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Schalinski I.,University of Konstanz | Teicher M.H.,Harvard University | Teicher M.H.,Developmental Biopsychiatry Research Program
PLoS ONE | Year: 2015

Dissociation, particularly the shutting down of sensory, motor and speech systems, has been proposed to emerge in susceptible individuals as a defensive response to traumatic stress. In contrast, other individuals show signs of hyperarousal to acute threat. A key question is whether exposure to particular types of stressful events during specific stages of development can program an individual to have a strong dissociative response to subsequent stressors. Vulnerability to ongoing shutdown dissociation was assessed in 75 inpatients (46M/29F, M =31±10 years old) with schizophrenia spectrum disorder and related to number of traumatic events experienced or witnessed during childhood or adulthood. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was used to collect retrospective recall of exposure to ten types of maltreatment during each year of childhood. Severity of shutdown dissociation was related to number of childhood but not adult traumatic events. Random forest regression with conditional trees indicated that type and timing of childhood maltreatment could predictably account for 31% of the variance (p < 0.003) in shutdown dissociation, with peak vulnerability occurring at 13-14 years of age and with exposure to emotional neglect followed by various forms of emotional abuse. These findings suggest that there may be windows of vulnerability to the development of shutdown dissociation. Results support the hypothesis that experienced events are more important than witnessed events, but challenge the hypothesis that "life-threatening" events are a critical determinant. © 2015 Schalinski, Teicher. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source


Teicher M.H.,Harvard University | Teicher M.H.,Developmental Biopsychiatry Research Program | Parigger A.,Developmental Biopsychiatry Research Program | Parigger A.,University of Konstanz
PLoS ONE | Year: 2015

There is increasing interest in childhood maltreatment as a potent stimulus that may alter trajectories of brain development, induce epigenetic modifications and enhance risk for medical and psychiatric disorders. Although a number of useful scales exist for retrospective assessment of abuse and neglect they have significant limitations. Moreover, they fail to provide detailed information on timing of exposure, which is critical for delineation of sensitive periods. The Maltreatment and Abuse Chronology of Exposure (MACE) scale was developed in a sample of 1051 participants using item response theory to gauge severity of exposure to ten types of maltreatment (emotional neglect, non-verbal emotional abuse, parental physical maltreatment, parental verbal abuse, peer emotional abuse, peer physical bullying, physical neglect, sexual abuse, witnessing interparental violence and witnessing violence to siblings) during each year of childhood. Items included in the subscales had acceptable psychometric properties based on infit and outfit mean square statistics, and each subscale passed Andersen's Likelihood ratio test. The MACE provides an overall severity score and multiplicity score (number of types of maltreatment experienced) with excellent test-retest reliability. Each type of maltreatment showed good reliability as did severity of exposure across each year of childhood. MACE Severity correlated 0.738 with Childhood Trauma Questionnaire (CTQ) score and MACE Multiplicity correlated 0.698 with the Adverse Childhood Experiences scale (ACE). However, MACE accounted for 2.00- and 2.07- fold more of the variance, on average, in psychiatric symptom ratings than CTQ or ACE, respectively, based on variance decomposition. Different types of maltreatment had distinct and often unique developmental patterns. The 52-item MACE, a simpler Maltreatment Abuse and Exposure Scale (MAES) that only assesses overall exposure and the original test instrument (MACE-X) with several additional items plus spreadsheets and R code for scoring are provided to facilitate use and to spur further development. © 2015 Teicher Parigger. Source


Sumner C.R.,BioBehavioral Diagnostics | Sumner C.R.,BioBehavioral Diagnostics | Haynes V.S.,i3 Global | Teicher M.H.,Harvard University | And 2 more authors.
Postgraduate Medicine | Year: 2010

Placebo response complicates the interpretation of treatment response in both clinical practice and clinical trials in youth with attention-deficit/hyperactivity disorder (ADHD). In a pilot study comparing subjective ADHD symptom rating scales with scores obtained using the Quotient™ ADHD System (an objective computerized technology for assessment of hyperactivity, inattention, and impulsivity in ADHD), it was found that agreement between these 2 measures was not as strong as anticipated. This observation prompted us to evaluate placebo responses associated with subjective and objective assessments. Eligible study participants aged 6 to 14  years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD diagnosis based on clinician interviews were randomized to 1 of 2 treatment sequence groups (placebo, low dose, and medium dose; or low dose, medium dose, and placebo) using either atomoxetine HCl or osmotic controlled-release (OROS) methylphenidate HCl as the active treatment in a 3-week, triple-blind (subject, parent, rater) trial. Subjects were exposed to placebo and different medication doses to evaluate the comparative sensitivity of objective and subjective measures in assessing changes in clinical condition. Placebo response was defined using 3 thresholds: any improvement, > 25% improvement, or > 40% improvement from baseline on Quotient™Global Scaled Score (QGSS) or the ADHD Rating Scale (ADHD-RS) Total score from baseline to the visit when placebo was administered. Lin's concordance correlation coefficient was used to measure agreement between baseline and placebo scores for the objective and subjective assessments. Of 30  subjects with placebo and baseline scores, 80%, 47%, and 27% met the 3 response thresholds (ie, any, > 25%, or > 40% improvement, respectively) on the ADHD-RS Total score compared with 27%, 7%, and 0% on the QGSS. Lin's concordance correlation coefficient was 0.81 and 0.39 for the QGSS and the ADHD-RS Total score, respectively. Although larger trials are warranted, we tentatively conclude that using objective measures and higher response thresholds may enhance assay sensitivity in clinical trials and hence limit necessary patient enrollments to rule out type II statistical error. © Postgraduate Medicine. Source


Teicher M.H.,Harvard University | Teicher M.H.,Developmental Biopsychiatry Research Program | Samson J.A.,Harvard University | Samson J.A.,Developmental Biopsychiatry Research Program
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2016

Background Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A key breakthrough has been the discovery that maltreatment alters trajectories of brain development. Methods This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so, we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress-induced damage. Results Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable. Conclusions Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies. Childhood maltreatment is the most important preventable cause of psychopathology, accounting for about almost half of the risk for childhood onset psychiatric disorders. A key discovery is that maltreatment alters trajectories of brain development. This review synthesizes neuroimaging findings in children who experienced caregiver neglect, as well as from studies in young people and adults who experienced physical, sexual and emotional abuse. Key findings are that childhood maltreatment is associated with consistent alterations in key regions of the brain and maltreatment is consistently associated with enhanced amygdala response to threatening stimuli and diminished striatal response to anticipated reward. Brain regions and pathways affected are predominantly part of circuits regulating threat detection and reward anticipation, with exposure to single types of abuse associated with specific alterations that convey the aversive experience. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex, however, as they are discernible in both susceptible and resilient individuals with maltreatment histories. Future studies will need to focus on mechanisms fostering resilience. Read the Commentary on this article at doi: 10.1111/jcpp.12540 © 2016 Association for Child and Adolescent Mental Health. Source


Teicher M.H.,Harvard University | Teicher M.H.,Developmental Biopsychiatry Research Program | Vitaliano G.D.,Harvard University | Vitaliano G.D.,Developmental Biopsychiatry Research Program
PLoS ONE | Year: 2011

Research on the consequences of witnessing domestic violence has focused on inter-adult violence and most specifically on violence toward mothers. The potential consequences of witnessing violence to siblings have been almost entirely overlooked. Based on clinical experience we sought to test the hypothesis that witnessing violence toward siblings would be as consequential as witnessing violence toward mothers. The community sample consisted of unmedicated, right-handed, young adults who had siblings (n = 1,412; 62.7% female; 21.8±2.1 years of age). History of witnessing threats or assaults to mothers, fathers and siblings, exposure to parental and sibling verbal abuse and physical abuse, sexual abuse and sociodemographic factors were assessed by self-report. Symptoms of depression, anxiety, somatization, anger-hostility, dissociation and 'limbic irritability' were assessed by rating scales. Data were analyzed by multiple regression, with techniques to gauge relative importance; logistic regression to assess adjusted odds ratios for clinically-significant ratings; and random forest regression using conditional trees. Subjects reported witnessing violence to siblings slightly more often than witnessing violence to mothers (22% vs 21%), which overlapped by 51-54%. Witnessing violence toward siblings was associated with significant effects on all ratings. Witnessing violence toward mother was not associated with significant effects on any scale in these models. Measures of the relative importance of witnessing violence to siblings were many fold greater than measures of importance for witnessing violence towards mothers or fathers. Mediation and structural equation models showed that effects of witnessing violence toward mothers or fathers were predominantly indirect and mediated by changes in maternal behavior. The effects of witnessing violence toward siblings were more direct. These findings suggest that greater attention be given to the effects of witnessing aggression toward siblings in studies of domestic violence, abuse and early adversity. © 2011 Teicher, Vitaliano. Source

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