, later, a return to equilibrium or homeostatic patterns. Events that disrupt homeostasis are, by definition, stressful. If this stress is severe, unpredictable, prolonged or chronic, the compensatory mechanisms can become over-activated, or fatigued and incapable of restoring the previous state of equilibrium or homeostasis. The physiological system re-organizes its ‘basal’ patterns of equilibrium. An event is ‘traumatic’ if it overwhelms the organism, dramatically and negatively disrupting homeostasis. In a very real sense, trauma throws the organism ‘off balance’, and creates a persisting set of compensatory responses which create a new, but less functionally flexible state of equilibrium. This new, trauma-induced homeostasis is more energy consuming and maladaptive than the previous state. By inducing this "expensive" homeostasis and compromising full functional capability, trauma robs the organism. It has survived the traumatic experience, but at a cost.

Homeostasis and Memory

In this regard, the human organism is no different from others. While exquisitely complex, the core framework of the human brain is designed to sense and respond to the changing environment to promote our individual, and collective, survival. At the heart of our survival neurobiology is the capacity to make and store internal representations of the external world – memory (78). The ability of the brain to create memories is due to the capacity of neurons and neural systems to change from one ‘homeostatic’ state to another. In response to a set of stimuli-induced (e.g., sensations) alterations in activity, neurons undergo molecular changes which reflect this activity (35;52;53). In a very real sense, unless the homeostatic dynamic of a neural system is altered by "use", it will not change – it will not make internal representations of the experience – it will not make memories. Neurons and neural systems change in a "use-dependent" fashion (25). Therefore, when neural systems that have their homeostatic patterns of activation influenced by new or extreme patterns corresponding to new or extreme environmental situations, they will change their molecular neurophysiology, creating ‘memories’ (78).

This has important implications for understanding how we ‘create’ memories of traumatic experiences. For adults, most experiences have only a small component that is ‘new’ or unique. Typically, the majority of places, faces, words, sounds, smells, tastes in any given moment are familiar – the brain has sensed, processed and stored these patterns before. In these situations only some portions of the brain are ‘activated’ and processing outside of their homeostatic range. In the classroom, for example, a lecture may result in cortical activation but will cause little new emotional, motor or arousal activity. The result, hopefully, is new cognitive memories – storing the information from the lecture. Similarly, practicing piano may result in new cerebellar-basal ganglia-motor cortex activity and create ‘motor’ memories but have little effect on emotional or state-regulation areas of the brain.

Trauma, however, induces a total brain response. All parts of the brain will be involved in trying to survive the threat. A traumatic event, by altering activity (and altering the homeostasis) in all parts of the brain – cortex, limbic, midbrain and brainstem – can create different ‘types’ of memory. Altering cortical homeostasis creates cognitive or narrative memory; limbic – emotional memory; midbrain – motor memory and brainstem – physiological state memories (23;62;79;86). These ‘memories’, reflections of the altered equilibrium resulting from a traumatic event, are the heart of trauma-related neuropsychiatric signs and symptoms.

Children are more vulnerable to trauma than adults. Traumatic events modify an adult’s original state of organization or homeostasis but may be the original organizing experience for the child, thereby, determining the ‘foundational’ organization and homeostasis of key neural systems. Experience in adults alters the organized brain, but in infants and children it organizes the developing brain (76;76). This has profound implications for understanding the differences between children and adults experiencing trauma.

The Dynamic Environments of Development

The neurobiological capabilities to sense, store and respond to our environments evolved over millions of years as our pre-hominid and hominid ancestors adapted to the changing demands of their environments. These environments had many components – climate, weather, habitat, predators and prey and, crucial to understanding humans, social structures. Humankind lived for thousands of years in small hunter-forager bands. Our complex social and communication capabilities allowed small, naked, slow and weak individual humans to survive by creating larger, stronger, and more flexible ‘biological’ systems to compete in the harsh natural world inhabited by larger, stronger, faster and naturally-‘armed’ animals (60).

Central elements of our human - then and now - are the dramatic changes in the major environmental challenges associated with the life cycle. The world to which the brain must adapt is dynamic, with dramatic shifts in the major sensory stimuli occurring at key transitional stages of life. Our stream of experience is comprised of shifting environments - new demands, expectations, tasks, capabilities.

It is important to emphasize environments. During the life cycle, the primary internal and external environments are changing. In utero, the sensory cues from the environment include darkness, a constant temperature, an liquid embracing space, the constant vibratory and auditory rhythm from mother’s heartrate. The homeostatic states developing in the environment of the third trimester fetus will be challenged and shifted by birth. The major sensory cues (i.e., environment) of the newborn come from the primary caregiver. Echoing the past, the mother’s embrace, rhythmic rocking and soft humming are familiar and soothing to the newborn. But most sensations and perceptions are new and challenge the rudimentary homeostatic patterns created during intrauterine life. Over time, the newborn’s environment expands, enriches and becomes more complex. More sights and sounds, tastes and touch, all of which push the developing neural systems of the infant, child and adolescent out from a previous set of homeostatic states to find newer and more functionally flexible organizational equilibria. This process – development – can proceed in an optimal fashion when the presentation of new stimuli is safe, nurturing, predictable, repetitive, gradual and attuned to the infant or child’s developmental state. When new experience is chaotic, extreme, or mismatched to developmental stage, development is disrupted. A key to healthy development is matching the nature and pattern of experience to the child’s developmental capability.

What may be a dramatic, rapid or unpredictable shift in environment for the newborn (e.g., a diaper change – which does induce a stress response) may be a familiar, comforting pattern for the one year old and a distressing, humiliating experience for the incontinent 6 year old or 60 year old. It is not surprising, then, that the neurobiological systems and solutions for responding to stress change with the unfolding demands and tasks of various stages during the life cycle (37;38). Infants, for example, can not ‘fight or flee’ (see below). In turn, adults could not survive minor stresses of life with the labile stress-response systems of the newborn. The pattern of stress response preferred at any age is generally matched to demands and tasks of that developmental stage. This means that what may be extremely stressful (or traumatic) at one age may not be at another. A newborn infant that is not touched for two weeks will be severely traumatized while this very same experience will have little impact on an adolescent. As with many other brain-mediated functions, stress response neurobiology and functioning are experience or use-dependent. The individual stress-response style and capacities of any child, then, are related to the process of cataloguing experience during development.

Cataloguing Experience

Throughout life, the brain is sensing, processing and storing patterns of neuronal activation (i.e., making memories) that correspond to various sights, sounds, smells, tastes, movements. Using various modes of memory (e.g., cognitive, emotional, motor) the brain stores these patterns, making associations between the multiple sensory stimuli which co-occur, creating templates of experience against which all future experience is matched (79).

In this regard, the brain is a conservative organ. It does not like to be surprised. All unknown or unfamiliar environmental cues are judged to be ‘threatening’ until proven otherwise. Novel stimuli focus attention, increase arousal and induce an alarm response until they can be proven neutral or safe. New patterns and cues that do not match the stored ‘memories’ of previous experience prime the stress-response systems in the brain (5;26;57;61;63). Once categorized as neutral, safe or threatening, these stored ‘memories’ are added to the catalogue of patterns, cues and associations against which subsequent environmental cues are matched.

What is safe and comfortable becomes so through experience; something in the present moment matches the associated, stored ‘memories’ of previous safe, pleasing or rewarding experiences. In contrast, when the environment, internal or external, matches with stored neuronal patterns associated with a previous threatening experience, the brain’s stress- response systems will be activated. Key signs and symptoms of trauma-related neuropsychiatric disorders result from these memories of ‘fear’ – storing elements of traumatic experience, making associations, generalizing and, later, triggering complex, multi-system responses (i.e., cognitive, emotional, motor, ‘state’) reflecting these ‘memories’. This process of creating memories of fear occurs at multiple levels in the brain’s hierarchical systems.

Processing Environmental Cues of Threat

Sensory information from the external environment (visual, auditory, tactile, olfactory, gustatory) and the internal environment (e.g., blood glucose, arterial pressure, CO2 levels) enters the central nervous system at the level of the brain stem and midbrain (36). As this primary sensory input comes into the brain stem and midbrain, it is matched against previously stored patterns of activation and if unknown, or if associated with previous threat, an initial alarm response begins (8;9). The alarm response begins a wave of neuronal activation in key brainstem and midbrain nuclei which contain neurons utilizing a variety of neurotransmitters (e.g., norepinephrine, dopamine, serotonin), neuromodulators and neuropeptides such as ACTH, corticotrophin releasing factor, vasopressin (11;18). Activation of these key systems results in patterns of neuronal activity that spread from brainstem through midbrain, to thalamic, limbic and cortical areas. At the level of the brainstem and midbrain, there is little subjective perception. It is at the level of the thalamus and limbic areas that specific patterns of neuronal activity result in emotional sensations associated with threat – fear, anxiety, anger (26;86). At the sub-cortical and cortical level, more complex cognitive associations are made, allowing interpretation of the experience. The event can be categorized, contexualized and ‘understood’ within a larger perceptual or cognitive framework (97).

Sensing and perceiving threat must be paired with response to threat if the organism is to survive. At each level of the CNS, just as the afferent input is ‘interpreted’ and matched against previous similar patterns of activation, an efferent arm is initiated. Each level and area of the brain has some ‘role’ in the efferent response to the threat. The brainstem will regulate the autonomic and hypothalamic output, alter arousal, tune out distracting sensory information; the midbrain will regulate elements of motor activity (e.g., startle response); the limbic system will modulate emotional reactivity and signaling (e.g., influence facial expression) and the cortex will interpret the threat and develop a complex "plan". Under ideal circumstances, these multiple responses are integrated and orchestrated to mobilize a host of actions that, hopefully, will be ‘adaptive’, reduce risk and enhance survival. These responses are not always well integrated, however. Within each of the distinct neural systems responding to threat independent responses can occur. The Vietnam vet jumps with an exaggerated startle response after a firecracker despite knowing it is not gunfire – the brainstem-midbrain efferent responses occur before the cortex can contextualize and interpret the sound.

The specific response patterns for any individual or situation depend upon many factors including the nature, duration, severity, and history of exposure to similar threat. Age, of course, is a primary factor in determining how the individual will respond to threat. In infants and children, the higher, more complex parts of the CNS have yet to be organized or fully functional. The infant can still have a fear-induced startle, emotional distress and age-appropriate reactivity in response to a traumatic experience but she can not make a ‘plan’. Nor can the traumatized child easily use words, the currency of the adult world, to describe her terror. Adults often misunderstand the ‘silence’ of the maltreated or traumatized, sometimes so badly that the child is considered ‘resilient’ to trauma. It is a very common adult misperception that children are better at coping with "change" or stress than adults. Despite the apparent ease with which many young children survive trauma, they are much more vulnerable to trauma than adults. Indeed it is increasingly clear that the sensitivity and organization of stress-response neurochemical systems are related to developmental experiences with ‘stress’.

Development of Stress Response Neurobiology

Use-dependent, sequential development: At birth, despite having all of its 100 billion neurons in place, the human brain is not completely organized or functional. Brain-mediated functions depend on the process of making and maintaining complex networks of neurons linked by specialized connections called synapses. During the first six months of life the number of synaptic connections rises dramatically. At eight months of age, the synaptic number and density are higher than they will ever be (89;96). The development and organization of functionally important neuronal networks (systems) is "use-dependent". Those synaptic connections that are used are maintained and strengthened while those that are not are pruned out and lost. In a very concrete sense, the experiences of early childhood create patterns of neuronal activity that become the template neural networks and patterns (homeostasis) against which all future experience will be sensed, processed and internalized.

The brain is comprised of many different systems and areas, each mediated some component of brain function. Not all of these systems and areas organize at the same time. At birth, simple regulatory functions (e.g., respiration, temperature regulation) are required while complex cognitive tasks are not. The brain organizes and neurodevelopment proceeds in a sequential fashion, starting from the lowest, most regulatory regions of the brain (i.e., brainstem) and continuing through to the higher, more complex areas (e.g., cortex). This sequential developmental process is guided by experience. As neural systems develop in a ‘use-dependent’ fashion, it is critical that the specific nature, quantity, and pattern of sensory stimuli present in an infant or young child’s life ‘match’ this sequential development. In order to develop the motor systems (and, thereby, motor capabilities), the child must rock, crawl, walk, run, dance. To organize the limbic areas and ‘develop’ the language of socio-emotional functioning, the child must have consistent, nurturing relationships. To organize cortical areas involved in language and cognition, the infant must be exposed to complex symbolic information (i.e., the infant must be talked to).

Timing of experience is crucial. The child that was emotionally neglected for his first three years and then adopted by a loving, caring and nurturing family will still have problems with attachment, intimacy, social interactions and other functions dependent upon healthy limbic development. Sequential development requires that these ‘optimizing’ experiences take place in the appropriate sequence, matching the developmental age of the child. Furthermore, the healthy development of one region/capability is dependent upon the healthy development of lower brain regions that takes place earlier in the process (83;25).

The stress-response systems develop early in life. The key neurobiological systems that mediate the stress response are located in the brainstem and midbrain. Therefore both intrauterine and early childhood experiences play a major role in determining the sensitivity and final organization of these brainstem mediated stress-response systems. The best detailed characterizations of early manipulation and development of neurobiological systems involved in stress comes from animal research (107). In animal models, very different adult stress-response neurobiology and functioning can be created using different patterns and types of intrauterine or perinatal stress (104). In one model, for example, perinatal stress created ‘anxious’ animals while post-natal, moderate stress created ‘resilient’ animals (105).

In humans, studies have demonstrated the key role of the responsive, predictable caregiver in the development of a healthy stress-response neurobiology (37-39). The infant who has a responsive and nurturing caregiver builds in the neurobiological foundations for a flexible and maximally adaptive stress-response. As this infant matures, if she is allowed to explore her ‘novel’ world and have a ‘stable base’ she can turn to when overwhelmed, this child is developing resilience to future stress and trauma. On the other hand, the child exposed to chaotic or threatening caregiving develops a ‘sensitized’ stress response system that impacts arousal, emotional regulation, behavioral reactivity, and even cardiovascular regulation (74;76). These sensitized children are at risk for stress-induced neuropsychiatric problems later in life (77).

STRESS RESPONSE PATTERNS IN INFANCY AND CHILDHOOD

Human beings respond to stress with altered emotional, behavioral, cognitive, social and physiological functioning. The degree and nature of these responses varies from individual to individual in any single event and across events for any given individual. Stress responses are heterogeneous and graded. Two primary but interactive response patterns, hyperarousal and dissociative, have been described (83). Most individuals use various combinations of these two distinct response patterns during any given traumatic event. The predominant response patterns and combinations of these primary ‘styles’ appear to shift from dissociative to hyperarousal during development. While incompletely characterized in children, these two major response continuums illustrate key principles of the neurodevelopmental perspective on trauma.

Hyperarousal: ‘Fight or Flight’ Responses

The activity in the LC mirrors the degree of arousal (i.e., sleep, calm-alert, alarm-vigilant, fear and terror) related to stress or distress in the environment (internal and external). Fear increases LC and VTN activity, increasing the release of norepinephrine in all of the LC and VTN terminal fields throughout the brain. Further along in the hyperarousal continuum, alarm becomes fear. The LC tunes out non-critical information and mediates hypervigilance. This nucleus regulates the complex interactive process which includes activation of centrally-controlled autonomic nervous system tone, the immune system, the hypothalamic-pituitary-adrenal (HPA) axis with resulting release in adrenocorticotropin and cortisol (33). The sympathetic nervous system is further activated, increasing heart rate, blood pressure, respiratory rate, mobilizing glucose, increasing in muscle tone. All of these actions prepare the body for defense -- to fight with or run away from the potential threat. In the face of continuing threat, a full fight or flight response is activated. This full blown response, ‘fight or flight’, was first described by Cannon (20;21) and has been the most studied, best-characterized stress response pattern in humans.

If a child faced with threat responds with a hyperarousal response, there will be a dramatic increase in LC and VTN activity. The hypothalamic-pituitary-adrenal (HPA) axis is crucial to the orchestration of the peripheral response to threat. Corticotropin releasing hormone (CRH) selectively stimulates and regulates adrenocorticotropin (ACTH) secretions in animals (33). ACTH, once released, in turn stimulates adrenal secretions of glucocorticoids or cortisol which causes a myriad of peripheral adaptive responses, including gluconeogenesis, immune system mobilization, altered cellular metabolism, as well as other responses.

As with central neurobiological systems, stress, distress and trauma alter HPA regulation (i.e., a new homeostasis has been induced by the stress). Abnormalities of the HPA axis have been noted in adults with PTSD (69). Chronic activation of the HPA system in response to stress has negative consequences. The ‘homeostatic’ state associated with chronic HPA activation wears the body out (90;91). Hippocampal damage, impaired glucose utilization and vulnerability to metabolic insults (91) may all result. Preliminary studies in a sample of abused children suggests similar hippocampal/limbic abnormalities (48;101).

Following the acute fear response, the brain has created a set of ‘memories’ from the event. These memories are reactivated when the child is exposed to a specific reminder of the traumatic event (e.g., gunshots, a specific male perpetrator). Furthermore, these memories (i.e., cognitive, emotional, motor, physiological state) can be reactivated when the child simply thinks about or dreams about the event. Unfortunately, one of the amazing strengths of the human brain, the capacity to make associations from the specific to the general, begins to betray the traumatized child. Specific cues from the traumatic event may generalize (e.g., gunshots to loud noises, a specific perpetrator to any strange male). In other words, despite being away from threat and the original trauma, these key parts of the child's brain are reactivated again and again. And the memories of fear are seared into the child’s neurobiology.

This ‘use-dependent’ activation of these areas leads to sensitization. Sensitization of catecholamine (LC/VTN-amygdaloid) systems leads to a cascade of associated functional changes in brain-related functions (106; 56;85). Sensitization of the brain stem and midbrain neurotransmitter systems mediating the hyperarousal response also means the other critical physiological, cognitive, emotional and behavioral functions that are mediated by these systems will become 'sensitized'. As the LC/VTN and its target regions (e.g., amygdaloid nuclei) also mediate a variety of other functions (see above), sensitization of these systems by repetitive re-experiencing of the trauma leads to dysregulation of these functions (5). A traumatized child may, therefore, exhibit motor hyperactivity, anxiety, behavioral impulsivity, sleep problems, tachycardia and hypertension
(76 46;72;81).

This means, of course, that the stress response itself becomes sensitized. Everyday stresses which previously may not have elicited any response are now able to elicit an exaggerated reactivity - these children are hyperreactive and overly 'sensitive'. Simply stated, the child is in a persisting fear ‘state’ (i.e., now a ‘trait’). Furthermore, this means that the child’s new basal homeostatic or equilibrium emotional state will be anxiety. And this child will more easily be threatened or terrorized. Over time, these children exhibit a set of maladaptive emotional, behavioral, cognitive, social and physiological problems rooted in the original adaptive response to a traumatic event.

The few research studies examining catecholamine systems in children following trauma suggest a dysregulated, sensitized stress-response neurobiology. In a pilot study of sexual abused girls, they exhibited greater total catecholamine synthesis as measured by the sum of the urinary concentration of epinephrine, norepinephrine and dopamine when compared with matched controls (27;28). In a group of 60 children with PTSD, altered cardiovascular regulation (e.g., increased resting heartrate) has been demonstrated, suggesting altered autonomic regulation at the level of the brainstem (76;82). In other studies, clonidine, an alpha2 adrenergic receptor partial agonist has been demonstrated to be an effective pharmacotherapeutic agent (76). The presumed therapeutic site of action is the LC. These indirect studies all support the hypotheses of a use-dependent alteration in the brainstem catecholamine systems following childhood trauma.

The Dissociative Continuum

Infants, of course, are not capable of fight or flight. Their threat response patterns are unique and, in the initial stages of distress, are characterized by a precursor form of a hyperarousal response. In these pre-alarm and alarm stages, the infant will use his or her limited behavioral repertoire to attract the attention of a caregiver. These behaviors include changes in facial expression, body movements and, most important, vocalization, i.e., crying. This is a successful adaptive strategy if the caretaker comes to feed, warm, sooth, fight for, or flee with the infant.

Unfortunately, for many infants and children these strategies are not effective. Indeed, millions of children are maltreated if they are fussy, "difficult", or weepy - threatened by the very adults who should be protecting them. In the absence of an appropriate caregiver reaction to the initial alarm outcry, the child will abandon this behavior. Furthermore, if the infant or child has few if any positive responses and negative responses from the caregivers following this, they will abandon this set of adaptations. The converse of use-dependent development occurs – disuse related extinction of a behavior. This defeat response is well-characterized in animal models of stress reactivity and ‘learned helplessness’ (65). This defeat reaction is a common element of the presenting emotional and behavioral phenomenology of many neglected and abused children (22;24;32;65;98;99). Indeed, adults, professional or not, often puzzle over the emotional non-reactivity, passivity and ‘compliance’ of many abused children. All too often this defeat reaction is mistaken for resilience. "Can you believe how easy it is for her to talk about all those horrible things they did to her, and she is so easy to have around, so compliant. What a tough little girl! But I guess kids are just resilient, right ?" Wrong. Children are malleable. Children become resilient if they build in a responsive stress response neurobiology, mirroring their experiences of predictable and nurturing early caregiving.

In the face of persisting threat, and with no adequate response forthcoming from the initial alarm response, the infant or young child will be forced to activate other responses to adapt. If the child is old enough, this may involve moving further along the hyperarousal continuum (the child’s version of ‘fight or flight’); for infants, however, this will involve activation of dissociative adaptations. Dissociation is a broad descriptive term which includes a variety of mental mechanism involved in disengaging from the external world and attending to stimuli in the internal world. This can involve distraction, avoidance, numbing, daydreaming, fugue, fantasy, derealization, depersonalization and, in the extreme, fainting or catonia. In our experiences with young children and infants, the predominant adaptive responses during the trauma are consistent with dissociative mechanisms. Traumatized children use a variety of dissociative techniques. Children report going to a 'different place', assuming persona of heroes or animals, a sense of ‘watching a movie that I was in’ or ‘just floating’ - classic depersonalization and derealization responses. Observers will report these children as numb, robotic, non-reactive, "day dreaming", "acting like he was not there", staring off in a glazed look. The younger the child the more likely there will be primary dissociative adaptations. Immobilization, inescapability or pain will increase the dissociative components of the stress response patterns at any age.

In animals, the ‘defeat’ response is mediated by different neurobiological mechanism than the ‘fight or flight’ response. What little is known about the neurobiology and phenomenology of dissociation appears to most approximate the ‘defeat’ reaction described in animals (14;42;44;65). As with the hyperarousal response, there is brainstem mediated CNS activation which results in increases in circulating epinephrine and associated stress steroids (34;43;45). A major difference in the CNS, however, is that vagal tone increases dramatically, decreasing blood pressure and heart rate (occasionally resulting in fainting) despite increases in circulating epinephrine.

Dopaminergic systems, primarily mesolimbic and mesocortical, play an important role in defeat reaction models in animals (49;51 50 4;41;42). These dopaminergic systems are intimately involved in the ‘reward’ systems, affect modulation (e.g., cocaine-induced euphoria) and, in some cases, are co-localized with endogenous opioids mediating pain and other sensory processing (19). The opioid systems are clearly involved in altering perception of painful stimuli, sense of time, place and ‘reality’. Opioids appear to be major mediators of the ‘defeat’ reaction’s dissociative behaviors (3). Indeed, most opiate agonists can induce dissociative responses in humans.

Little research on the neurobiology of dissociation in children exists. In our preliminary studies, traumatized children with dissociative symptoms demonstrated lower heartrates than comparison traumatized children with hyperarousal symptoms. Cue specific decreases in heartrate were documented using continuous heartrate monitoring. In contrast, cue specific increases in heartrate were seen in the children with persisting hyperarousal symptoms (82). In a recent case series with ten children suffering from severe dissociative symptoms (e.g., fainting, catatonia, bradycardia) naltrexone, an opioid antagonist, improved dissociative symptoms (80). The hypothesized therapeutic site of action is the opioid receptors regulating LC activity (3).

The capacity to dissociate in the midst of terror appears to be a differentially available adaptive response - some people dissociate early in the arousal continuum. Some people dissociate only in the state of complete terror. The determinants of individual differences in the specific stress response to threat have yet to be well characterized. One important observation is a clear gender difference. Females tend to dissociate much more frequently than men. This is likely due to multiple factors, but it is a persistent observation across all ages and cultures. In its most common form, however, the child and adult response to trauma is an admixture of these two primary adaptive patterns. Admixture of hyperarousal with a partial dissociative response confers tremendous adaptive advantages (it is what allows the soldier to fight without panic). This advantage is age-dependent. Little adaptive advantage is conferred to a young child using only a hyperarousal response. Children’s admixture of response preference changes with maturity. The older a child becomes, the more viable is a full blown ‘fight or flight’ response.

Freezing

One of the most common behavioral presentations seen in the combined hyperarousal-dissociation response pattern is ‘freezing’. The teleological adaptive advantage of this is clear. Freezing allows a prey to localize with more accuracy and the lack of movement makes it harder for movement-dependent predators to localize the prey. In the animal kingdom, freezing is a very common predecessor of flight. In some animals such as the opossum, the freezing response is the primary adaptive response to threat. For humans, freezing is only a component of a more complete set of possible responses. It is used, however, in the face of escalating threat, to facilitate a ‘regrouping’. Fear impairs thinking, a human’s best defense. Freezing can allow the escalating anxiety to plateau, and give the person a chance to ‘organize’ and ‘make a plan’.

Children who have been traumatized and have developed a ‘sensitized’ hyperarousal or ‘sensitized’ dissociative pattern will often use this freezing mechanism when they feel anxious. Typically this freezing behavior is labeled oppositional-defiant. The child with a history of maltreatment will feel threatened due to an evocative stimulus which has tapped into their emotional and state memories of previous threat (e.g., a family visit). The child rarely understands why but they are anxious. In this state, they are less capable of processing complex information and are easily overwhelmed. They feel out of control and will cognitively and often, physically, freeze. Caregivers or teachers, unaware of this internal process underway, will ask the child to do something. But the child is ‘frozen’ and refuses. The adult - a teacher, a parent, a counselor - persists. Typically, these directives involve more threat. The adult will say, "If you don't do this, I will...". The nonverbal and verbal character of this 'threat' makes the child feel more anxious, threatened and out of control.

The more anxious the child feels, the quicker the child will move from anxious to threatened, to terrorized. As the child becomes threatened and terrorized, the 'freezing' may escalate into a classic fight or flight becoming aggressive or combative. Conversely, the child may dissolve into a regressed, near-psychotic dissociative state, a condition familiar to too many staff working with maltreated children.

Maladaptive Persistence of Stress Response Patterns and Neuropsychiatric Disorders

The use-dependent nature of neural systems ensures that the changes in homeostasis (i.e., memories) resulting from a traumatic event will be in those neural systems that mediated the stress response during the event. It will be in those neural systems and the functions that they mediate that the altered homeostasis will manifest as dysregulation and dysfunction.

If a child dissociates in response to a severe trauma and stays in that dissociative state for a sufficient period of time, she will alter the homeostasis of the systems mediating the dissociative response (i.e., opioid, dopaminergic, HPA axis). A sensitized neurobiology of dissociation will result and she may develop prominent dissociative-related symptoms (e.g., withdrawal, somatic complaints, dissociation, anxiety, helplessness, dependence) and disorders (e.g., dissociative disorders, somatoform disorder, anxiety disorders, major depression). Children may find artificial ways to facilitate a soothing and reinforcing opioid-mediated dissociation when they suffer from anxiety or other distress. Rocking, head banging, self-mutilation and ‘cutting’ are all distorted self-soothing activities related to the capacity of painful stimuli to activate the brain’s opioid systems.

If a child is traumatized later in life and uses a predominately hyperarousal response, the altered homeostasis will be in different neurochemical systems (i.e., adrenergic, noradrenergic, HPA axis). This child will be vulnerable to developing persisting hyperarousal related symptoms (e.g., hypervigilance, anxiety, impulsivity, sleep problems) and disorders (e.g., PTSD, ADHD, conduct disorder). Both groups are vulnerable to substance abuse and dependence. Using a self-medication perspective, alcohol serves to reduce anxiety in both groups, opiates to induce the soothing dissociation and psychostimulants (e.g., cocaine) to activate dopaminergic ‘reward’ areas in mesolimbic areas for the empty, "defeated" child.

When examining the epidemiological data of neuropsychiatric disorders in children, there is a three to one male to female ratio of childhood psychiatric problems which tends to disappear in adolescence. In early adulthood, this ratio shifts to become two to one female to male. This childhood ratio reflects the nature and pattern of the gender distribution of primary preference in response to stress. Males tend to use hyperarousal responses while females are much more likely to dissociate. In childhood more boys meet the diagnostic criteria for externalizing disorders such as ADHD, conduct disorder, oppositional defiant disorder. In girls there is a higher incidence of internalizing disorders such as depression, anxiety, and dissociative disorders.

Young males typically come to the attention of the clinician because of their externalizing symptoms. There will be reports of aggression, inattentiveness, and noncompliance. Typically these inattentive males are diagnosed with ADHD. Young girls who have been similarly traumatized are not brought to the clinician by the parents (thus the 3:1 male to female ratio?). The maltreated, dissociating girls ‘daydreaming’ in the classroom, are less bothersome to caregivers and teachers than the hyperactive, impulsive and non-compliant boy. Girls are maltreated as much, if not more, than boys. Girl’s brains process trauma with the same principles of neurodevelopment and neurophysiology as boys. Girls are damaged by trauma as much as boys – yet they are much less likely to get our help.

SUMMARY AND FUTURE DIRECTIONS: THERAPEUTIC AND POLICY IMPLICATIONS

All experiences change the brain. But not all experiences have equal ‘impact’ on the brain. Because the brain is developing and organizing at such an explosive rate in the first years of life, experiences during this period have more potential to influence the brain – in positive and negative ways. Traumatic experiences and therapeutic experiences impact the same brain and are limited by the same principles of neurophysiology. Traumatic events disrupt homeostasis in the multiple areas of the brain that are recruited to respond to the threat. Use-dependent internalization of elements of the experience create ‘memories’ which influence future functioning. In order to heal (i.e., alter or modify memories of trauma), therapeutic interventions must activate those portions of the brain that have been altered by the trauma. Understanding the persistence of fear-related emotional, behavioral, cognitive and physiological patterns can lead to focused therapeutic experiences that modify those parts of the brain impacted by trauma.

A neurodevelopmental view of childhood trauma provides novel directions for assessment, intervention and policy. Primary among these is the clear neurobiological rationale for early identification and aggressive, pro-active interventions that will improve our ability to protect, heal, educate and enrich traumatized and neglected children. Future clinical and research efforts in this area must begin to define and use child-specific and developmentally-informed models to guide assessment, intervention, education, therapeutics and policy.

REFERENCES