Dissociation, particularly the shutting down of sensory, motor and speech systems, has been propo... more 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.
Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punis... more Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse.
Background: Individuals who were maltreated during childhood are faced with increased risks for d... more Background: Individuals who were maltreated during childhood are faced with increased risks for developing various psychological symptoms that are particularly resistant to traditional treatments. This pilot study investigated the effects of a mindfulness based behavioral intervention for young adults with a childhood maltreatment history. Methods: This study looked at self-report psychological questionnaires from 20 subjects (5 males) before and after a mindfulness-based behavioral intervention, compared to 18 subjects (6 males) in the waiting list control group (age range 22-29); all subjects experienced mild-to-moderate childhood maltreatment. We analyzed changes in stress, anxiety, depression, mindfulness and self-compassion related to the intervention with linear mixed effects models; we also analyzed the relationships among questionnaire score changes with partial correlation analyses and mediation analysis. Results: Linear mixed effects model analyses revealed significant group by time interaction on stress (p < 0.01), anxiety (p < 0.05), and self-compassion (p < 0.01), with the mindfulness group having significant reduction in stress and anxiety (p < 0.01), and significant increase in mindfulness (p < 0.05) and self-compassion (p < 0.001). Partial correlation analyses showed that among all subjects from both groups, changes in mindfulness positively correlated with changes in self-compassion (r = 0.578, p = 0.001), which negatively correlated with changes in depression (r = -0.374, p = 0.05) and anxiety (r = -0.395, p < 0.05). Changes in self-compassion mediated, in part, the relationship between changes in mindfulness and changes in anxiety (average causal mediation effect = -4.721, p < 0.05). We observed a dose-dependent effect of the treatment, i.e., the number of intervention sessions attended were negatively correlated with changes in stress (r = -0.674, p < 0.01), anxiety (r = -0.580, p < 0.01), and
Objective-Depression is the most common adult outcome of exposure to childhood sexual abuse (CSA)... more Objective-Depression is the most common adult outcome of exposure to childhood sexual abuse (CSA). In this study, we retrospectively assessed the length of time from initial abuse exposure to onset of a major depressive episode. Method-A community-based survey of childhood experiences in 564 young adults (ages 18 to 22 years) conducted between 1997 and 2001 identified 29 right-handed female subjects with CSA but no other exposure to trauma. Subjects were interviewed for lifetime history and age of onset of Axis I disorders using the Structured Clinical Interview for DSM-IV Axis I Disorders. Results-Sixty-two percent (n = 18) of the sexual abuse sample met full lifetime criteria for major depression. Episodes of depression emerged, on average, 9.2 ± 3.6 years after onset of exposure to sexual abuse. Mean survival time from onset of abuse to onset of depression for the entire sample was 11.47 years (95% CI: 9.80 -13.13 years). There was a surge in new cases between 12-15 years of age. Average time to onset of posttraumatic stress disorder was 8.0 ± 3.9 years. Conclusions-Exposure to CSA appears to sensitize women to the development of depression, and to shift age of onset to early adolescence. Findings from this formative study suggest that clinicians should not interpret the absence of symptoms at the time of CSA as a sign of resilience. Continued monitoring of victims of CSA as they pass through puberty is recommended. Reasons for the time lag between CSA and depression are proposed along with potential strategies for early intervention.
The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models h... more The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17M/35F, 25.4 ±3.1 years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10-11 years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose-response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range 11 -54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure
Journal of Child Psychology and Psychiatry, Feb 1, 2016
Background and Scope-Childhood maltreatment is the most important preventable cause of psychopath... more Background and Scope-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. 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. Findings-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. 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. Conclusion-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 increases risk for mood, anxiety, substance use and personality disorders ... more Childhood maltreatment increases risk for mood, anxiety, substance use and personality disorders and is associated with alterations in structure, function and connectivity of brain regions involved in emotional regulation. We sought to assess whether maltreatment was specifically associated with disturbances in positive or negative mood regulation. Ecological momentary ratings were collected with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six times per day over a week in 60 unmedicated participants (22 control, 38 maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a history of major depression but all were currently euthymic. Principal component analysis with varimax rotation was used to provide orthogonal measures of positive and negative valence, which were analyzed for indices of variability,
Journal of Child and Adolescent Psychopharmacology, Jun 1, 2008
Background and purpose: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent dis... more Background and purpose: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder that can respond dramatically to medication, if dose is appropriately titrated. Studies suggest that computer measures of attention cannot be used for titration as they show improvement on doses too low to produce clinical benefits. We assessed whether measures of motor activity and attention using the McLean Motion Attention Test (M-MAT™) could identify doses associated with optimal clinical response. Methods: Eleven boys (9.6 Ϯ 1.8 years), receiving treatment with methylphenidate, and meeting DSM-IV criteria for ADHD, participated in this triple-blind (parent, child, rater), within-subject, efficacy study. Subjects received 1 week each of placebo, low (0.4 mg/kg), medium (0.8 mg/kg), and high (1.5 mg/kg) daily doses of methylphenidate. Parents rated response using an index of clinical global improvement. Results: In 9/11 subjects, the dose that produced the best improvement on M-MAT™ measures was also the dose that produced the best clinical outcome (p Ͻ 10 Ϫ5 ). Parents rated response to this dose significantly better than response to previously prescribed treatment. Objective measures of primarily activity and secondarily attention responded to treatment in a manner concordant with clinical ratings, suggesting that these measures have ecological validity, and the potential to facilitate medication management and titration.
Background-Although the literature suggests that childhood maltreatment (CM) relates to adolescen... more Background-Although the literature suggests that childhood maltreatment (CM) relates to adolescent heavy episodic drinking (HED), few studies have examined the long-term effects of CM on adolescent HED. This study is the first to examine associations between exposure to CM and trajectories of HED from adolescence to young adulthood for the US population. Methods-Four waves of data from the National Longitudinal Study of Adolescent Health were used. A total of 8,503 adolescents followed from adolescence (7th-12th grades) into young adulthood (ages 24-32) were assessed on CM and past-year HED frequency. Using growth curve modeling, trajectories of adolescent HED were examined, with subtype, frequency, and severity of CM as the primary independent variables. All of our analyses controlled for common risk factors for adolescent HED, including demographics, parental and peer alcohol use, parental education and employment, family income, parent-child relationship, and adolescent depression. Results-After controlling for potential risk factors, neglect and physical abuse -both individually and in conjunction -were associated with faster increases in HED during adolescence and persistently elevated HED over much of adolescence and young adulthood. The frequency of neglect and physical abuse -individually and in conjunction -was also associated with the trajectory of HED, such that additional instances of these types of maltreatment were associated with faster increases in HED during adolescence and higher rates of peak use during young adulthood.
Zeitschrift Fur Klinische Psychologie Und Psychotherapie, Apr 1, 2014
Background: Adverse childhood experiences increase the risk of psychopathology and influence seve... more Background: Adverse childhood experiences increase the risk of psychopathology and influence severity of mental ill-health as well as treatment outcomes. Clinical psychological work requires validated instruments to comprehensively assess childhood adversities. Objective: This paper deals with the construction and psychometric evaluation of the German version of the modified "Adverse Childhood Experience" Index, called "Belastende Kindheitserfahrungen" (KERF). This instrument assesses childhood adversity in depth. Method: Based on interview data of 165 female subjects, ten subscales were modeled using Rasch-Models. Correlations with the CTQ (Childhood Trauma Questionnaire) and psychopathology were analyzed. Results: Subscales were modeled, with the support of conceptual approaches. Satisfying associations with the CTQ and psychopathology were found. Conclusions: KERF enables a valid and detailed assessment of childhood adversities.
Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans... more Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans, the amygdala develops rapidly during the first two years of life. Thus, disturbed care during this period may be particularly important to amygdala development. In the context of a 30-year longitudinal study of impoverished, highly stressed families, we assessed whether disorganization of the attachment relationship in infancy was related to amygdala volume in adulthood. Amygdala volumes were assessed among 18 low-income young adults (8M/10F, 29.33±0.49 years) first observed in infancy (8.5±5.6 months) and followed longitudinally to age 29. In infancy (18.58±1.02 mos), both disorganized infant attachment behavior and disrupted maternal communication were assessed in the standard Strange Situation Procedure (SSP). Increased left amygdala volume in adulthood was associated with both maternal and infant components of disorganized attachment interactions at 18 months of age (overall r = .679, p < .004). Later stressors, including childhood maltreatment and attachment disturbance in adolescence, were not significantly related to left amygdala volume. Left amygdala volume was further associated with dissociation and limbic irritability in adulthood. Finally, left amygdala volume mediated the prediction from attachment disturbance in infancy to limbic irritability in adulthood. Results point to the likely importance of quality of early care for amygdala development in human children as well as in rodents. The long-term prediction found here suggests that the first two years of life may be an early sensitive period for amygdala development during which clinical intervention could have particularly important consequences for later child outcomes.
Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for... more Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience (ACE) is another strong risk factor for later substance abuse. We therefore, sought to ascertain the relationship between morphological phenotypes of the lingula (Lobule I) of the anterior cerebellar vermis (ACV), and exposure to emotional (EM) versus physical (PM) maltreatment,on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54M/99F, 21.9±2.2 years) selected for imaging from a database of 1,402 community participants 18-25 years of age, who completed a detailed online screening instrument, and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (PM group, n=37); parental verbal abuse and/or witnessing domestic violence (EM group, n= 58); or had no history of maltreatment or Axis I disorders (n=58). The main outcomes measures consisted of the grey matter volume of Lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5-and 2.7-fold more alcohol, and used drugs 6.1-and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a novel, experientially-sensitive, phenotypic risk factor for enhanced alcohol and drug use, that perhaps modulates sensitivity to these agents.
Child and Adolescent Psychiatry and Mental Health, Mar 4, 2023
Background Exposure to potentially traumatic experiences (PTEs) is common among children and adol... more Background Exposure to potentially traumatic experiences (PTEs) is common among children and adolescents, but relatively little is known about the epidemiology of trauma and trauma-related psychopathology in children and youth. The present cross-sectional epidemiological study aimed to explore factors that is associated with posttraumatic stress symptoms (PTSS) in children. Method Data stem from the Bergen Child Study, a series of cross-sectional multi-phase surveys of children born between 1993 and 1995 in Bergen, Norway. The sample used is from the second wave of the Bergen Child Study (BCS) conducted in 2006, a two-phase study. The study entailed a detailed psychiatric evaluation using the Development and well-being assessment (DAWBA). The DAWBA was administered to parents or caregivers and covered diagnostic areas, child and family background, and child strengths. A total of 2043 parents participated. Out of the total sample, parents reported that 4.8% children had experienced PTEs at some point in their lives. The findings revealed current PTSS in 30.9% of children exposed to PTE, which was 1.5% of the total sample. None of the parents reported PTSS in their children over the threshold for diagnosing posttraumatic stress disorder (PTSD). The most common PTSS cluster was arousal reactivity (90.0%), followed by negative cognitions and mood (80%). The least frequent symptom cluster was intrusions (63.3%) and avoidance (60%). Children with PTSS were reported to live in families with significantly more family stressors (p = 0.001, d = 0.8) and had utilized significantly more sources for help relative to those without PTSS (p = 0.001, d = 0.75). The present population study on children revealed a lower prevalence rate of PTEs and PTSD than previous studies. It provided findings in the field of trauma on parent-reported PTSS and PTSD symptom clusters not restricted to the clinical level of PTSD. Lastly, it highlighted how family-life stressors and support differed between those who had PTSS and those with no PTSS.
Background-Childhood abuse is a major risk factor for psychopathology. Previous studies have iden... more Background-Childhood abuse is a major risk factor for psychopathology. Previous studies have identified brain differences in maltreated individuals but have not focused on potential differences in network architecture. Methods-High-resolution T1-weighted MRI scans were obtained from 265 unmedicated, righthanded 18-25-year-olds who were classified as maltreated (n=142, 55M/87F) or non-maltreated (n=123, 46M/77F) based on extensive interviews. Cortical thickness was assessed in 112 cortical regions (nodes) and inter-regional partial correlations across subjects were calculated to derive the lowest equivalent cost single-cluster group networks. Permutation tests were used to ascertain whether maltreatment was associated with significant alterations in key centrality measures of these regions and membership in the highly interconnected 'rich club'. Results-Marked differences in centrality (connectedness, 'importance') were observed in a handful of cortical regions. Left anterior cingulate had the second highest number of connections (degree centrality) and was a component of the 'rich club' in the control network but ranked low in connectedness (106 th of 112 nodes) in the network derived from maltreated-subjects (p<0.01). Conversely, right precuneus and right anterior insula ranked first and 15 th in degree centrality in the maltreated network versus 90 th (p=0.01) and 105 th (p<0.03) in the control network. Conclusions-Maltreatment was associated with decreased centrality in regions involved in emotional regulation and ability to accurately attribute thoughts or intentions to others and with enhanced centrality in regions involved in internal emotional perception, self-referential thinking and self-awareness. This may provide a potential mechanism for how maltreatment increases risk for psychopathology.
Six depressed patients free of recent serious suicidal ideation developed intense, violent suicid... more Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupa tion after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these pa tients had ever experienced a similar state during treat-• ment with any other psychotropic drug.
Severe early stress and maltreatment produces a cascade of events that have the potential to alte... more Severe early stress and maltreatment produces a cascade of events that have the potential to alter brain development. The first stage of the cascade involves the stress-induced programming of the glucocorticoid, noradrenergic, and vasopressin-oxytocin stress response systems to augment stress responses. These neurohumors then produce effects on neurogenesis, synaptic overproduction and pruning, and myelination during specific sensitive periods. Major consequences include reduced size of the mid-portions of the corpus callosum; attenuated development of the left neocortex, hippocampus, and amygdala along with abnormal frontotemporal electrical activity; and reduced functional activity of the cerebellar vermis. These alterations, in turn, provide the neurobiological framework through which early abuse increases the risk of developing post-traumatic stress disorder (PTSD), depression, symptoms of attention-deficit/hyperactivity, borderline personality disorder, dissociative identity disorder, and substance abuse.
Objective-Childhood maltreatment increases risk for psychopathology. For some highly prevalent di... more Objective-Childhood maltreatment increases risk for psychopathology. For some highly prevalent disorders (i.e., major depression, substance abuse, anxiety disorders and posttraumatic stress disorder) there is a substantial subset of individuals with maltreatment histories and a substantial subset without. Do those with maltreatment histories represent a clinically and biologically distinct subtype? Method-The authors review literature on maltreatment as a risk factor for these disorders and on the clinical differences between individuals with and without maltreatment who share the same diagnoses. Neurobiological findings in maltreated individuals are reviewed and compared to findings reported for these disorders. Results-Maltreated individuals with depressive, anxiety and substance use disorders show an earlier age of onset, greater symptom severity, more comorbidity, increased risk for suicide and poorer treatment response than non-maltreated individuals with the same diagnoses. Imaging findings associated with these disorders, such as reduced hippocampal volume and amygdala hyperreactivity are more consistently observed in maltreated individuals and may represent a maltreatment-related risk factor. Maltreated individuals also differ from others due to epigenetic modifications and genetic polymorphisms that interact with experience to increase risk for psychopathology. Conclusions-Phenotypic expression of psychopathology may be strongly influenced by exposure to maltreatment leading to a constellation of ecophenotypes. While these ecophenotypes fit within conventional diagnostic boundaries, they likely represent distinct subtypes. Recognition of this distinction may be essential in determining the biological bases of these disorders. Further, treatment guidelines and algorithms may be enhanced if maltreated and non-maltreated individuals with the same diagnostic labels are differentiated. Maltreated children are more likely to suffer psychiatric disorder over the course of their lifetime. In particular, they are more likely to develop major depression (1-5), bipolar disorder (6), anxiety disorders (2, 3, 7), posttraumatic stress disorder (2, 3), substance abuse (2, 8, 9), personality disorders (10, 11) and psychoses (12). Further, it appears that survivors of early maltreatment differ from other individuals with the same psychiatric diagnoses in Disclosures The authors have no conflicts to declare regarding this work. Dr. Teicher has developed and patented technology for the assessment of attention deficit hyperactivity disorder, which has been licensed by McLean Hospital to BioBehavioral Diagnostic Company (BioBDx). Dr. Teicher has received royalty payments, research support, travel and consulting fees from BioBDx. Dr. Teicher has also received, within the last 5 years, research support from CNS Response, Inc. and The Litebook Company, LTD. Dr. Samson has no conflicts to declare.
Research on Child and Adolescent Psychopathology, Oct 4, 2022
with typically developing (TD) individuals (e.g., . These psychopathology symptoms can be trouble... more with typically developing (TD) individuals (e.g., . These psychopathology symptoms can be troublesome and impact functional domains such as academic performances, quality of life, Numerous studies have found that many individuals with Attention-Deficit/Hyperactivity Disorder (ADHD), even those without a comorbid disorder, display heightened levels of internalizing and externalizing symptoms compared Stian Orm
Dissociation, particularly the shutting down of sensory, motor and speech systems, has been propo... more 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.
Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punis... more Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse.
Background: Individuals who were maltreated during childhood are faced with increased risks for d... more Background: Individuals who were maltreated during childhood are faced with increased risks for developing various psychological symptoms that are particularly resistant to traditional treatments. This pilot study investigated the effects of a mindfulness based behavioral intervention for young adults with a childhood maltreatment history. Methods: This study looked at self-report psychological questionnaires from 20 subjects (5 males) before and after a mindfulness-based behavioral intervention, compared to 18 subjects (6 males) in the waiting list control group (age range 22-29); all subjects experienced mild-to-moderate childhood maltreatment. We analyzed changes in stress, anxiety, depression, mindfulness and self-compassion related to the intervention with linear mixed effects models; we also analyzed the relationships among questionnaire score changes with partial correlation analyses and mediation analysis. Results: Linear mixed effects model analyses revealed significant group by time interaction on stress (p < 0.01), anxiety (p < 0.05), and self-compassion (p < 0.01), with the mindfulness group having significant reduction in stress and anxiety (p < 0.01), and significant increase in mindfulness (p < 0.05) and self-compassion (p < 0.001). Partial correlation analyses showed that among all subjects from both groups, changes in mindfulness positively correlated with changes in self-compassion (r = 0.578, p = 0.001), which negatively correlated with changes in depression (r = -0.374, p = 0.05) and anxiety (r = -0.395, p < 0.05). Changes in self-compassion mediated, in part, the relationship between changes in mindfulness and changes in anxiety (average causal mediation effect = -4.721, p < 0.05). We observed a dose-dependent effect of the treatment, i.e., the number of intervention sessions attended were negatively correlated with changes in stress (r = -0.674, p < 0.01), anxiety (r = -0.580, p < 0.01), and
Objective-Depression is the most common adult outcome of exposure to childhood sexual abuse (CSA)... more Objective-Depression is the most common adult outcome of exposure to childhood sexual abuse (CSA). In this study, we retrospectively assessed the length of time from initial abuse exposure to onset of a major depressive episode. Method-A community-based survey of childhood experiences in 564 young adults (ages 18 to 22 years) conducted between 1997 and 2001 identified 29 right-handed female subjects with CSA but no other exposure to trauma. Subjects were interviewed for lifetime history and age of onset of Axis I disorders using the Structured Clinical Interview for DSM-IV Axis I Disorders. Results-Sixty-two percent (n = 18) of the sexual abuse sample met full lifetime criteria for major depression. Episodes of depression emerged, on average, 9.2 ± 3.6 years after onset of exposure to sexual abuse. Mean survival time from onset of abuse to onset of depression for the entire sample was 11.47 years (95% CI: 9.80 -13.13 years). There was a surge in new cases between 12-15 years of age. Average time to onset of posttraumatic stress disorder was 8.0 ± 3.9 years. Conclusions-Exposure to CSA appears to sensitize women to the development of depression, and to shift age of onset to early adolescence. Findings from this formative study suggest that clinicians should not interpret the absence of symptoms at the time of CSA as a sign of resilience. Continued monitoring of victims of CSA as they pass through puberty is recommended. Reasons for the time lag between CSA and depression are proposed along with potential strategies for early intervention.
The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models h... more The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17M/35F, 25.4 ±3.1 years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10-11 years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose-response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range 11 -54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure
Journal of Child Psychology and Psychiatry, Feb 1, 2016
Background and Scope-Childhood maltreatment is the most important preventable cause of psychopath... more Background and Scope-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. 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. Findings-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. 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. Conclusion-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 increases risk for mood, anxiety, substance use and personality disorders ... more Childhood maltreatment increases risk for mood, anxiety, substance use and personality disorders and is associated with alterations in structure, function and connectivity of brain regions involved in emotional regulation. We sought to assess whether maltreatment was specifically associated with disturbances in positive or negative mood regulation. Ecological momentary ratings were collected with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six times per day over a week in 60 unmedicated participants (22 control, 38 maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a history of major depression but all were currently euthymic. Principal component analysis with varimax rotation was used to provide orthogonal measures of positive and negative valence, which were analyzed for indices of variability,
Journal of Child and Adolescent Psychopharmacology, Jun 1, 2008
Background and purpose: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent dis... more Background and purpose: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder that can respond dramatically to medication, if dose is appropriately titrated. Studies suggest that computer measures of attention cannot be used for titration as they show improvement on doses too low to produce clinical benefits. We assessed whether measures of motor activity and attention using the McLean Motion Attention Test (M-MAT™) could identify doses associated with optimal clinical response. Methods: Eleven boys (9.6 Ϯ 1.8 years), receiving treatment with methylphenidate, and meeting DSM-IV criteria for ADHD, participated in this triple-blind (parent, child, rater), within-subject, efficacy study. Subjects received 1 week each of placebo, low (0.4 mg/kg), medium (0.8 mg/kg), and high (1.5 mg/kg) daily doses of methylphenidate. Parents rated response using an index of clinical global improvement. Results: In 9/11 subjects, the dose that produced the best improvement on M-MAT™ measures was also the dose that produced the best clinical outcome (p Ͻ 10 Ϫ5 ). Parents rated response to this dose significantly better than response to previously prescribed treatment. Objective measures of primarily activity and secondarily attention responded to treatment in a manner concordant with clinical ratings, suggesting that these measures have ecological validity, and the potential to facilitate medication management and titration.
Background-Although the literature suggests that childhood maltreatment (CM) relates to adolescen... more Background-Although the literature suggests that childhood maltreatment (CM) relates to adolescent heavy episodic drinking (HED), few studies have examined the long-term effects of CM on adolescent HED. This study is the first to examine associations between exposure to CM and trajectories of HED from adolescence to young adulthood for the US population. Methods-Four waves of data from the National Longitudinal Study of Adolescent Health were used. A total of 8,503 adolescents followed from adolescence (7th-12th grades) into young adulthood (ages 24-32) were assessed on CM and past-year HED frequency. Using growth curve modeling, trajectories of adolescent HED were examined, with subtype, frequency, and severity of CM as the primary independent variables. All of our analyses controlled for common risk factors for adolescent HED, including demographics, parental and peer alcohol use, parental education and employment, family income, parent-child relationship, and adolescent depression. Results-After controlling for potential risk factors, neglect and physical abuse -both individually and in conjunction -were associated with faster increases in HED during adolescence and persistently elevated HED over much of adolescence and young adulthood. The frequency of neglect and physical abuse -individually and in conjunction -was also associated with the trajectory of HED, such that additional instances of these types of maltreatment were associated with faster increases in HED during adolescence and higher rates of peak use during young adulthood.
Zeitschrift Fur Klinische Psychologie Und Psychotherapie, Apr 1, 2014
Background: Adverse childhood experiences increase the risk of psychopathology and influence seve... more Background: Adverse childhood experiences increase the risk of psychopathology and influence severity of mental ill-health as well as treatment outcomes. Clinical psychological work requires validated instruments to comprehensively assess childhood adversities. Objective: This paper deals with the construction and psychometric evaluation of the German version of the modified "Adverse Childhood Experience" Index, called "Belastende Kindheitserfahrungen" (KERF). This instrument assesses childhood adversity in depth. Method: Based on interview data of 165 female subjects, ten subscales were modeled using Rasch-Models. Correlations with the CTQ (Childhood Trauma Questionnaire) and psychopathology were analyzed. Results: Subscales were modeled, with the support of conceptual approaches. Satisfying associations with the CTQ and psychopathology were found. Conclusions: KERF enables a valid and detailed assessment of childhood adversities.
Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans... more Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans, the amygdala develops rapidly during the first two years of life. Thus, disturbed care during this period may be particularly important to amygdala development. In the context of a 30-year longitudinal study of impoverished, highly stressed families, we assessed whether disorganization of the attachment relationship in infancy was related to amygdala volume in adulthood. Amygdala volumes were assessed among 18 low-income young adults (8M/10F, 29.33±0.49 years) first observed in infancy (8.5±5.6 months) and followed longitudinally to age 29. In infancy (18.58±1.02 mos), both disorganized infant attachment behavior and disrupted maternal communication were assessed in the standard Strange Situation Procedure (SSP). Increased left amygdala volume in adulthood was associated with both maternal and infant components of disorganized attachment interactions at 18 months of age (overall r = .679, p < .004). Later stressors, including childhood maltreatment and attachment disturbance in adolescence, were not significantly related to left amygdala volume. Left amygdala volume was further associated with dissociation and limbic irritability in adulthood. Finally, left amygdala volume mediated the prediction from attachment disturbance in infancy to limbic irritability in adulthood. Results point to the likely importance of quality of early care for amygdala development in human children as well as in rodents. The long-term prediction found here suggests that the first two years of life may be an early sensitive period for amygdala development during which clinical intervention could have particularly important consequences for later child outcomes.
Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for... more Previous studies have reported cerebellar abnormalities or static ataxia associated with risk for chronic use of alcohol and drugs. Adverse childhood experience (ACE) is another strong risk factor for later substance abuse. We therefore, sought to ascertain the relationship between morphological phenotypes of the lingula (Lobule I) of the anterior cerebellar vermis (ACV), and exposure to emotional (EM) versus physical (PM) maltreatment,on the degree of ongoing alcohol or drug use. The study design consisted of a cross-sectional in vivo neuroimaging study, utilizing retrospective assessment of maltreatment history and self-reports of alcohol and substance use. Study participants were 153 subjects (54M/99F, 21.9±2.2 years) selected for imaging from a database of 1,402 community participants 18-25 years of age, who completed a detailed online screening instrument, and met rigorous inclusion/exclusion criteria. Subjects were exposed to only physical abuse or harsh corporal punishment (PM group, n=37); parental verbal abuse and/or witnessing domestic violence (EM group, n= 58); or had no history of maltreatment or Axis I disorders (n=58). The main outcomes measures consisted of the grey matter volume of Lobule I as measured by manual tracing, number and type of alcoholic beverages consumed during a drinking session, number of sessions per month, and monthly drug use, along with family history of drug and alcohol abuse. Lingula thickness was not attenuated by alcohol use or maltreatment history. However, increased lingula thickness was associated with greater consumption of drugs and hard liquor, particularly in physically maltreated subjects who consumed 2.5-and 2.7-fold more alcohol, and used drugs 6.1-and 7.8-fold more frequently than controls or EM subjects, respectively. In conclusion, physical maltreatment was observed to interact with cerebellar morphology resulting in a strong association with alcohol and substance use. Lingula thickness may represent a novel, experientially-sensitive, phenotypic risk factor for enhanced alcohol and drug use, that perhaps modulates sensitivity to these agents.
Child and Adolescent Psychiatry and Mental Health, Mar 4, 2023
Background Exposure to potentially traumatic experiences (PTEs) is common among children and adol... more Background Exposure to potentially traumatic experiences (PTEs) is common among children and adolescents, but relatively little is known about the epidemiology of trauma and trauma-related psychopathology in children and youth. The present cross-sectional epidemiological study aimed to explore factors that is associated with posttraumatic stress symptoms (PTSS) in children. Method Data stem from the Bergen Child Study, a series of cross-sectional multi-phase surveys of children born between 1993 and 1995 in Bergen, Norway. The sample used is from the second wave of the Bergen Child Study (BCS) conducted in 2006, a two-phase study. The study entailed a detailed psychiatric evaluation using the Development and well-being assessment (DAWBA). The DAWBA was administered to parents or caregivers and covered diagnostic areas, child and family background, and child strengths. A total of 2043 parents participated. Out of the total sample, parents reported that 4.8% children had experienced PTEs at some point in their lives. The findings revealed current PTSS in 30.9% of children exposed to PTE, which was 1.5% of the total sample. None of the parents reported PTSS in their children over the threshold for diagnosing posttraumatic stress disorder (PTSD). The most common PTSS cluster was arousal reactivity (90.0%), followed by negative cognitions and mood (80%). The least frequent symptom cluster was intrusions (63.3%) and avoidance (60%). Children with PTSS were reported to live in families with significantly more family stressors (p = 0.001, d = 0.8) and had utilized significantly more sources for help relative to those without PTSS (p = 0.001, d = 0.75). The present population study on children revealed a lower prevalence rate of PTEs and PTSD than previous studies. It provided findings in the field of trauma on parent-reported PTSS and PTSD symptom clusters not restricted to the clinical level of PTSD. Lastly, it highlighted how family-life stressors and support differed between those who had PTSS and those with no PTSS.
Background-Childhood abuse is a major risk factor for psychopathology. Previous studies have iden... more Background-Childhood abuse is a major risk factor for psychopathology. Previous studies have identified brain differences in maltreated individuals but have not focused on potential differences in network architecture. Methods-High-resolution T1-weighted MRI scans were obtained from 265 unmedicated, righthanded 18-25-year-olds who were classified as maltreated (n=142, 55M/87F) or non-maltreated (n=123, 46M/77F) based on extensive interviews. Cortical thickness was assessed in 112 cortical regions (nodes) and inter-regional partial correlations across subjects were calculated to derive the lowest equivalent cost single-cluster group networks. Permutation tests were used to ascertain whether maltreatment was associated with significant alterations in key centrality measures of these regions and membership in the highly interconnected 'rich club'. Results-Marked differences in centrality (connectedness, 'importance') were observed in a handful of cortical regions. Left anterior cingulate had the second highest number of connections (degree centrality) and was a component of the 'rich club' in the control network but ranked low in connectedness (106 th of 112 nodes) in the network derived from maltreated-subjects (p<0.01). Conversely, right precuneus and right anterior insula ranked first and 15 th in degree centrality in the maltreated network versus 90 th (p=0.01) and 105 th (p<0.03) in the control network. Conclusions-Maltreatment was associated with decreased centrality in regions involved in emotional regulation and ability to accurately attribute thoughts or intentions to others and with enhanced centrality in regions involved in internal emotional perception, self-referential thinking and self-awareness. This may provide a potential mechanism for how maltreatment increases risk for psychopathology.
Six depressed patients free of recent serious suicidal ideation developed intense, violent suicid... more Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupa tion after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these pa tients had ever experienced a similar state during treat-• ment with any other psychotropic drug.
Severe early stress and maltreatment produces a cascade of events that have the potential to alte... more Severe early stress and maltreatment produces a cascade of events that have the potential to alter brain development. The first stage of the cascade involves the stress-induced programming of the glucocorticoid, noradrenergic, and vasopressin-oxytocin stress response systems to augment stress responses. These neurohumors then produce effects on neurogenesis, synaptic overproduction and pruning, and myelination during specific sensitive periods. Major consequences include reduced size of the mid-portions of the corpus callosum; attenuated development of the left neocortex, hippocampus, and amygdala along with abnormal frontotemporal electrical activity; and reduced functional activity of the cerebellar vermis. These alterations, in turn, provide the neurobiological framework through which early abuse increases the risk of developing post-traumatic stress disorder (PTSD), depression, symptoms of attention-deficit/hyperactivity, borderline personality disorder, dissociative identity disorder, and substance abuse.
Objective-Childhood maltreatment increases risk for psychopathology. For some highly prevalent di... more Objective-Childhood maltreatment increases risk for psychopathology. For some highly prevalent disorders (i.e., major depression, substance abuse, anxiety disorders and posttraumatic stress disorder) there is a substantial subset of individuals with maltreatment histories and a substantial subset without. Do those with maltreatment histories represent a clinically and biologically distinct subtype? Method-The authors review literature on maltreatment as a risk factor for these disorders and on the clinical differences between individuals with and without maltreatment who share the same diagnoses. Neurobiological findings in maltreated individuals are reviewed and compared to findings reported for these disorders. Results-Maltreated individuals with depressive, anxiety and substance use disorders show an earlier age of onset, greater symptom severity, more comorbidity, increased risk for suicide and poorer treatment response than non-maltreated individuals with the same diagnoses. Imaging findings associated with these disorders, such as reduced hippocampal volume and amygdala hyperreactivity are more consistently observed in maltreated individuals and may represent a maltreatment-related risk factor. Maltreated individuals also differ from others due to epigenetic modifications and genetic polymorphisms that interact with experience to increase risk for psychopathology. Conclusions-Phenotypic expression of psychopathology may be strongly influenced by exposure to maltreatment leading to a constellation of ecophenotypes. While these ecophenotypes fit within conventional diagnostic boundaries, they likely represent distinct subtypes. Recognition of this distinction may be essential in determining the biological bases of these disorders. Further, treatment guidelines and algorithms may be enhanced if maltreated and non-maltreated individuals with the same diagnostic labels are differentiated. Maltreated children are more likely to suffer psychiatric disorder over the course of their lifetime. In particular, they are more likely to develop major depression (1-5), bipolar disorder (6), anxiety disorders (2, 3, 7), posttraumatic stress disorder (2, 3), substance abuse (2, 8, 9), personality disorders (10, 11) and psychoses (12). Further, it appears that survivors of early maltreatment differ from other individuals with the same psychiatric diagnoses in Disclosures The authors have no conflicts to declare regarding this work. Dr. Teicher has developed and patented technology for the assessment of attention deficit hyperactivity disorder, which has been licensed by McLean Hospital to BioBehavioral Diagnostic Company (BioBDx). Dr. Teicher has received royalty payments, research support, travel and consulting fees from BioBDx. Dr. Teicher has also received, within the last 5 years, research support from CNS Response, Inc. and The Litebook Company, LTD. Dr. Samson has no conflicts to declare.
Research on Child and Adolescent Psychopathology, Oct 4, 2022
with typically developing (TD) individuals (e.g., . These psychopathology symptoms can be trouble... more with typically developing (TD) individuals (e.g., . These psychopathology symptoms can be troublesome and impact functional domains such as academic performances, quality of life, Numerous studies have found that many individuals with Attention-Deficit/Hyperactivity Disorder (ADHD), even those without a comorbid disorder, display heightened levels of internalizing and externalizing symptoms compared Stian Orm
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