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A growing body of research has linked childhood experiences of maltreatment with a host of physical conditions that manifest in adulthood. In addition, newer neuroimaging techniques have documented structural changes that occur in the brains of individuals who suffer early maltreatment. This article briefly reviews the literature on these topics and outlines the connection between abuse in childhood and health problems in adulthood.
March 2006 | Back to Table of Contents
Clinical and Health Affairs
Child Maltreatment and Brain Development
By David McCollum, M.D.
Abstract
A growing body of research has linked childhood experiences of maltreatment with a host of physical conditions that manifest in adulthood. In addition, newer neuroimaging techniques have documented structural changes that occur in the brains of individuals who suffer early maltreatment. This article briefly reviews the literature on these topics and outlines the connection between abuse in childhood and health problems in adulthood.
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It has long been observed that some children raised in violent, abusive, or neglectful settings grow up to express violence, anger, depression, or to be engaged in drug use, alcoholism, or criminal activity. The thinking has been that children copy what they see and hear. When anti-social behavior is the norm and when it is reinforced by adults in the environment, children repeat it. During the past 15 years, scientific and clinical research has begun to document that more is at work. Anatomical and functional alterations occur in the brains of children who are exposed to adverse events.1 Research has also shed light on the less obvious link between childhood abuse and lifetime physical and mental health outcomes.2,3 This article reviews some of the research showing the neurobiological, neuroanatomical, and physiological effects of early life stressors and how they might relate to ongoing medical problems later in life.
The Connection between Abuse and Disease
Repeated exposure to adverse or harmful events in childhood has been linked to many adult health consequences. The adverse experiences that have been studied most are sexual abuse, physical abuse, and neglect. Anda et al. identified additional experiences that influence health behavior and outcomes, including mother treated violently, mental illness, substance abuse, incarcerated household member, and parental separation or divorce.4 Because at least 30% of children in this country experience some form of child abuse prior to age 18, we can expect adverse childhood experiences to have a significant impact on the health care system.5
New technologies such as functional MRI, PET, and MRI/T2 relaxometry (T2-RT) have enabled scientists to identify the chemical and structural differences between the central nervous systems of abused and nonabused individuals.6,7 This research shows that many health problems—including panic disorder/post-traumatic stress disorder, chronic fatigue syndrome, fibromyalgia, depression, some auto-immune disorders, suicidal tendencies, abnormal fear responses, preterm labor, chronic pain syndromes, and ovarian dysfunction—can be understood, in some cases, as manifestations of childhood maltreatment.8-13
Brain Development
An infant’s brain is equipped with an overabundance of neurons, synaptic potential, and dendrites. DNA is responsible for early brain development. But after birth, experience helps to determine which neurons will persist, which synapses will develop and become permanent, and which connections will take prominence or be subdued. Myelination, formation of the protective sheath surrounding nerve fibers, continues throughout childhood and, in some areas of the brain, into the third decade of life. This process establishes final, permanent linkages within the brain structures.14
The limbic system is the part of the brain most vulnerable to adverse childhood experiences. The system is made up of the amygdala, hippocampus, cingulate gyrus, thalamus, hypothalamus, and putamen. Related structures include the cerebellar vermis, prefrontal cortex, and visual and parietal cortex. The limbic system is responsible for the generation and control or inhibition of emotions. It is also involved in interpreting facial expressions and evaluating danger, is responsible for the fight-or-flight response to stress, and integrates emotional reactions and connects them with the physical response. Various components are also involved in memory, both implicit and explicit, and in learning (Table).
Brain Sequelae
Stress initiates a series of hormonal responses in the limbic system. The initial response to stress or danger is activation of the hypothalamic-pituitary- adrenal (HPA) axis. This occurs in the locus coeruleus and the sympathetic nervous system, causing a release of the hormones norepinephrine, serotonin, and dopamine. The amygdala reacts to this hormone release and, in turn, stimulates the hypothalamus to release corticotrophin-releasing factor (CRF). CRF, itself, acts as both a hormone, to stimulate adrenocorticotropin hormone (ACTH) secretion, and as a neurotransmitter, affecting areas of the cortex that are involved in executive functioning (eg, motivation, planning, and logic).15 Increasing ACTH secretion then leads to elevated glucocorticoids (cortisol). High levels of glucocorticoids have been shown to negatively affect the hippocampus, resulting in decreased dendritic branching, changes in synaptic terminal structure, and neuronal loss.16 A feedback mechanism in the hypothalamus and the hippocampus normally brings these levels back to their resting state.
If this process occurs repeatedly, CRF and glucocorticoids remain elevated, which eventually causes structural changes in the brain and impedes the feedback mechanism, leading to an imbalance in hormones and dysregulation of the HPA axis.17
Signs of Stress in the Brain
Several studies have shown a measurable reduction in the size of the amygdala, hippocampus (primarily the left side), corpus callosum, and the cerebellar vermis, and an increase in size of the putamen and lateral ventricles in both children and adults who experienced repeated childhood trauma.18-20 These changes are thought to be an effect of elevated glucocorticoid levels inhibiting myelination in these structures.14 Because most areas of the limbic system are high in glucocorticoid receptors, they are susceptible to the effects of early childhood abuse.
Functional changes have also been noted in the anterior cingulate gyrus and the visual and parietal cortex. Elevated resting levels of CRF have been found in the spinal fluid of abuse victims.21 Elevated T3 levels have also been found in patients with a history of childhood abuse.22
Dopamine, which is released during the stress response, stimulates areas of the prefrontal cortex, probably resulting in heightened attention and improved cognitive capacity. Chronic stress, however, appears to cause an overproduction of dopamine, which can result in reduced attention, increased overall vigilance, as well as a diminished capacity to learn new material and increased paranoid and psychotic behavior.23
Serotonin stimulates both anxiogenic and anxiolytic circuits, which create and reduce anxiety. Decreased serotonin levels in the prefrontal cortex have been found as a result of chronic stress. Suicidal behavior, depression, and aggression have been shown to result from low serotonin levels.
Substance P, a neuropeptide found throughout the body that participates in the pain response and inflammation, has been found at much higher levels in the spinal fluid of those with significant abuse history. Studies in rats showed that injecting high levels of substance P in the spinal fluid caused a significantly exaggerated pain response to a noxious stimulus.24
Related Health Problems
The health problems associated with these changes in the brain are significant. According to Anda et al., atrophy of the hippocampus, amygdala, and prefrontal cortex, and the subsequent dysfunction is related to anxiety, panic, depressed affect, hallucinations, and substance abuse. Increased locus coeruleus and norepinephrine activity have been related to tobacco use, alcoholism, illicit drug use, and injectable drug use. Defects in the amygdala and related deficits in oxytocin result in sexual aggression, sexual dissatisfaction, perpetration of intimate partner violence, and impaired pair bonding.4
Anderson et al. used a novel technology called static functional MRI T2 relaxometry (T2-RT) on a population that had experienced childhood sexual trauma and found evidence of significant changes in the cerebellar vermis in abused individuals compared with nonabused individuals.6 The vermis has been shown to play a role in suppressing excitability within the limbic system. The most consistent anatomical finding in children with ADHD is a reduction in the size of the cerebellar vermis. Other studies show similarities in hormonal changes in children with ADHD. Famularo showed a high correlation between traumatic family environments and ADHD comorbidity.25,26
Allsworth showed that dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis, common in people who have been abused, leads to ovarian dysfunction and early menopause.13 This is likely to increase the risk of cardiovascular disease in these women because estrogen is reduced prematurely and, therefore, its protective function is lost earlier, increasing risk for cardiovascular disorders. Another interesting finding is that early stress may lead to premature involution of the thymus gland. Anti-nuclear antibodies, which attack the body’s own tissues instead of foreign toxins and are frequently present in people with systemic lupus erythematosus, also have been found at higher levels in girls who have been sexually abused compared with those who have never experienced abuse.9
The link between fibromyalgia and sexual abuse has been extensively studied.27 Dysregulation of the HPA axis has been found in most patients with fibromyalgia.28 Substance P is found in high levels in this population. Irritable bowel syndrome has also been shown to be correlated with childhood sexual abuse, and higher levels of substance P have been found in the colonic mucosa of individuals who were maltreated as children. Also, increased glucocorticoid has been shown to act on the intra-abdominal adipocytes leading to increased fat storage.4 Findings that memory pathways are adversely affected by exposure to abuse may explain some amnesia, delayed recall of abuse, and dissociative disorders.29 Some authors consider conversion reactions and pseudoseizures a form of dissociative disorder.30
Conclusion
For years, we have ignored the potential influence of childhood traumatic experiences on adult disease, preferring to look for genetic causes of disease and pure biochemical factors without considering experiential influences. Given new evidence that trauma in childhood alters the physiology of the brain, it is time for all physicians to be educated about the full health impact of violence and abuse and be trained to explore these issues as the true etiology of or an underlying potentiating factor that contributes to their patients’ maladies. MM
David McCollum is an emergency physician at Ridgeview Medical Center in Waconia, chair of the AMA National Advisory Council on Violence and Abuse, and president-elect of the Academy on Violence and Abuse.
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