Children who spend their infancy in institutional settings where adequate individual caregiving is unavailable are at increased risk for subsequent impairments in affect regulation and behavioral inhibition, which, in turn, contribute to an addictive diathesis. The neuropeptides oxytocin(Drug information on oxytocin) and arginine vasopressin(Drug information on vasopressin) are associated with social bonding, stress regulation, and emotional reactivity. Adopted children who had resided in orphanages for an average of 16.6 months (range, 7 to 42 months) immediately after birth had lower levels of arginine vasopressin than children reared in families. Oxytocin levels of children with families increased after physical contact with their mothers; in contrast, children in the orphanage did not show this response.65 These findings suggest that a deficiency of maternal care during infancy disrupts the normal development of the oxytocin and arginine vasopressin systems, thereby interfering with the development of both affect regulation and social relationships.
In a separate orphanage study, children who were adopted from deprived institutional settings before age 43 months were found to display high degrees of inattention and overactivity at 6 and 11 years of age. They were found also to demonstrate deficits in executive functions of planning, inhibition, set-shifting, working memory, generativity, and action monitoring, which were most severe in children who had experienced more than 6 months of institutional maternal deprivation.66,67 Similarly, controlled preclinical studies have found deficient infant caregiving to be associated with intensified reactivity to acute stressors, increased anxiety-like and depression-like behaviors, decreased social interaction, and increased impulsive behavior.56,68-72 While deficient infant caregiving has been correlated with a broad range of neurobiological abnormalities, the most widely reported are hypersensitivity of the HPA and noradrenergic stress response systems.70-74
A large body of research reports strong associations between adverse childhood experiences and subsequent development of substance use disorders. A study of female monozygotic twins who were discordant for childhood sexual abuse reported that the twin who had been exposed to sexual abuse had a substantially increased risk for alcohol(Drug information on alcohol)ism and other drug addictions.75 A prospective study followed substantiated cases of child abuse and neglect (and demographically matched controls) into young adulthood, and found support for the hypothesis that childhood victimization plays a causal role in the development of alcohol abuse symptoms.76
Similar associations between a range of childhood adversities, especially sexual abuse, and bulimia or other problems with eating or weight have been documented as well.77 However, these associations are less specific than they seem to be. Adverse childhood experiences often coexist and are interrelated,78,79 and abuse of all types is more likely to occur in disturbed families.80 Moreover, childhood sexual abuse appears to increase the risk of a number of psychiatric disorders, rather than being selectively associated with any particular disorder.81,82
Children who have been sexually or physically abused manifest abnormal baseline and stressor-responsive cortisol levels (either abnormally elevated or abnormally flat). Childhood abuse may initially sensitize the stress response system, thus rendering persons who were abused during childhood particularly vulnerable to stress and increasing their risk for stress-related disorders. This vulnerability may result in hypersecretion of corticotropin-releasing hormone whenever they are stressed. A lack of feedback inhibition may also increase the discharge of central corticotropin-releasing hormone.65
Stress and disorders that are related to chronic stress tend to increase dendritic atrophy, accelerate neuronal degeneration, and subvert neuronal regeneration in the hippocampus and hippocampal and prefrontal cortex.83-85 Mediating factors may include chronically elevated levels of glucocorticoid, decreased expression of brain-derived neurotrophic factor, stunted sprouting of serotonergic axons from insufficient availability of brain-derived neurotrophic factor, glial cell loss, and decreased arborization and density of noradrenergic axons.86 In the developing brain, elevated levels of catecholamines and cortisol may lead to structural deviations or deficits through accelerated loss of neurons, delays in myelination, abnormalities in developmentally appropriate synaptic pruning, and inhibition of neurogenesis.87 Sustained glucocorticoid exposure truncates and impairs neurogenesis in the hippocampal and prefrontal cortex.88-90 Reduced baseline and hyporesponsive cortisol levels also can cause neuronal damage.
Together, these processes feed the downward spiral by potentiating hippocampal and cortical atrophy. Neuronal degeneration in the hippocampus and the prefrontal cortex diminishes the capacity of these regions to modulate or inhibit amygdalar stress or fear pathways and the HPA axis, and also undermines hippocampal negative feedback control over cortisol release. Evidence of neuronal loss in the anterior cingulate cortex has been reported in children, adolescents, and nonhuman primates with histories of adverse experiences early in life.91 In addition, adult survivors of early abuse have been found to have changes in hippocampal structure and function.92 Thus, these stress-induced processes may lead to compromised executive function, impaired affect regulation, and a greater incidence of impulsive behaviors.