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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Despite growing attention to resilience following childhood maltreatment, it remains unclear how the development of resilience unfolds over time among child welfare-involved adolescents. Further, little is known about the immediate and enduring effects of two important attachments in children’s lives, namely caregiver–child relationship and deviant peer affiliation, on resilience development over time. This study sought to examine the ways in which caregiver–child relationships and deviant peer affiliation shape developmental trajectories of resilience among child welfare-involved youth. Data were drawn from the National Survey of Child and Adolescent Well-Being. Latent growth curve modeling was conducted on a sample of 711 adolescents. The results revealed that adolescents’ resilience increased across a 36-month period since initial contact with Child Protective Services. Better caregiver–child relationships were associated with a higher initial level of resilience among adolescents, whereas higher deviant peer affiliation was associated with a lower initial level of resilience. Significant lagged effects were also found; caregiver–child relationship quality and deviant peer affiliation at baseline were associated with resilience at 18 months after. The findings suggest that interventions that aim to promote positive caregiver–child relationships and prevent deviant peer relationships may help foster resilience among adolescents who have experienced child maltreatment.
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Adversity early in life is common and is a major risk factor for the onset of psychopathology. Delineating the neurodevelopmental pathways by which early adversity affects mental health is critical for early risk identification and targeted treatment approaches. A rapidly growing cross-species literature has facilitated advances in identifying the mechanisms linking adversity with psychopathology, specific dimensions of adversity and timing-related factors that differentially relate to outcomes, and protective factors that buffer against the effects of adversity. Yet, vast complexity and heterogeneity in early environments and neurodevelopmental trajectories contribute to the challenges of understanding risk and resilience in the context of early adversity. In this overview, the author highlights progress in four major areas-mechanisms, heterogeneity, developmental timing, and protective factors; synthesizes key challenges; and provides recommendations for future research that can facilitate progress in the field. Translation across species and ongoing refinement of conceptual models have strong potential to inform prevention and intervention strategies that can reduce the immense burden of psychopathology associated with early adversity.
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In this paper, I examine my work with Richard using neuro-psychoanalytic concepts to depict the recovery of a live object that had been buried with his mother, three years before. I ask whether encouraging alpha function in a traumatised child who might once have had access to a functioning thinking mind may be damaging to a core protective aspect of his personality: a ‘robot’ mechanism that switches on in his mind/body, to protect him from a tragic sequence of events. I suggest that psychotherapy with a child in a frozen state is a delicate process, involving the avoidance of triggering defensive aspects of the personality, while helping the child learn other, more protective aspects available to him. I show how incorporating the ‘music of silence’ and the spoken word can help a traumatised child recover emotional fluency. I draw on the neurobiological research of Bessel Van der Kolk and Stephen Porges to show how working in the bodily countertransference can be important in helping traumatised patients. The analysis extends to examining child psychotherapy literature around endings, with a focus on avoiding retraumatisation when finishing work with a bereaved child.
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Background There are currently 2.2 million people incarcerated in U.S. prisons and jails, representing a 500% increase over the past 40 years. An emerging literature suggests the impact of mass incarceration extends beyond the prison, jail, or detention center to the families of incarcerated individuals. Less scholarship has considered consequences of parental incarceration for their children's physical health. Methods We conduct a critical review of the literature investigating an association between parental incarceration and children's physical health outcomes from infancy to adulthood. Results Studies varied substantially in study design, sample composition, and methodological approach. Most studies suggest an association between parental incarceration and adverse physical health outcomes. Evidence is more consistent for outcomes such as infant and child mortality, lower healthcare access, and negative health behaviors and more mixed for measures such as self-reported/general health. Conclusion We propose a multilevel model of mechanistic pathways to stimulate future research on the potential pathways through which parental incarceration could influence children's physical health.
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Background: Early adversity is believed to alter the body's stress-response systems, putting children at increased risk for somatic and mental health problems. However, it remains unclear whether such alterations normalize under improved caregiving experiences. Thus, the goal of the present study was to investigate (a) whether children in foster care show endocrine and immunological alterations relative to children living with their biological families, (b) whether these alterations change over time spent with the foster family, and (c) whether the alterations are modulated by current caregiving experiences. Methods: A total of 94 children in foster care and 157 biological children, aged two to seven years, took part in a longitudinal study with three assessments conducted over a 12-month study period. At the initial assessment, children lived for an average of 18 months with their current foster families. Children's cortisol, dehydroepiandrosterone (DHEA) and progesterone concentrations and cortisol/DHEA ratios were measured in scalp hair and children's secretory immunoglobulin A (sIgA) levels in saliva. Caregiving quality was assessed based on caregiver-reports and observational measures of caregiver-child interactions. Results: Children in foster care had lower cortisol/DHEA ratios and higher progesterone concentrations than biological children, while no group differences were found for cortisol, DHEA or sIgA. Time spent with the current foster family did not significantly influence the child's endocrine or immunological markers. Importantly, caregiving quality modulated cortisol/DHEA ratios and sIgA concentrations: children in foster care of lower caregiving quality had lower cortisol/DHEA ratios than children in foster care of higher caregiving quality and showed decreasing, rather than increasing, sIgA concentrations across the study period. Conclusions: Our results indicate that caregiving quality in the foster family may have an important modulating effect on selected indicators of the child's stress response and could thereby mitigate the possible consequences of early childhood adversity.
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Mentoring‐based interventions show promise among children in foster care, but previous research suggests that some benefit more than others. Because children in foster care experience relationship disruptions that could affect mentoring effectiveness, we examined whether children’s relational histories at baseline (i.e., relationship quality with birth parents, relationship quality with foster parents, caregiver instability, and previous mentoring experience) moderated the impact of a mentoring intervention on children’s mental health, trauma symptoms, and quality of life. Participants included 426 racially and ethnically diverse children (age: 9–11; 52% male) who participated in a randomized controlled trial of the Fostering Healthy Futures program (FHF), a 9‐month one‐to‐one mentoring and skills group intervention. Results showed that relationship quality with foster parents and prior mentoring experience did not moderate intervention impact. Relationship quality with birth parents and caregiver instability pre‐program, however, moderated the effect on some outcomes. The impact on quality of life was stronger for children with weaker birth parent relationships and fewer caregiver changes. Likewise, the impact on trauma symptoms was stronger for those with fewer caregiver changes. Overall, FHF seems to positively impact children with varied relational histories, yet some may derive more benefits – particularly those with fewer caregiver changes pre‐program. Children’s early relational histories may affect the impact of mentoring programs. Fostering Healthy Futures (FHF) improves mental health of children with varied relational histories. FHF’s impact on trauma symptoms was stronger for children with fewer caregiver changes pre‐program. FHF’s impact on quality of life was stronger for children with fewer caregiver changes pre‐program. FHF’s impact on quality of life was stronger for children with poorer birth parent relationships.
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Background There is a lack of studies examining psychosocial functioning in patients with non-suicidal self-injury (NSSI), especially in adolescents, and rates of impaired functioning in existing literature vary considerably. These variations may be attributable to further risk factors that influence psychosocial functioning. Thus, the aim of the study was to examine whether adolescent NSSI patients with childhood maltreatment (CM), a known risk factor for lower psychosocial functioning, may differ from adolescent NSSI patients without CM, and whether these differences may be explained by the severity of comorbid disorders. Specifically, we examined whether severity of borderline personality disorder (BPD), depression and posttraumatic stress disorder may explain differences in psychosocial functioning in NSSI patients with and without CM. Methods Data of 368 adolescents with NSSI disorder from an outpatient clinic were analyzed using structural equation modeling. Clinicans’ rating of the Global Assessment of Functioning Scale (GAF) was collected, in addition to clinical interviews. Results Results indicate that GAF scores were lower among NSSI patients with CM and that the difference in psychosocial functioning between these groups was explained by BPD and depression severity. Conclusions Psychosocial functioning in NSSI patients varies depending on whether they have experienced CM or not. Specifically, these differences seem to be attributable to higher BPD and depression severity in adolescent NSSI patients with CM. Clinicians should ensure to assess CM and focus on BPD and depression severity in this population. Treatment of BPD and depression may notably reduce psychosocial impairment in NSSI patients with CM.
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Childhood maltreatment and adverse childhood experiences (ACEs) are two primary forms of interpersonal victimization that have been associated with a host of deleterious health outcomes. Studies over the past decade have begun to use a range of biologically informed methods to better understand the role that biology plays in the relationship between maltreatment, ACEs, and later life outcomes. This line of research has shown that both forms of victimization occur at sensitive periods of development, which can increase the likelihood of “getting under the skin” and influence health and behavior across the life course. This review examines the current state of knowledge on this hypothesis. One hundred and ninety-nine studies are included in this systematic review based on criteria that they be written in English, use a biologically informed method, and be conducted on samples of humans. Results reveal that latent additive genetic influences, endocrinological biomarkers, polygenic risk scores, and neurobiological features are commonly associated with exposure and response to childhood maltreatment and ACEs. The implication of these findings for the existing body of research on early life victimization and recommendations for future research are discussed.
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Life stress increases risk for multiple forms of psychopathology, in part by altering neural processes involved in performance monitoring. However, the ways in which these stress-cognition effects are influenced by the specific timing and types of life stressors experienced remains poorly understood. To address this gap, we examined how different social-psychological characteristics and developmental timing of stressors are related to the error-related negativity (ERN), a negative-going deflection in the event-related potential (ERP) waveform that is observed from 0 to 100 ms following error commission. A sample of 203 emerging adults performed an ERN-eliciting arrow flanker task and completed an interview-based measure of lifetime stress exposure. Adjusting for stress severity during other developmental periods, there was a small-to-medium effect of stress on performance monitoring, such that more severe total stress exposure, as well as more severe social-evaluative stress in particular, experienced during early adolescence significantly predicted an enhanced ERN. These results suggest that early adolescence may be a sensitive developmental period during which stress exposure may result in lasting adaptations to neural networks implicated in performance monitoring.
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Extensive research has demonstrated that rs1360780, a common single nucleotide polymorphism within the FKBP5 gene, interacts with early‐life stress in predicting psychopathology. Previous results suggest that carriers of the TT genotype of rs1360780 who were exposed to child abuse show differences in structure and functional activation of emotion‐processing brain areas belonging to the salience network. Extending these findings on intermediate phenotypes of psychopathology, we examined if the interaction between rs1360780 and child abuse predicts resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. We analyzed data of young European adults from the general population (N = 774; mean age = 18.76 years) who took part in the IMAGEN study. In the absence of main effects of genotype and abuse, a significant interaction effect was observed for rsFC between the right centromedial amygdala and right posterior insula (p < .025, FWE‐corrected), which was driven by stronger rsFC in TT allele carriers with a history of abuse. Our results suggest that the TT genotype of rs1360780 may render individuals with a history of abuse more vulnerable to functional changes in communication between brain areas processing emotions and bodily sensations, which could underlie or increase the risk for psychopathology. In 774 young European adults, we examined if child abuse and rs1360780 of the FKBP5 gene interact in predicting resting‐state functional connectivity (rsFC) between the amygdala and other areas of the salience network. An interaction was found in rsFC with the right posterior insula, driven by stronger rsFC in TT allele carriers with a history of abuse. After exposure to childhood abuse, individuals with the rs1360780 TT genotype may become more vulnerable to develop psychopathology due to altered amygdala functional connectivity.
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Several decades of neuroimaging research in psychiatry have shed light on structural and functional neural abnormalities associated with individual psychiatric disorders. However, there is increasing evidence for substantial overlap in the patterns of neural dysfunction seen across disorders, suggesting that risk for psychiatric illness may be shared across diagnostic boundaries. Gaining insights on the existence of shared neural mechanisms which may transdiagnostically underlie psychopathology is important for psychiatric research in order to tease apart the unique and common aspects of different disorders, but also clinically, so as to help identify individuals early on who may be biologically vulnerable to psychiatric disorder in general. In this narrative review, we first evaluate recent studies investigating the functional and structural neural correlates of a general psychopathology factor, which is thought to reflect the shared variance across common mental health symptoms and therefore index psychiatric vulnerability. We then link insights from this research to existing meta-analytic evidence for shared patterns of neural dysfunction across categorical psychiatric disorders. We conclude by providing an integrative account of vulnerability to mental illness, whereby delayed or disrupted maturation of large-scale networks (particularly default-mode, executive, and sensorimotor networks), and more generally between-network connectivity, results in a compromised ability to integrate and switch between internally and externally focused tasks.
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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 cafeteria diet (CD), an experimental diet that mimics the obesogenic Western diet, can impair memory in adult rats. However, the suckling period is also particularly susceptible to diet‐induced behavioural modification. Here, following exposure to CD feeding during lactation, 24‐ to 26‐day‐old offspring were tested to determine maternal dietary effects on either open field habituation, object location (OL) learning or on recency learning. Whereas no impact on habituation learning could be demonstrated, both OL and recency memory were impaired. In controls (C), OL memory was shown both after a 5 min (p < .05) or 60 min (p < .001) inter‐trial interval (ITI). After the 60 min ITI, the difference between C and CD was significant (p < .05). Learning did not occur in the CD group at any time point and was not observed after the 24hr ITI in in either group. Whereas control rats demonstrated intact recency memory (p < .00001), no learning occurred in the CD group. Both groups differed significantly in their exploration ratios (p < .01). This study suggests a detrimental effect of exposure to an unhealthy Western diet during lactation, on cognitive functions in adolescent rats. These results could have implications for human cognition in the context of obesity epidemic.
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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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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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Conference Paper
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.