Michael D. De Bellis

Developmental traumatology part II : Brain development

Abstract Background: Previous investigations suggest that maltreated children with a diagnosis of posttraumatic stress disorder (PTSD) evidence alterations of biological stress systems. Increased levels of catecholaminergic neurotransmitters and steroid hormones during traumatic experiences in childhood could conceivably adversely affect brain development. Methods: In this study, 44 maltreated children and adolescents with PTSD and 61 matched controls underwent comprehensive psychiatric and neuropsychological assessments and an anatomical magnetic resonance imaging (MRI) brain scan. Results: PTSD subjects had smaller intracranial and cerebral volumes than matched controls. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller; while right, left, and total lateral ventricles were proportionally larger than controls, after adjustment for intracranial volume. Brain volume robustly and positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Symptoms of intrusive thoughts, avoidance, hyperarousal or dissociation correlated positively with ventricular volume, and negatively with brain volume and total corpus callosum and regional measures. Significant gender by diagnosis effect revealed greater corpus callosum area reduction in maltreated males with PTSD and a trend for greater cerebral volume reduction than maltreated females with PTSD. The predicted decrease in hippocampal volume seen in adult PTSD was not seen in these subjects. Conclusions: These data suggest that the overwhelming stress of maltreatment experiences in childhood is associated with adverse brain development.

Developmental traumatology part I: biological stress systems ∗

Abstract Background: This investigation examined the relationship between trauma, psychiatric symptoms and urinary free cortisol (UFC) and catecholamine (epinephrine [EPI], norepinephrine [NE], dopamine [DA]) excretion in prepubertal children with posttraumatic stress disorder (PTSD) secondary to past child maltreatment experiences (n = 18), compared to non-traumatized children with overanxious disorder (OAD) (n = 10) and healthy controls (n = 24). Methods: Subjects underwent comprehensive psychiatric and clinical assessments and 24 hour urine collection for measurements of UFC and urinary catecholamine excretion. Biological and clinical measures were compared using analyses of variance. Results: Maltreated subjects with PTSD excreted significantly greater concentrations of urinary DA and NE over 24 hours than OAD and control subjects and greater concentrations of 24 hour UFC than control subjects. Post hoc analysis revealed that maltreated subjects with PTSD excreted significantly greater concentrations of urinary EPI than OAD subjects. Childhood PTSD was associated with greater co-morbid psychopathology including depressive and dissociative symptoms, lower global assessment of functioning, and increased incidents of lifetime suicidal ideation and attempts. Urinary catecholamine and UFC concentrations showed positive correlations with duration of the PTSD trauma and severity of PTSD symptoms. Conclusions: These data suggest that maltreatment experiences are associated with alterations of biological stress systems in maltreated children with PTSD. An improved psychobiological understanding of trauma in childhood may eventually lead to better treatments of childhood PTSD.

Developmental traumatology: the psychobiological development of maltreated children and its implications for research, treatment, and policy.

In this review, a developmental traumatology model of child maltreatment and the risk for the intergenerational cycle of abuse and neglect using a mental health or posttraumatic stress model was described. Published data were reviewed that support the hypothesis that the psychobiological sequelae of child maltreatment may be regarded as an environmentally induced complex developmental disorder. Data to support this view, including the descriptions of both psychobiological and brain maturation studies in maltreatment research, emphasizing the similarities and differences between children, adolescents, and adults, were reviewed. Many suggestions for important future psychobiological and brain maturation research investigations as well as public policy ideas were offered.

Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study

BACKGROUND Previous investigations suggest that maltreated children evidence alterations of chemical mediators of stress and adverse brain development. Previous anatomical magnetic resonance imaging (MRI) brain studies have not controlled for socioeconomic status. METHODS In this study, 28 psychotropic naïve children and adolescents with maltreatment-related posttraumatic stress disorder (PTSD) and 66 sociodemographically similar healthy control subjects underwent comprehensive clinical assessments and anatomical MRI brain scans. RESULTS Compared with control subjects, subjects with PTSD had smaller intracranial, cerebral, and prefrontal cortex, prefrontal cortical white matter, and right temporal lobe volumes and areas of the corpus callosum and its subregions (2, 4, 5, 6, and 7), and larger frontal lobe cerebrospinal fluid (CSF) volumes than control subjects. The total midsagittal area of corpus callosum and middle and posterior regions remained smaller in subjects with PTSD, whereas right, left, and total lateral ventricles and frontal lobe CSF were proportionally larger than in control subjects, after adjustment for cerebral volume. Brain volumes positively correlated with age of onset of PTSD trauma and negatively correlated with duration of abuse. Significant gender x group effect demonstrated greater lateral ventricular volume increases in maltreated male subjects with PTSD than maltreated female subjects with PTSD. No hippocampal differences were seen. CONCLUSIONS These data provide further evidence to suggest that maltreatment-related PTSD is associated with adverse brain development. These data also suggest that male children may be more vulnerable to these effects.

The Psychobiology of Neglect

Child neglect, the most prevalent form of child maltreatment, is associated with adverse psychological and educational outcomes. It is hypothesized that these outcomes may be caused by adverse brain development. However, there are very few published cross-sectional studies and no prospective studies that examine the neurodevelopmental consequences of neglect. In this article, the author comprehensively outlines the issues involved in the psychobiological research of child neglect. Pre-clinical and clinical studies will be reviewed. Throughout the article, suggestions for future research opportunities and novel ways to address methodological difficulties inherent in this field of study are offered. The results of recent neuroimaging studies of maltreated children may provide a basis for understanding the early effects of neglect on childhood brain development. The author is comprehensively examining these issues as part of the Federal Child Neglect Consortium.Child neglect, the most prevalent form of child maltreatment, is associated with adverse psychological and educational outcomes. It is hypothesized that these outcomes may be caused by adverse brain development. However, there are very few published cross-sectional studies and no prospective studies that examine the neurodevelopmental consequences of neglect. In this article, the author comprehensively outlines the issues involved in the psychobiological research of child neglect. Pre-clinical and clinical studies will be reviewed. Throughout the article, suggestions for future research opportunities and novel ways to address methodological difficulties inherent in this field of study are offered. The results of recent neuroimaging studies of maltreated children may provide a basis for understanding the early effects of neglect on childhood brain development. The author is comprehensively examining these issues as part of the Federal Child Neglect Consortium.

Developmental traumatology: a contributory mechanism for alcohol and substance use disorders

Early childhood traumatic experiences, such as childhood maltreatment, are associated with an enhanced risk of adolescent and adult alcohol and substance use disorders (defined as DSM-IV alcohol or substance abuse or dependence). Maltreated children and adolescents manifest dysregulation of major biological stress response systems including adverse influences on brain development. Dysregulation of biological stress response systems may lead to an enhanced vulnerability for psychopathology, particularly posttraumatic stress disorder (PTSD) and depression. These negative affect disorders may put a child at increased risk for adolescent or young adult onset alcohol or substance use disorders. Thus, studies in developmental traumatology may prove to be critical in the effort to attempt to link the neurobiology of maltreatment-related PTSD with the neurobiology of alcohol and substance use disorders and in developing early strategies for the prevention of adolescent and adult alcohol and substance use disorders.

A pilot longitudinal study of hippocampal volumes in pediatric maltreatment-related posttraumatic stress disorder

BACKGROUND Adult posttraumatic stress disorder (PTSD) is associated with decreased hippocampal volumes; however, decreased hippocampal volumes were not seen in pediatric maltreatment-related PTSD. We examined hippocampal volumes longitudinally to determine if a history of childhood traumatic stress alters hippocampal growth during puberty. METHODS Magnetic resonance imaging was used to measure temporal lobes, amygdala, and hippocampal volumes in nine prepubertal maltreated subjects with pediatric maltreatment-related PTSD and nine sociodemographically matched healthy nonmaltreated yoked control subjects at baseline and after at least 2 years follow-up (during the later stages of pubertal development) using identical equipment and measurement methodology. RESULTS Temporal lobe, amygdala and hippocampal volumes did not differ between groups at baseline, follow-up, or across time. CONCLUSIONS Whereas these data are from a small sample, the results do not support hippocampal changes in pediatric maltreatment-related PTSD.

A pilot study of amygdala volumes in pediatric generalized anxiety disorder

BACKGROUND The neurodevelopment of childhood anxiety disorders is not well understood. Basic research has implicated the amygdala and circuits related to these nuclei as being central to several aspects of fear and fear-related behaviors in animals. METHODS Magnetic resonance imaging was used to measure amygdala volumes and comparison brain regions in 12 child and adolescent subjects with generalized anxiety disorder and 24 comparison subjects. Groups were matched on age, sex, height, and handedness and were also similar on measures of weight, socioeconomic status, and full scale IQ. RESULTS Right and total amygdala volumes were significantly larger in generalized anxiety disorder subjects. Intracranial, cerebral, cerebral gray and white matter, temporal lobe, hippocampal, and basal ganglia volumes and measures of the midsagittal area of the corpus callosum did not differ between groups. CONCLUSIONS Although these data are preliminary and from a small sample, the results are consistent with a line of thinking that alterations in the structure and function of the amygdala may be associated with pediatric generalized anxiety disorder.

Pituitary volumes in pediatric maltreatment-related posttraumatic stress disorder.

BACKGROUND The results of previous studies suggest structural brain differences in pediatric maltreatment-related posttraumatic stress disorder (PTSD) However, posterior fossa volumes were not examined, despite the consensus that the cerebellum is important in emotional and cognitive development. We investigated the relationship between structural volumes of the cerebellum hemispheres, vermis, brainstem, and clinical variables in pediatric maltreatment-related PTSD. METHODS Fifty-eight psychotropic-naïve maltreated children and adolescents with DSM-IV PTSD were compared with two groups of pediatric subjects who had no DSM-IV criteria A trauma histories: 1) 13 with pediatric generalized anxiety disorder, and 2) 98 healthy non-abused children and adolescents. Subjects underwent a comprehensive psychiatric assessment and an anatomical magnetic resonance image brain scan. RESULTS Unadjusted means of the left, right, and total cerebellum were smaller in the PTSD group. The group differences remained significant in the left cerebellum, right cerebellum, and total cerebellum in the analyses adjusted for cerebral volume, sociodemographic, and IQ variables. Cerebellar volumes positively correlated with age of onset of the trauma that lead to PTSD and negatively correlated with the duration of the trauma that lead to PTSD. Cerebellar volumes were larger in boys versus girls, but there was no group x gender interaction. There were significant positive correlations between IQ measures and volumetric variables. CONCLUSIONS The results support cerebellar volume differences in maltreated children and adolescents with PTSD. Further studies are warranted.

Urinary Catecholamine Excretion in Sexually Abused Girls

OBJECTIVE The objective of this study was to examine urinary catecholamine excretion in a self-selected sample of sexually abused and demographically matched control girls recruited from a prospective, longitudinal study. METHOD Twenty-four--hour urinary catecholamine and metabolite concentrations of epinephrine, norepinephrine, dopamine, 3-methoxy-4-hydroxyphenylglycol, metanephrine, normetanephrine, vanillylmandelic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in 12 sexually abused and 9 control girls, aged 8 to 15 years. Psychiatric profiles also were obtained. RESULTS The abused subjects excreted significantly greater amounts of metanephrine, vanillylmandelic acid, homovanillic acid, and total catecholamine synthesis as measured by the sum of epinephrine, norepinephrine, dopamine, and their metabolites compared to values from control subjects. When the means of all significant biochemical measures were adjusted by the covariate effect of height, only homovanillic acid and group interaction remained significant. There were positive trends toward significantly higher urinary excretion of metanephrine, vanillylmandelic acid, and total catecholamine synthesis. Sexually abused girls also had a greater incidence of suicidal ideation, suicide attempts, and dysthymia than control girls. CONCLUSIONS These findings support the idea that sexually abused girls show evidence of higher catecholamine functional activity compared with controls. The clinical significance of these findings in their similarity to the psychobiology of both post-traumatic stress disorder and major depressive disorder. Results from this pilot study may be of value in understanding the mechanisms of depressive and anxiety disorders and in the clinical treatment of maltreated children.