ArticleLiterature Review

McCrory E, De Brito SA, Viding E. Research review: the neurobiology and genetics of maltreatment and adversity. J Child Psychol Psychiatry Allied Disciplines 51: 1079-1095

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Abstract

The neurobiological mechanisms by which childhood maltreatment heightens vulnerability to psychopathology remain poorly understood. It is likely that a complex interaction between environmental experiences (including poor caregiving) and an individual's genetic make-up influence neurobiological development across infancy and childhood, which in turn sets the stage for a child's psychological and emotional development. This review provides a concise synopsis of those studies investigating the neurobiological and genetic factors associated with childhood maltreatment and adversity. We first provide an overview of the neuroendocrine findings, drawing from animal and human studies. These studies indicate an association between early adversity and atypical development of the hypothalamic-pituitary-adrenal (HPA) axis stress response, which can predispose to psychiatric vulnerability in adulthood. We then review the neuroimaging findings of structural and functional brain differences in children and adults who have experienced childhood maltreatment. These studies offer evidence of several structural differences associated with early stress, most notably in the corpus callosum in children and the hippocampus in adults; functional studies have reported atypical activation of several brain regions, including decreased activity of the prefrontal cortex. Next we consider studies that suggest that the effect of environmental adversity may be conditional on an individual's genotype. We also briefly consider the possible role that epigenetic mechanisms might play in mediating the impact of early adversity. Finally we consider several ways in which the neurobiological and genetic research may be relevant to clinical practice and intervention.

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Chapter
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Background: Non-suicidal self-injury (NSSI) is defined as inflicting damage to one’s own body. It begins in adolescence and tends to become chronic. Objectives: Considering the high prevalence and chronicity of NSSI among girls, the present study aimed to investigate the factors affecting the prevalence of NSSI in female adolescents from their perspective. Methods: The participants consisted of 604 female high-school students in Saveh, aged 14 - 17 years (14.29 ± 1.11), who were selected via random cluster sampling from November 2018 to January 2019. They answered six questionnaires, including the Inventory of Statements About Self-injury (ISAS), Ways of Coping questionnaire (WCQ), Child Abuse Self-report scale (CASRS), Family Emotional Involvement and Criticism scale (FEICS), Emotion Reactivity scale (ERS), and Aggression questionnaire (AQ). Data were analyzed using logistic regression analysis. Results: The predictor variables of child abuse, emotion reactivity, perceived parental criticism, family emotional involvement, and problem- and emotion-focused coping styles could successfully distinguish NSSI individuals from those without NSSI (P < 0.05). There were no significant differences between minor and moderate groups. Conclusions: Family emotional support is a protective factor, while criticism, child abuse, and emotion-focused coping style are risk factors for NSSI.
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As a founder of the field of applied developmental psychology, Dr Edward Zigler promoted public policy that translated scientific knowledge into real-world programs to improve the outcomes of high-risk children and families. Many researchers, practitioners, and public policy proponents have sought to carry on his legacy through integration of empirical research, evidence-based prevention and intervention, and advocacy to address a range of challenges facing families with young children. To advance the field of child maltreatment, a multidisciplinary team of investigators from the Universities of Rochester and Minnesota partnered with the Eunice Kennedy Shriver National Institute of Child Health and Human Development to create the T ranslational R esearch that A dapts N ew S cience FOR M altreatment Prevention Center (Transform). Building on state-of-the-art research methodologies and clinical practices, Transform leverages theoretically grounded research and evidence-based interventions to optimize outcomes for individuals across the life span who have experienced, or may be at risk for, maltreatment. Inspired by the work of Dr Zigler, Transform is committed to bridging science and real-world practice. Therefore, in addition to creating new science, Transform's Community Engagement Core provides translational science to a broad audience of investigators, child-serving professionals, and parental and governmental stakeholders. This article describes Transform's purpose, theoretical framework, current activities, and future directions.
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Several studies have shown that child maltreatment is associated with both positive and negative effects on the recognition of facial emotions. Research has provided little evidence of a relation between maltreatment during childhood and young adults’ ability to recognize facial displays of emotion in children, an essential skill for a sensitive parental response. In this study, we examined the consequences of different forms of maltreatment experienced in childhood on emotion recognition during parenthood. Participants included sixty-three mothers of children aged 2 to 5 years. Retrospective self-reports of childhood maltreatment were assessed using the short form of the Childhood Trauma Questionnaire (CTQ). Emotion recognition was measured using a morphed facial emotion identification task of all six basic emotions (anger, disgust, fear, happiness, sadness, and surprise). A Path Analysis via Structural Equation Model revealed that a history of physical abuse is related to a decreased ability to recognize both fear and sadness in children, whereas emotional abuse and sexual abuse are related to a decreased ability to recognize anger in children. In addition, emotional neglect is associated with an increased ability to recognize anger, whereas physical neglect is associated with less accuracy in recognizing happiness in children’s facial emotional expressions. These findings have important clinical implications and expand current understanding of the consequences of childhood maltreatment on parents’ ability to detect children’s needs.
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The ability to provide appropriate responses to infant distress is vital to paternal care, but may be affected by fathers’ experiences of childhood maltreatment. Detrimental effects of childhood maltreatment have been found in the adult brain's white matter fibers, accompanied with impaired emotional and cognitive functioning. In the current study (N = 121), we examined new and expectant fathers’ childhood maltreatment experiences (i.e. emotional and physical abuse and neglect), current behavioral responses (i.e. handgrip force) to infant cry sounds, and white matter integrity using diffusion tensor imaging. First, more exposure to childhood maltreatment was associated with more use of excessive handgrip force in response to infant crying by fathers. Second, the association between experienced childhood maltreatment and white matter integrity was not significant in whole‐brain analyses. Lastly, we found that the association between maltreatment exposure and excessive handgrip force during infant crying was absent in fathers with high tract integrity in the bilateral uncinate fasciculus. These findings possibly point to insufficient behavioral inhibition or emotional dysregulation in fathers who experienced childhood maltreatment, but buffering for this effect in those with larger integrity in brain fibers connecting the amygdala and prefrontal cortex.
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Social emotional learning (SEL) programs are increasingly being implemented in elementary schools to facilitate development of social competencies, decision-making skills, empathy, and emotion regulation and, in effect, prevent poor outcomes such as school failure, conduct problems, and eventual substance abuse. SEL programs are designed to foster these abilities in children with a wide range of behavioral, social, and learning needs in the classroom, including children who are economically disadvantaged. In a previous study of kindergartners residing in a high-poverty community (N = 327 at baseline), we observed significant behavioral improvements in children receiving an SEL program-The PATHS® curriculum (PATHS)-relative to an active control condition within one school year. The present investigation sought to determine whether these improvements were sustained over the course of two school years with intervention and an additional year when intervention was no longer provided. Further, using multilevel models, we examined whether baseline measures of neurocognition and stress physiology-known to be adversely impacted by poverty-moderated heterogeneous outcomes. Finally, a preliminary linear regression analysis explored whether neurocognition and physiological stress reactivity (heart rate variability, HRV) predict change in outcomes postintervention. Results confirmed that students who received PATHS sustained significant behavioral improvements over time. These effects occurred for the full sample, irrespective of putative baseline moderators, suggesting that children in high-risk environments may benefit from SEL interventions irrespective of baseline cognitive functioning as a function of overall substantial need. Of interest is that our exploratory analysis of change from waves three to four after the intervention concluded brought to light possible moderation by baseline physiology. Should subsequent studies confirm this finding, one plausible explanation may be that, when an intervention providing protective effects is withdrawn, children with higher HRV may not be able to regulate physiological stress responses to environmental challenges, leading to an uptick in maladaptive behaviors. In reverse, children with lower HRV-generally associated with poorer emotion regulation-may incur relatively greater gains in behavioral improvement due to lesser sensitivity to the environment, enabling them to continue to accrue benefits. Results are discussed in the context of possible pathways that may be relevant to understanding the special needs of children reared in very low-income, high-stress neighborhoods.
Chapter
Sexual abuse is a serious social issue with adverse psychosocial consequences in the person who is victimized. High prevalence rate of abuse in both children and adults, no matter female or male, indicate that anyone can be a victim of this hazard. The manifestation of mental-health outcomes is diverse in nature and different across individuals and is determined by complex array of factors. This calls for the application of intervention techniques that are well-established by empirical research to be effective among victims of sexual abuse. This chapter is an attempt to discuss treatment methods established as effective and also other methods that are in use, though with limited research literature on its effectiveness or efficacy, for Posttraumatic Stress Disorder (PTSD) and other prominent and debilitating psychological and interpersonal effects of sexual abuse. Further, special issues concerning research and practice as well as future directions are outlined.
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Young children's physiological and emotional regulation depend on supportive caregiving, especially in the context of stress and adversity. Experiences of child maltreatment become biologically embedded by shaping stress physiology. Maternal emotion socialization may have an important influence on children's limbic‐hypothalamic‐pituitary‐adrenal (LHPA) functioning. Grounded in theories of caregiver emotion socialization, a person‐centered latent profile analysis was utilized to identify profiles of maternal emotion socialization among a high risk, low income, and racially diverse group of 248 mothers and their young children (Mage = 4.39 years, SD = 1.10). The majority of the mothers (n = 165) had a history of involvement with the Department of Child Services for substantiated cases of child maltreatment. A latent profile analysis was conducted revealing three emotion socialization profiles: disengaged, engaged, and engaged + supportive. Emotion socialization profile differences in children's diurnal cortisol levels and slope (using area under the curve with respect to ground and increase, respectively) were examined. Children's diurnal cortisol levels were higher, and slopes were flatter, when mothers used more disengaged emotion socialization strategies. Mothers who neglected their children were more likely to fit the disengaged profile than the engaged profile. Implications for the socialization of regulation in children exposed to adversity are discussed.
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Previous research has established associations between early life stress (ELS) and altered pituitary gland volume (PGV) growth during adolescence. The pituitary gland, however, is composed of an anterior and a posterior lobe with distinct histological and neuroendocrinological properties. While the anterior (but not posterior) pituitary gland is directly involved in the hypothalamic-pituitary-adrenal axis (HPAA) stress response, no studies have examined the effects of ELS on anterior PGV (aPGV). The present study investigated whether previously reported associations between ELS and PGV development during adolescence were driven by aPGV versus posterior PGV (pPGV). Ninety-one adolescents (49 males) were included from a longitudinal, community-based adolescent development study investigating risk for psychopathology. ELS (maternal affective behavior, childhood maltreatment, stressful life events) was assessed during early adolescence. Participants underwent two waves of structural magnetic resonance imaging during mid- and late-adolescence, and aPGV and pPGV were manually traced. Regression analyses showed that childhood maltreatment predicted greater aPGV growth in females. This finding was stronger than that previously reported for PGV. No associations were found between ELS and pPGV development. Neither aPGV nor pPGV changes mediated associations between ELS and psychopathology. Results suggest that ELS may accelerate aPGV (but not pPGV) growth throughout adolescence. Investigating the development of aPGV, rather than PGV, represents a novel approach to studying the effects of stress on HPAA functioning.
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Background and purpose: Becoming a parent can be an exciting and also challenging transition, particularly for parents who have experienced significant hurt in their own childhoods, and may be experiencing 'complex trauma.' Aboriginal and Torres Strait Islander (Aboriginal) people also experience historical trauma. While the parenting transition is an important time to offer support for parents, it is essential to ensure that the benefits of identifying parents experiencing complex trauma outweigh any risks (e.g., stigmatization). This paper describes views of predominantly Aboriginal stakeholders regarding (1) the relative importance of domains proposed for complex trauma assessment, and (2) how to conduct these sensitive discussions with Aboriginal parents. Setting and methods: A co-design workshop was held in Alice Springs (Central Australia) as part of an Aboriginal-led community-based participatory action research project. Workshop participants were 57 predominantly Aboriginal stakeholders with expertise in community, clinical, policy and academic settings. Twelve domains of complex trauma-related distress had been identified in existing assessment tools and through community consultation. Using story-telling and strategies to create safety for discussing complex and sensitive issues, and delphi-style methods, stakeholders rated the level of importance of the 12 domains; and discussed why, by whom, where and how experiences of complex trauma should be explored. Main findings: The majority of stakeholders supported the importance of assessing each of the proposed complex trauma domains with Aboriginal parents. However, strong concerns were expressed regarding where, by whom and how this should occur. There was greater emphasis and consistency regarding 'qualities' (e.g., caring), rather than specific 'attributes' (e.g., clinician). Six critical overarching themes emerged: ensuring emotional and cultural safety; establishing relationships and trust; having capacity to respond appropriately and access support; incorporating less direct cultural communication methods (e.g., yarning, dadirri); using strengths-based approaches and offering choices to empower parents; and showing respect, caring and compassion. Conclusion: Assessments to identify Aboriginal parents experiencing complex trauma should only be considered when the prerequisites of safety, trusting relationships, respect, compassion, adequate care, and capacity to respond are assured. Offering choices and cultural and strengths-based approaches are also critical. Without this assurance, there are serious concerns that harms may outweigh any benefits for Aboriginal parents.
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This report describes the protocol for an ongoing project funded by the National Institutes of Health (R01MH108155) that is focused on effects of childhood maltreatment (MALTX) on neurocircuitry changes associated with adolescent major depressive disorder (MDD). Extant clinical and neuroimaging literature on MDD is reviewed, which has relied on heterogeneous samples that do not parse out the unique contribution of MALTX on neurobiological changes in MDD. Employing a 2 × 2 study design (controls with no MALTX or MDD, MALTX only, MDD only, and MDD + MALTX), and based on a cohesive theoretical model that incorporates behavioral, cognitive and neurobiological domains, we describe the multi-modal neuroimaging techniques used to test whether structural and functional alterations in the fronto-limbic and fronto-striatal circuits associated with adolescent MDD are moderated by MALTX. We hypothesize that MDD + MALTX youth will show alterations in the fronto-limbic circuit, with reduced connectivity between the amygdala (AMG) and the prefrontal cortex (PFC), as the AMG is sensitive to stress/threat during development. Participants with MDD will exhibit increased functional connectivity between the AMG and PFC due to self-referential negative emotions. Lastly, MDD + MALTX will only show changes in motivational/anticipatory aspects of the fronto-striatal circuit, and MDD will exhibit changes in motivational and consummatory/outcome aspects of reward-processing. Our goal is to identify distinct neural substrates associated with MDD due to MALTX compared to other causes, as these markers could be used to more effectively predict treatment outcome, index treatment response, and facilitate alternative treatments for adolescents who do not respond well to traditional approaches.
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Emerging evidence suggests that alterations in the development of the gastrointestinal (GI) tract during the early postnatal period can influence brain development and vice-versa. It is increasingly recognized that communication between the GI tract and brain is mainly driven by neural, endocrine, immune, and metabolic mediators, collectively called the gut-brain axis (GBA). Changes in the GBA mediators occur in response to the developmental changes in the body during this period. This review provides an overview of major developmental events in the GI tract and brain in the early postnatal period and their parallel developmental trajectories under physiological conditions. Current knowledge of GBA mediators in context to brain function and behavioral outcomes and their synthesis and metabolism (site, timing, etc.) is discussed. This review also presents hypotheses on the role of the GBA mediators in response to the parallel development of the GI tract and brain in infants.
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Discovering the processes through which early adverse experiences affect children’s nervous-system development, health, and behavior is critically important for developing effective interventions. However, advances in our understanding of these processes have been constrained by conceptualizations that rely on categories of adversity that are overlapping, have vague boundaries, and lack consistent biological evidence. Here, we discuss central problems in understanding the link between early-life adversity and children’s brain development. We conclude by suggesting alternative formulations that hold promise for advancing knowledge about the neurobiological mechanisms through which adversity affects human development.
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The notion of psychological trauma has been liberally used both in clinical literature and general discourse. However, no consensus exists on its exact meaning and definition. Whereas traditionally trauma has been mostly associated with criterion A of acute and posttraumatic stress disorders (PTSDs) as defined in the Diagnostic and Statistical Manual of Mental Disorders, many researchers find this definition too constraining and not accounting for the complexity and many aspects of trauma. This touched off a quest for a broader more accommodating trauma concept, and a dimensional view of trauma with PTSD as its extreme manifestation has been suggested. The dimensional view also has its detractors arguing that “conceptual bracket creep” may undermine the category’s utility. Both categorical and dimensional views mostly rely on trauma’s clinical phenomenology and lack a unified theoretical basis. In an attempt to reconcile this contradiction, a hybrid categorical–dimensional model of trauma based on the general theory of stress has been recently proposed (Krupnik, 2019). Herein, I explore the categorical boundary of the trauma concept, as posited by the model, within the predictive processing framework (PPF). I integrate the PPF view with the theory of stress. In conclusion, I briefly discuss how the proposed model of trauma may guide clinical practice.
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Introduction Even as children experience adversity, they can become resilient adults, in large part due to their social supports as emerging adults. Objective Authors examine constructs of social support applied to the concept of resilience among emerging adults having experienced adverse childhood experiences (ACE). Method Authors conducted a meta-ethnography with six databases between January 1998 and October 2019. Inclusion criteria were as follows: (i) original peer-reviewed qualitative or mixed-method studies, (ii) sampling adults aged 18–35 years, (iii) reporting at least one ACE as defined by the World Health Organization, (iv) focused on resilience, and (v) in English. Data were collected from six electronic databases (MEDLINE, EMBASE, CINAHL, PsychINFO, Web of Science, and Google Scholar). Studies were appraised using the Critical Appraisal Skills Program Qualitative Checklist. Analysis drew on Bourdieu’s constructs of capital following Noblit and Hare’s methods. Results Thirteen studies of 277 emerging adults, aged 18–35 years old (mean 23 years), from six countries, reported resilience as “self-righting” appraisals. These were interdependent of their social supports and within a culturally determined sense of self-reliance. Self-reliance appeared to be a precursor shaping resilience of emerging adults with ACE. Self-reliance may deter self-compassion and, as a self-righting appraisal/capacity, may inhibit accessing social support. Conclusion This review emphasizes the life stage of emerging adulthood regarding the development of self-righting appraisal skills, which, when enabled with reliance, others help to transform ACEs and allow resilience to grow.
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Although the link between childhood maltreatment and violence perpetration in adulthood (i.e., the “cycle of violence”) is well-documented, the neural mechanisms driving these processes remain relatively unknown. The objectives of this study were to investigate whether cortical thickness in adulthood varies as a function of childhood assaultive trauma exposure and whether such neurobiological markers of early trauma relate to the perpetration of aggression across the lifespan. In a sample of 138 ethnically-diverse men and women, whole-brain analysis of the cortical mantle revealed that individuals with exposure to assaultive trauma before age 13 had less cortical thickness in two clusters that survived multiple comparison correction: a region that peaked in the left lateral orbitofrontal cortex (OFC) and a region peaking in the right pericalcarine cortex. Diminished cortical thickness in the left OFC cluster was, in turn, associated with greater physical aggression, and mediation analysis revealed that reductions in cortical thickness in this left prefrontal region partially accounted for the association between exposure to childhood assaultive trauma and lifetime perpetration of aggression in adulthood. Findings extend previous investigations into the morphological correlates of early assaultive trauma by implicating reductions in cortical thickness as a potential mechanism linking early violence exposure to violence perpetration that extends into adulthood.
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Suicide and suicidal behaviors represent a leading cause of morbidity and mortality during adolescence. While several lines of evidence suggest that suicidal behaviors are associated with risky decisions and deficient cognitive control in laboratory tasks in adults, comparatively less is known about adolescents. Here, we systematically reviewed the literature on the association between these neurocognitive variables and adolescent suicidal behaviors. The online search strategy identified 17 neurocognitive studies examining either cognitive control or decision-making processes in adolescents with past suicidal behaviors. Several studies have reported that adolescents with a history of suicidal behaviors present neuropsychological differences in the cognitive control (using Go/NoGo, suicide Stroop Test, continuous performance test, suicide/death Implicit Association Test), and decision-making (Iowa Gambling Task, Cambridge Gambling Task, cost computation, delay discounting, loss aversion tasks) domains. Due to a lack of replication or conflicting findings, our systematic review suggests that no firm conclusion can be drawn as to whether altered decision-making or poor cognitive control contribute to adolescent suicidal behaviors. However, these results collectively suggest that further research is warranted. Limitations included scarcity of longitudinal studies and a lack of homogeneity in study designs, which precluded quantitative analysis. We propose remediating ways to continue neuropsychological investigations of suicide risk in adolescence, which could lead to the identification of novel therapeutic targets and predictive markers, enabling early intervention in suicidal youth.
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This article reviews the evidence for theoretical models postulating that early adversity can set in motion a deleterious developmental cascade, involving changes in hypothalamic-pituitary-adrenal (HPA) axis activity that subsequently affect the development of self-regulation in early childhood. Focusing on the first five years of life, we describe studies showing that experiences of severe deprivation or maltreatment may both lead to a hypoactive HPA axis in children. However, it is too early yet to conclude what effects exposure to adverse conditions such as poverty or family instability have on young children’s HPA axis, with both low and high levels of cortisol having been observed under these circumstances. Both patterns of HPA axis dysregulation have been associated with impairments in executive functions, which are important for self-regulation. There is promising evidence that interventions targeting parenting behaviour have the potential to remediate adversity-related biological and behavioural alterations.
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This study investigated multi-children parents’ (MCPs) experiences of support in their parental role by participating in parental group for MCPs. Focus group interviews were performed with 20 MCPs consisting of 9 mothers and 11 fathers, with a mean number of children of 2.35 per family. Each interview lasted about 1 hour, and it was analyzed by content analysis method. One theme was revealed: parental group for MCPs gives access to reflection and development on MCP issues. This related to 2 categories: support in the MCPs’ role through internal development and support in the MCPs’ role through external influences. The study’s conclusion highlights the support of MCPs in their parental role by attending a parental group for MCPs and should be offered to achieve empowerment. Clinical implications are that a mix of men and women with different numbers of children of various ages of siblings should compose parental groups for MCPs.
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The mechanisms linking childhood maltreatment and eating pathology are not fully understood. We examined the mediating role of limbic system dysfunction in the relationships between three forms of childhood maltreatment (parental psychological maltreatment, parental physical maltreatment, and parental emotional neglect) and eating disorder symptoms. A convenience sample of college women ( N = 246, M age = 19.62, SD = 2.41) completed measures of maltreatment (Parent-Child Conflict Tactics Scales and the Parental Bonding Instrument), limbic system dysfunction (Limbic System Questionnaire), and eating pathology (Eating Disorder Examination Questionnaire). We hypothesized that there would be an indirect effect of each type of childhood maltreatment on eating disorder symptoms via limbic system irritability. Results generally supported the hypotheses. Examination of the individual paths that defined the indirect effect indicated that higher reported childhood maltreatment was associated with greater limbic irritability symptoms, and higher limbic irritability symptomatology was related to higher total eating disorder scores. There were no significant direct effects for any of the proposed models. Findings are in line with research supporting the role of limbic system dysfunction as a possible pathway in the maltreatment-eating disorder link. Given that limbic system dysfunction may underlie behavioral symptoms of eating disorders, efforts targeting limbic system dysfunction associated with child maltreatment might best be undertaken at an early developmental stage, although interventions for college women struggling with eating disorders are also crucial.
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Objective: Smaller hippocampal volume has been reported in several stress-related psychiatric disorders, including posttraumatic stress disorder (PTSD), borderline personality disorder with early abuse, and depression with early abuse. Patients with borderline personality disorder and early abuse have also been found to have smaller amygdalar volume. The authors examined hippocampal and amygdalar volumes in patients with dissociative identity disorder, a disorder that has been associated with a history of severe childhood trauma. Method: The authors used magnetic resonance imaging to measure the volumes of the hippocampus and amygdala in 15 female patients with dissociative identity disorder and 23 female subjects without dissociative identity disorder or any other psychiatric disorder. The volumetric measurements for the two groups were compared. Results: Hippocampal volume was 19.2% smaller and amygdalar volume was 31.6% smaller in the patients with dissociative identity disorder, compared to the healthy subjects. The ratio of hippocampal volume to amygdalar volume was significantly different between groups. Conclusions: The findings are consistent with the presence of smaller hippocampal and amygdalar volumes in patients with dissociative identity disorder, compared with healthy subjects.
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In the laboratory rat and guinea pig, glucocorticoids (GCs), the adrenal steroids that are secreted during stress, can damage the hippocampus and exacerbate the hippocampal damage induced by various neurological insults. An open question is whether GCs have similar deleterious effects in the primate hippocampus. In fact, we showed that sustained and fatal stress was associated with preferential hippocampal damage in the vervet monkey; however, it was not possible to determine whether the excessive GC secretion that accompanied such stress was the damaging agent. The present study examines this possibility. Pellets of cortisol (the principal GC of primates) were stereotaxically implanted into hippocampi of 4 vervet monkeys; contralateral hippocampi were implanted with cholesterol pellets as a control. One year later at postmortem, preferential damage occurred in the cortisol-implanted side. In the cholesterol side, mild cell layer irregularity was noted in 2 of 4 cases. By contrast in the cortisol-exposed hippocampi, all cases had at least 2 of the following neuropathologic markers: cell layer irregularity, dendritic atrophy, soma shrinkage and condensation, or nuclear pyknosis. Damage was severe in some cases, and was restricted to the CA3/CA2 cellfield. This anatomical distribution of damage, and the cellular features of the damage agree with that observed in instances of GC-induced toxicity in the rodent hippocampus, and of stress-induced toxicity in the primate hippocampus. These observations suggest that sustained GC exposure (whether due to stress, Cushings syndrome or exogenous administration) might damage the human hippocampus.
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Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence. Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.
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Variations in maternal care affect the development of individual differences in neuroendocrine responses to stress in rats. As adults, the offspring of mothers that exhibited more licking and grooming of pups during the first 10 days of life showed reduced plasma adrenocorticotropic hormone and corticosterone responses to acute stress, increased hippocampal glucocorticoid receptor messenger RNA expression, enhanced glucocorticoid feedback sensitivity, and decreased levels of hypothalamic corticotropin-releasing hormone messenger RNA. Each measure was significantly correlated with the frequency of maternal licking and grooming (all r's > −0.6). These findings suggest that maternal behavior serves to “program” hypothalamic-pituitary-adrenal responses to stress in the offspring.
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Cognitive event-related potentials (ERPs) were recorded from 23 maltreated and 21 nonmaltreated children. Children were presented with slides of Ekman photographs of asingle model posing an angry (25%), a happy (25%), or a neutral (50%) facial expression. In 1 of 2 counterbalanced target conditions, children were asked to press a button in response to the angry face; in the other target condition, they responded to the happy face. Both samples, as expected, exhibited the largest amplitude of the P300 component of the ERP to target stimuli and the smallest amplitude to nontargets. For nonmaltreated children, the average amplitude of P300 across slides was comparable for the 2 target conditions. In contrast, maltreated children displaed larger P300 ampltude to stimuli when they were directed to attend to angry, as opposd children displayed larger p300 amplitude to stimuli whe they were directed to attend to angry, as opposed to happy, targets. These reaults suggest different cognitive processing for positive versus negative affective expressions by children with histories of atypical emotiaonal exotional experiences.
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In this study, the authors examined time-varying associations between schizotypal (STPD), borderline (BPD), avoidant (AVPD), or obsessive-compulsive (OCPD) personality disorders and co-occurring Axis I disorders in 544 adult participants from the Collaborative Longitudinal Personality Disorders Study. The authors tested predictions of specific longitudinal associations derived from a model of crosscutting psychobiological dimensions (L. J. Siever & K. L. Davis, 1991) with participants with the relevant Axis I disorders. The authors assessed participants at baseline and at 6-, 12-, and 24-month follow-up evaluations. BPD showed significant longitudinal associations with major depressive disorder and posttraumatic stress disorder. AVPD was significantly associated with anxiety disorders (specifically social phobia and obsessive-compulsive disorder). Two of the four personality disorders under examination (STPD and OCPD) showed little or no association with Axis I disorders.
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Available research indicates that maltreated children frequently experience multiple types of maltreatment, although relatively few studies examine this issue directly. Review of existing studies also shows that, when investigated, maltreatment types are often correlated. However, from study to study the strength of associations among maltreatment types varies considerably, apparently due to methodological differences, such as differences in operational definitions of the maltreatment types, composition of samples and/or method of scaling used. Failure to account for overlap among maltreatment types can result in a misleading picture of a child’s trauma history. This in turn can lead to an inaccurate evaluation of the relationship between a child’s victimization experiences and later developmental outcomes. The wide variation in correlations among the maltreatment types from study to study raises questions about the validity of the different operational definitions used. Improving the construct validity of the maltreatment type measures is proposed as the means to obtaining more consistent results. Steps by which to achieve this objective are outlined.
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The cerebellum is a brain region recognized primarily in the coordination of movement and related accessory motor functions. In addition, emerging evidence implicates the cerebellum in cognitive processes and suggests that this brain region might be subject to experience-dependent changes in structure. Therefore, the aim of this study was to evaluate the role of early environmental deprivation in the maturation of the cerebellum and aspects of cognitive development. Structural magnetic resonance imaging volumes of 12 cerebellar sub-regions from 31 previously neglected and 30 typically developing children were compared with subjects' corresponding neuropsychological test scores. Neglected children had smaller volume of the superior-posterior cerebellar lobes. Moreover, superior-posterior lobe volume was found to mediate neuropsychological test performance differences between groups, with larger volumes yielding better outcomes on tests of memory and planning. These data support the importance of experience-dependent changes in cerebellar structure and highlight the role of the cerebellum in higher cognitive functions.
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Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.
Conference Paper
Objective: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). Method: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Results: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. Conclusions: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.
Article
The effects of maternal proximity on the behavioral and physiological responses of infant rhesus macaques during 4 days of total or adjacent separations from the mother were studied. The 6 infants tested showed behavioral responses that differentiated the two separation conditions. Major differences were found in the quantity and quality of vocalizations, the occurrence of cage-biting and cage-shaking behavior, object exploration, and hunched and freezing postures. In particular, the structure of coo vocalizations clearly discriminated between the presence or the absence of the mother during separation. Cerebrospinal fluid (CSF) concentrations of dopamine and serotonin metabolites did not discriminate between the two separation conditions but showed a transient elevation at 24 hr after separation and were not different from baseline by 96 hr after separation. In contrast, both the plasma cortisol and the CSF norepinephrine metabolite responses tended to be greater and to persist for a longer period of time when infants were totally isolated. The results are discussed within the context of attachment and coping theories. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
This chapter focuses on the role of the hippocampus in learning and memory processes. The study was initiated in 1957, after a report showed remarkably severe amnesia in a patient resulting from the surgical removal of the hippocampal formation and a large amount of the adjacent tissue in the medial temporal lobes. This led to the universal consensus that the hippocampus is involved in learning and memory. The unique contribution of hippocampus in learning includes its role in spatial processing, working memory, relational learning, episodic memory, context processing, declarative memory, and the encoding of experiences in general. This chapter evaluates the potential relationship between neural representation by individual hippocampal neurons and learning and memory. The most commonly reported behavioral correlate of hippocampal output neurons (pyramidal cells) is location-selective firing, referred to as place fields. The chapter provides evidence that demonstrates the sensory and movement responsiveness of place fields. It also presents a context discrimination hypothesis to evaluate the role that place fields may play in hippocampal-dependent mnemonic functions.
Article
Objectives. —To determine the prevalence of childhood physical or sexual abuse in women seen in primary care practices; to identify physical and psychologic problems associated with that abuse; and to compare the effects of childhood physical vs sexual abuse and childhood vs adult abuse.
Article
concerned with the normal and abnormal development of the mechanisms and processes involved in emotion activation, emotion expressions and emotion–related behavior, the feeling/experiential component of emotions, and emotion-cognition relations / when is the influence of emotion adaptive and when maladaptive, and under what circumstances is it one or the other / what sorts of emotion-related biological, sociocultural, and cognitive processes lead to developmental psychopathology / can phenomena as seemingly disparate as genetic anomalies and inappropriate belief systems be implicated / present a few general remarks on the neural basis of emotions and . . . focus on those aspects that have clear implications for developmental psychopathology (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
This study examined the effects of stressful environments on physiological and affective functioning among 131 maltreated school-aged children attending a summer day camp. Sixty-six nonmaltreated children also attending the camp served as a comparison group. Salivary Cortisol measures were obtained daily at 10:00 a.m. and at 4:00 p.m. Depression was measured using the Child Depression Inventory. Children with scores of 19 or higher were classified as depressed. Internalizing and externalizing behavior problems were determined from the Teacher Report Form of the Child Behavior Checklist. Children with t scores of 70 or higher were classified as having clinical levels of these problems. Maltreated children had slightly elevated afternoon Cortisol concentrations, but their morning concentrations did not differ significantly from those of nonmaltreated children. Neither clinical levels of depression, internalizing, or externalizing problems were predictive of the elevated afternoon values. Depression among maltreated children was, however, associated with altered activity of the hypothalamic-pituitary-adrenocortical (HPA) axis. Depressed maltreated children had lower morning Cortisol concentrations compared to nondepressed maltreated children and were more likely to show a rise rather than the expected decrease in Cortisol from morning to afternoon. These data replicated earlier findings. There was no evidence that depressed, nonmaltreated children exhibited this change in diurnal Cortisol activity.
Article
Salivary cortisol concentrations (10:30–11:30 a.m.) and social behavior (observations and teacher reports) were examined in 33 maltreated (26 boys) and 16 comparison (8 boys) children. The maltreated children were studied for 31 days while they attended a therapeutic preschool for abused and neglected children. Children in the comparison sample were studied while attending a preschool serving economically disadvantaged families. Each child's cortisol values over days were used to compute measures of basal activity (median cortisol) and reactivity (ratio of quartile ranges). Median cortisol was not significantly correlated with social behavior measures. Cortisol reactivity was positively correlated with social competence and negatively correlated with shy/internalizing behavior. Maltreated children exhibited less cortisol reactivity then did comparison children. Maltreated children also scored lower in social competence and higher in shy/internalizing and acting out/externalizing behaviors. In additional analyses, maltreated children failed to show elevations in cortisol on days of high versus low social conflict in the classroom. Social competence was also found to correlate positively with cortisol levels on high-conflict days. In all, the results suggest a reduction in cortisol reactivity in maltreated children related to the impairment in social competence frequently noted among these children.
Article
The role of the mother-toddler attachment relationship in moderating the relations between behavioral inhibition and changes in salivary cortisol levels in response to novel events was examined in 77 18-month-olds. Behavioral inhibition was determined by observing toddler inhibition of approach to several novel events. Attachment security to mother was assessed using the Ainsworth Strange Situation. Changes in salivary cortisol were used to index activity of the stress-sensitive hypothalamic-pituitary-adrenocortical (HPA) system. In addition, toddler coping behaviors and the behaviors used by mothers to help toddlers manage novel events were examined. Elevations in cortisol were found only for inhibited toddlers in insecure attachment relationships. Mothers in these relationships appeared to interfere with their toddlers' coping efforts. These results are discussed in the context of a coping model of the relations between temperament and stress reactivity.
Article
Animal studies have shown that mother–infant interactions can have long-term impacts on areas of the brain that regulate fearful behavior and the physiology of stress. Here, the research on human infants and children is reviewed with an eye to whether early experiences have similar effects in our species. Research shows that during the first year, sensitive and responsive caregiving becomes a powerful regulator of emotional behavior and neuroendocrine stress hormone activity in young children. Indeed, quality-of-care effects can be detected for children throughout the preschool years. Reviewed research suggests that temperament affects the likelihood that children will show increases in stress hormones as the quality of their care decreases. Finally, we review the literature on stress hormone activity in children who have been maltreated early in life, and explore the critical question of whether enhancing care later in development can reverse the effects on behavior and neurobiology of early adverse experiences. ©2003 Michigan Association for Infant Mental Health.
Article
Sensitization of stress-responsive neurobiological systems as a possible consequence of early adverse experience has been implicated in the pathophysiology of mood and anxiety disorders. In addition to early adversities, adulthood stressors are also known to precipitate the manifestation of these disorders. The present study sought to evaluate the relative role of early adverse experience vs. stress experiences in adulthood in the prediction of neuroendocrine stress reactivity in women. A total of 49 women (normal volunteers, depressed patients, and women with a history of early abuse) underwent a battery of interviews and completed dimensional rating scales on stress experiences and psychopathology, and were subsequently exposed to a standardized psychosocial laboratory stressor. Outcome measures were plasma adrenocorticotropin (ACTH) and cortisol responses to the stress test. Multiple linear regression analyses were performed to identify the impact of demographic variables, childhood abuse, adulthood trauma, major life events in the past year, and daily hassles in the past month, as well as psychopathology on hormonal stress responsiveness. Peak ACTH responses to psychosocial stress were predicted by a history of childhood abuse, the number of separate abuse events, the number of adulthood traumas, and the severity of depression. Similar predictors were identified for peak cortisol responses. Although abused women reported more severe negative life events in adulthood than controls, life events did not affect neuroendocrine reactivity. The regression model explained 35% of the variance of ACTH responses. The interaction of childhood abuse and adulthood trauma was the most powerful predictor of ACTH responsiveness. Our findings suggest that a history of childhood abuse per se is related to increased neuroendocrine stress reactivity, which is further enhanced when additional trauma is experienced in adulthood. Depression and Anxiety 15:117–125, 2002.
Article
Children who enter foster care have usually experienced maltreatment as well as disruptions in relationships with primary caregivers. These children are at risk for a host of problematic outcomes. However, there are few evidence-based interventions that target foster children. This article presents preliminary data testing the effectiveness of an intervention, Attachment and Biobehavioral Catch-up, to target relationship formation in young children in the foster care system. Children were randomly assigned to the experimental intervention that was designed to enhance regulatory capabilities or to a control intervention. In both conditions, the foster parents received in-home training for 10 weekly sessions. Post-intervention measures were collected 1 month following the completion of the training. Outcome measures included children's diurnal production of cortisol (a stress hormone), and parent report of children's problem behaviors. Children in the experimental intervention group had lower cortisol values than children in the control intervention. Also, the experimental intervention parents reported fewer behavior problems for older versus younger foster children. Results provide preliminary evidence of the effectiveness of an intervention that targets children's regulatory capabilities and serve as an example of how interventions can effectively target foster children in the child welfare system.
Article
Processing of emotion information by maltreated and control children was assessed with event-related brain potentials (ERPs). Maltreated children, for whom negative facial displays may be especially salient, and demographically comparable peers were tested to increase knowledge of differential processing of emotion information. ERPs were measured while children responded to pictures depicting facial displays of anger, fear, and happiness. Maltreated children showed larger P3b amplitude when angry faces appeared as targets than did control children; the two groups did not differ when targets were either happy or fearful facial expressions or for nontargets of any emotional content. These results indicate that aberrant emotional experiences associated with maltreatment may alter the allocation of attention and sensitivity that children develop to process specific emotion information.
Article
Early-life stimulation (e.g. brief handling) attenuates the behavioral and neuroendocrine responses to stressors encountered in adulthood, particularly with respect to activation of hypothalamic-pituitary-adrenal (HPA) activity. In contrast, if neonates were subjected to a more severe stressor, such as protracted separation from the dam or exposure to an endotoxin, then the adult response to a stressor was exaggerated. These early-life experiences program HPA functioning, including negative feedback derived from stimulation of hippocampal glucocorticoid receptors, and corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) coexpression in PVN neurons, to modify the response to subsequent stressor experiences. The persistent variations of HPA activity observed in handled/stimulated animals may stem from alterations in dam–pup interactions (e.g. increased arched-back feeding, licking, grooming). In addition genetic makeup is critical in determining stress reactivity. For instance, BALB/cByJ mice are more reactive to stressors than C57BL/6ByJ mice, exhibiting greater HPA hormonal alterations and behavioral disturbances. BALB/cByJ also fail to acquire a spatial learning response in a Morris water-maze paradigm, which has been shown to be correlated with hippocampal cell loss associated with aging. Early-life handling of BALB/cByJ mice prevented these performance deficits and attenuated the hypersecretion of ACTH and corticosterone elicited by stressors. The stressor reactivity may have been related to maternal and genetic factors. When BALB/cByJ mice were raised by a C57BL/6ByJ dam, the excessive stress-elicited HPA activity was reduced, as were the behavioral impairments. However, cross-fostering the more resilient C57BL/6ByJ mice to a BALB/cByJ dam failed to elicit the behavioral disturbances. It is suggested that genetic factors may influence dam–pup interactive styles and may thus proactively influence the response to subsequent stressors among vulnerable animals. In contrast, in relatively hardy animals the early-life manipulations may have less obvious effects.
Article
Total midsagittal area and seven subdivisions of the corpus callosum were measured on magnetic resonance images of 114 healthy boys and girls, aged 4 to 18. Striking variability of size was noted for all measures. Total midsagittal corpus callosum area increased in a robust and linear fashion from ages 4 to 18 (slope = 13.1 mm2/year, P = 0.0001 and slope = 11.1 mm2/year, P = 0.0001 for females and males, respectively). Posterior and mid regions demonstrated greater age-related changes than anterior regions with the rostrum and genu (anterior regions) having reached adult sizes in the youngest of our subjects. There were no significant effects of sex for any measures. These findings support anatomical studies indicating ongoing myelination of higher association areas throughout adolescence, but raise intriguing questions about anterior-posterior gradients of interhemispheric myelination.
Article
Background: The authors previously reported elevated cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed by mothers undergoing experimentally imposed unpredictable foraging conditions in comparison to normally reared controls. The purpose of the present study was to determine if these changes would endure into young adulthood. Methods: Cisternal CSF samples were obtained from those unpredictably reared young adult primates who had been previously studied as juveniles and age-matched ad libitum normally reared controls. Samples were assayed for CSF CRF. Results: Concentrations of CSF CRF were significantly elevated in the unpredictably reared sample in comparison to the ad libitum-reared control group. A significant positive correlation was noted between juvenile and young adult CSF CRF values within the unpredictably reared cohort. Conclusions: Disturbances of maternal-infant attachment processes have an enduring impact on primate CRF function into young adulthood. The CRF elevations following unpredictable maternal foraging conditions appear traitlike in nature.
Article
At its simplest, voxel-based morphometry (VBM) involves a voxel-wise comparison of the local concentration of gray matter between two groups of subjects. The procedure is relatively straightforward and involves spatially normalizing high-resolution images from all the subjects in the study into the same stereotactic space. This is followed by segmenting the gray matter from the spatially normalized images and smoothing the gray-matter segments. Voxel-wise parametric statistical tests which compare the smoothed gray-matter images from the two groups are performed. Corrections for multiple comparisons are made using the theory of Gaussian random fields. This paper describes the steps involved in VBM, with particular emphasis on segmenting gray matter from MR images with nonuniformity artifact. We provide evaluations of the assumptions that underpin the method, including the accuracy of the segmentation and the assumptions made about the statistical distribution of the data.
Article
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.
Article
The hippocampus is vulnerable to the damaging actions of insults such as transient ischemia and repetitive stimulation, as well as repeated exposure to exogenous glucocorticoids. This study investigated effects of a repeated psychological stressor, restraint, on the CA3 pyramidal neurons which are vulnerable to damage by repetitive stimulation. Repeated daily restraint stress for 21 days caused apical dendrites of CA3 pyramidal neurons to atrophy, while basal CA3 dendrites did not change. Rats undergoing this treatment were healthy and showed some adaptation of the glucocorticoid stress response over 21 days; however, stress reduced body weight gain by 14% and increased adrenal weight relative to body weight by 20%. Results are discussed in relation to the possible role of adrenal steroids and excitatory amino acids.
Article
An investigation of the association between diurnal changes in cortisol and DHEA levels, or in the cortisol/DHEA ratio at five different time points at presentation, and the occurrence of undesirable life events (losses, dangers to self and others, disappointments) during follow-up, and the outcome of major depression at 36 weeks were investigated. Psychosocial and endocrine assessment of a consecutive cohort (N = 68) of 8- to 16-year-old subjects with first episode major depression reassessed 12 months after presentation using a repeat measures design. Higher cortisol/DHEA ratios at 20.00 or 24.00 h predicted persistent major depression. Basal levels of either hormone alone or cortisol/DHEA ratios at the other three time points (08.00, 12.00 or 16.00 h) did not. High cortisol/DHEA ratios (i.e. values greater than the 60th percentile) at both evening points (20.00 and 24.00 h) also predicted the occurrence of subsequent disappointing life events but no other category of undesirable event. Both high evening cortisol/DHEA ratio at 20.00 h and one or more severely disappointing life events between presentation and follow-up predicted persistent major depression: 86% of subjects with both of these factors were still depressed at 36 weeks whereas 81% with neither factor were not. The finding that it is depressed subjects with high cortisol/DHEA ratios at presentation who are specifically at risk for subsequent disappointing life events suggests a putative role for these adrenal steroids in abnormal cognitive or emotional processes associated with disturbed interpersonal behaviour.
Article
Arousal-regulating mechanisms are important in explaining individual differences in antisocial behavior. Alterations in salivary cortisol concentration and cardiovascular activity were studied in 21 boys with oppositional defiant disorder (ODD) and 31 normal controls (NC) during a 2-hour stressful procedure involving frustration and provocation. Baseline levels of heart rate (HR) were significantly lower in the ODD group, but their HR levels were higher during provocation and frustration. Cortisol levels in the ODD group were overall lower than those of the NC group, and the effect of stress seemed to be minimal and similar for both groups; however, individual differences were large. Since anxiety plays an important mediating role in cortisol response, subjects were divided into one of four groups based on the intensity of their externalizing behavior and anxiousness. Cortisol increase due to stress exposure was strongest in highly externalizing and highly anxious subjects; cortisol decrease was strongest in those subjects who were high in externalizing behavior and low in anxiousness. The results of the study support an important role for hypothalamic-pituitary-adrenal axis sympathetic autonomic functioning in persistent antisocial behavior in young boys.
Article
Background: Childhood sexual abuse (CSA) has been associated with alterations in brain morphology using region of interest analyses that have focused on stress-sensitive target regions. This study was designed to ascertain the effects on gray matter volume (GMV) of exposure to CSA in healthy young adult college students selected based on exposure history regardless of psychiatric outcome. Voxel-based morphometry (VBM) provided unbiased delineation of the most significantly affected brain regions. Methods: High-resolution T1-weighted magnetic resonance imaging (MRI) datasets were obtained for 23 unmedicated female subjects with CSA and 14 healthy female control subjects of equivalent age and socioeconomic status with no history of trauma. Cortical surface-based analysis (FreeSurfer) was performed to verify VBM results. Results: Gray matter volume was reduced by 12.6% and 18.1% in right and left primary visual (V1) and visual association cortices of abused subjects. This reduction was directly related to duration of CSA before age 12. Gray matter volume of left and right V1 correlated with measure of visual memory (r = .353, p = .032 and r = .448, p = .005). Cortical surface-based analysis indicated that GMV of abused subjects was reduced in the left fusiform (p = .004), left middle occipital (p = .04), and right lingual (p = .002) gyri. Conclusions: Early visual experience exerts a strong influence on the developing mammalian visual cortex. Present findings indicate that exposure to CSA may also affect the development of this region and are apparent even in a population of subjects who are sufficiently healthy to matriculate.