Potential sensitive period effects of maltreatment on amygdala, hippocampal and cortical response to threat.

Childhood maltreatment is a leading risk factor for psychopathology, though it is unclear why some develop risk averse disorders, such as anxiety and depression, and others risk-taking disorders including substance abuse. A critical question is whether the consequences of maltreatment depend on the number of different types of maltreatment experienced at any time during childhood or whether there are sensitive periods when exposure to particular types of maltreatment at specific ages exert maximal effects. Retrospective information on severity of exposure to ten types of maltreatment during each year of childhood was collected using the Maltreatment and Abuse Chronology of Exposure scale. Artificial Intelligence predictive analytics were used to delineate the most important type/time risk factors. BOLD activation fMRI response to threatening versus neutral facial images was assessed in key components of the threat detection system (i.e., amygdala, hippocampus, anterior cingulate, inferior frontal gyrus and ventromedial and dorsomedial prefrontal cortices) in 202 healthy, unmedicated, participants (84 M/118 F, 23.2 ± 1.7 years old). Emotional maltreatment during teenage years was associated with hyperactive response to threat whereas early childhood exposure, primarily to witnessing violence and peer physical bullying, was associated with an opposite pattern of greater activation to neutral than fearful faces in all regions. These findings strongly suggest that corticolimbic regions have two different sensitive period windows of enhanced plasticity when maltreatment can exert opposite effects on function. Maltreatment needs to be viewed from a developmental perspective in order to fully comprehend its enduring neurobiological and clinical consequences.

Practitioner Review: Neurobiological consequences of childhood maltreatment - clinical and therapeutic implications for practitioners.

BACKGROUND: Childhood maltreatment is one of the most important preventable risk factors for a wide variety of psychiatric disorders. Further, when psychiatric disorders emerge in maltreated individuals they typically do so at younger ages, with greater severity, more psychiatric comorbid conditions, and poorer response to established treatments, resulting in a more pernicious course with an increased risk for suicide. Practitioners treating children, adolescents, and young adults with psychiatric disorders will likely encounter the highest prevalence of clients with early-onset maltreatment-associated psychiatric disorders. These may be some of their most challenging cases. METHOD: In this report, we explore key validated alterations in brain structure, function, and connectivity associated with exposure to childhood maltreatment as potential mechanisms behind their patients' clinical presentations. RESULTS: We then summarize key behavioral presentations likely associated with neurobiological alterations and propose a toolkit of established trauma and skills-based strategies that may help diminish symptoms and foster recovery. We also discuss how some of these alterations may serve as latent vulnerability factors for the possible development of future psychopathology. CONCLUSIONS: Research on the neurobiological consequences of childhood adversity provides a vastly enriched biopsychosocial understanding of the developmental origins of health and pathology that will hopefully lead to fundamental advances in clinical psychology and psychiatry.

The neurobiological effects of childhood maltreatment on brain structure, function, and attachment.

Childhood maltreatment is a risk factor for psychopathologies, and influences brain development at specific periods, particularly during early childhood and adolescence. This narrative review addresses phenotypic alterations in sensory systems associated with specific types of childhood maltreatment exposure, periods of vulnerability to the neurobiological effects of maltreatment, and the relationships between childhood maltreatment and brain structure, function, connectivity, and network architecture; psychopathology; and resilience. It also addresses neurobiological alterations associated with maternal communication and attachment disturbances, and uses laboratory-based measures during infancy and case-control studies to elucidate neurobiological alterations in reactive attachment disorders in children with maltreatment histories. Moreover, we review studies on the acute effects of oxytocin on reactive attachment disorder and maltreatment and methylation of oxytocin regulatory genes. Epigenetic changes may play a critical role in initiating or producing the atypical structural and functional brain alterations associated with childhood maltreatment. However, these changes could be reversed through psychological and pharmacological interventions, and by anticipating or preventing the emergence of brain alterations and subsequent psychopathological risks.

Using Norwegian National Patient Registry data to understand associations between potentially traumatic life experiences and mental health care use in adolescence.

Exposure to potentially traumatic experiences (PTEs) is common among children and adolescents and associated with an increased risk of psychiatric diagnoses. This study aimed to ascertain how the number of PTEs differed across adolescent psychiatric diagnoses. Data on PTE exposure were derived from the youth@hordaland survey, and Axis 1 data were from the linked Norwegian National Patient Registry (NPR). Among 10,257 total adolescents, 9,555 (age range: 16-19 years, 53.9% female) consented to register linkage, 8,845 of whom were included in the analyses. Having contact with Child and Adolescent Mental Health Services (CAMHS) predicted more PTEs (estimated marginal mean [EMM] = 1.04, SE = 0.05) and exposure to two or more PTEs compared to having no CAMHS contact (EMM = 0.60) after adjusting for age, ethnicity, sex, and parental education. Adolescents diagnosed with attention-deficit/hyperactivity disorder, depression, trauma-related disorders, conduct disorder, and anxiety experienced significantly more PTEs (EMMs = 0.90-1.63) than those with no CAMHS contact (EMM = 0.57, SE = 0.01). All diagnostic categories except psychosis, autism spectrum disorders, and eating disorders had a significantly higher rate of PTEs compared with adolescents with no CAMHS contact. The study highlights the potential role of exposure to multiple PTEs as a transdiagnostic risk factor, although the level of risk varies between diagnoses.

Associations Between Distinct Trauma Classes and Mental Health Care Utilization in Norwegian Adolescents: A National Registry Study.

Adolescents who experience potentially traumatic experiences (PTEs) have an increased risk of psychopathology. PTEs often co-occur and may form interrelated patterns of exposure. This study investigated underlying classes of PTE exposure among Norwegian adolescent participants in the youth@hordaland study, and whether such classes were associated with contact with child and adolescent mental health services (CAMHS) and psychiatric diagnoses. The data stem from the population-based youth@hordaland study conducted in 2012 which was linked to the Norwegian Patient Registry (NPR, n = 8845). Exposure to PTEs was assessed by adolescent self-report whereas psychiatric disorders (Axis 1) were derived from the NPR. Latent Class Analysis was used to identify distinct classes of PTE exposure-patterns in the data. Logistic regression analyses were performed to investigate associations between classes of PTEs and contact with CAMHS and psychiatric diagnoses. Three classes of PTE exposure were identified based on model fit indices and theoretical considerations. Compared with participants in the low trauma class (88% of participants), those in the Situational-(6%) and Interpersonal trauma class (6%) had higher odds-ratios (ORs) for contact with CAMHS (OR = 2.27 (95% CI [1.78, 2.87])) and (OR = 3.26 (95% CI [2.61, 4.04])) respectively, and for being diagnosed with a psychiatric disorder in CAMHS (ORs ranged from 2.19 - 10.4) after adjusting for sex and parental education. There were more participants diagnosed with ADHD within the Interpersonal trauma class compared to the Situational trauma class when adjusting for sex and parental education (OR = 2.22 (95% CI [1.17, 4.40])). Three relatively homogeneous PTE classes, consisting of distinct patterns of trauma exposure were associated with a higher odds of contact with CAMHS and of being diagnosed with a psychiatric disorder in CAMHS. The study highlights the co-occurrence of PTEs and their impact across the diagnostic spectrum.

Negative versus withdrawn maternal behavior: Differential associations with infant gray and white matter during the first 2 years of life.

Distinct neural effects of threat versus deprivation emerge by childhood, but little data are available in infancy. Withdrawn versus negative parenting may represent dimensionalized indices of early deprivation versus early threat, but no studies have assessed neural correlates of withdrawn versus negative parenting in infancy. The objective of this study was to separately assess the links of maternal withdrawal and maternal negative/inappropriate interaction with infant gray matter volume (GMV), white matter volume (WMV), amygdala, and hippocampal volume. Participants included 57 mother-infant dyads. Withdrawn and negative/inappropriate aspects of maternal behavior were coded from the Still-Face Paradigm at four months infant age. Between 4 and 24 months (M age = 12.28 months, SD = 5.99), during natural sleep, infants completed an MRI using a 3.0 T Siemens scanner. GMV, WMV, amygdala, and hippocampal volumes were extracted via automated segmentation. Diffusion weighted imaging volumetric data were also generated for major white matter tracts. Maternal withdrawal was associated with lower infant GMV. Negative/inappropriate interaction was associated with lower overall WMV. Age did not moderate these effects. Maternal withdrawal was further associated with reduced right hippocampal volume at older ages. Exploratory analyses of white matter tracts found that negative/inappropriate maternal behavior was specifically associated with reduced volume in the ventral language network. Results suggest that quality of day-to-day parenting is related to infant brain volumes during the first two years of life, with distinct aspects of interaction associated with distinct neural effects.

Recognizing the importance of childhood maltreatment as a critical factor in psychiatric diagnoses, treatment, research, prevention, and education.

Childhood maltreatment is the most important preventable risk factor for psychiatric disorders. Maltreated individuals typically develop psychiatric disorders at an earlier age, have a more pernicious course, more comorbidities, greater symptom severity, and respond less favorably to treatments than non-maltreated individuals with the same primary DSM-5 diagnosis. Furthermore, maltreated individuals have alterations in stress-susceptible brain regions, hypothalamic-pituitary-adrenal response, and inflammatory marker levels not discernible in their non-maltreated counterparts. Hence, maltreated and non-maltreated individuals with the same primary DSM-5 diagnoses appear to be clinically and neurobiologically distinct. The failure to embody this distinction in DSM-5 has interfered with our ability to discover novel treatments, to recommend currently available treatments most likely to be efficacious, and has been a largely unrecognized confound that has thwarted our ability to identify the biological basis for major psychiatric disorders. Incorporating this distinction into DSM will help transform this sign and symptom-based classification system to a more etiologically informed nosology. We discuss several diagnostic alternatives and recommend the inclusion of a Developmental Trauma Disorder diagnosis for severely dysregulated individuals, of all ages, with numerous comorbidities, who experienced interpersonal victimization and disruptions in attachment, such as emotional maltreatment or neglect. For less severely affected maltreated individuals, we suggest using conventional diagnostic categories, such as major depression, but with an essential modifier indicating a history of childhood maltreatment, or early life stress, to delineate the ecophenotypic variant. Implementing this strategy should improve our ability to effectively diagnose and treat individuals with psychiatric disorders and to accelerate discovery.

The effects of childhood maltreatment on brain structure, function and connectivity.

Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

Differential effects of childhood neglect and abuse during sensitive exposure periods on male and female hippocampus.

The hippocampus is a highly stress susceptible structure and hippocampal abnormalities have been reported in a host of psychiatric disorders including major depression and post-traumatic stress disorder (PTSD). The hippocampus appears to be particularly susceptible to early life stress with a graded reduction in volume based on number of types (multiplicity) or severity of maltreatment. We assessed whether the most important predictors of adult hippocampal volume were multiplicity, severity or duration of exposure or timing of maltreatment during developmental sensitive periods. 3T MRIs were collected on 336 unmedicated, right-handed subjects (132M/204F, 18-25 years). Exposure to broad categories of abuse and neglect during each year of childhood were assessed using the Maltreatment and Abuse Chronology of Exposure scale and evaluated using artificial intelligence and predictive analytics. Male hippocampal volume was predicted by neglect, but not abuse, up through 7 years of age. Female hippocampal volume was predicted by abuse, but not neglect, at 10, 11, 15 and 16 years. Exposure at peak age had greater predictive importance than multiplicity, severity or duration. There were also marked gender differences in subfields and portions (head, body or tail) affected by exposure. History and symptoms of major depression, PTSD or anxiety disorders were not predictive of hippocampal volume once maltreatment was accounted for. Neglect appears to foster inadequate hippocampal development in males while abuse appears to produce a stress-related deficit in females. Studies assessing hippocampal volume in psychiatric disorders need to control for the gender-specific effects of abuse and neglect.

Childhood trauma and the enduring consequences of forcibly separating children from parents at the United States border.

Forcible separation and detention of children from parents seeking asylum in the United States has been decried as immoral and halted by court order. Babies and children have been separated and transported to facilities sometimes many miles away. Limited data on forced detention of unaccompanied minors reveal high incidence of posttraumatic stress, anxiety disorders, depression, aggression, and suicidal ideation. These consequences will be magnified in youths forcibly separated from their parents, particularly younger children who depend on attachment bonds for self-regulation and resilience. Studies exploring the neuropsychiatric consequences of traumatic stress have revealed consistent effects of early life stress on brain structure, function and connectivity, and the identification of sensitive periods, which occur throughout childhood when specific regions and pathways are strongly influenced by adversity. Studies of epigenetics, inflammation and allostatic load are similarly enhancing our awareness of the molecular mechanisms underpinning the long-term consequences of traumatic stress. We must consider effects on the developing brain, mind and body to appreciate the long-term consequences of policies that force separation and detention of children.

Childhood maltreatment is associated with alteration in global network fiber-tract architecture independent of history of depression and anxiety.

Childhood maltreatment is a major risk factor for psychopathology. It is also associated with alterations in the network architecture of the brain, which we hypothesized may play a significant role in the development of psychopathology. In this study, we analyzed the global network architecture of physically healthy unmedicated 18-25 year old subjects (n=262) using diffusion tensor imaging (DTI) MRI and tractography. Anatomical networks were constructed from fiber streams interconnecting 90 cortical or subcortical regions for subjects with no-to-low (n=122) versus moderate-to-high (n=140) exposure to maltreatment. Graph theory analysis revealed lower degree, strength, global efficiency, and maximum Laplacian spectra, higher pathlength, small-worldness and Laplacian skewness, and less deviation from artificial networks in subjects with moderate-to-high exposure to maltreatment. On balance, local clustering was similar in both groups, but the different clusters were more strongly interconnected in the no-to-low exposure group. History of major depression, anxiety and attention deficit hyperactivity disorder did not have a significant impact on global network measures over and above the effect of maltreatment. Maltreatment is an important factor that needs to be taken into account in studies examining the relationship between network differences and psychopathology.

Annual Research Review: Enduring neurobiological effects of childhood abuse and neglect.

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.

Actigraph measures discriminate pediatric bipolar disorder from attention-deficit/hyperactivity disorder and typically developing controls.

BACKGROUND: Distinguishing pediatric bipolar disorder (BD) from attention-deficit hyperactivity disorder (ADHD) can be challenging. Hyperactivity is a core feature of both disorders, but severely disturbed sleep and circadian dysregulation are more characteristic of BD, at least in adults. We tested the hypothesis that objective measures of activity, sleep, and circadian rhythms would help differentiate pediatric subjects with BD from ADHD and typically developing controls. METHODS: Unmedicated youths (N = 155, 97 males, age 5-18) were diagnosed using DSM-IV criteria with Kiddie-SADS PL/E. BD youths (n = 48) were compared to typically developing controls (n = 42) and children with ADHD (n = 44) or ADHD plus comorbid depressive disorders (n = 21). Three-to-five days of minute-to-minute belt-worn actigraph data (Ambulatory Monitoring Inc.), collected during the school week, were processed to yield 28 metrics per subject, and assessed for group differences with analysis of covariance. Cross-validated machine learning algorithms were used to determine the predictive accuracy of a four-parameter model, with measures reflecting sleep, hyperactivity, and circadian dysregulation, plus Indic's bipolar vulnerability index (VI). RESULTS: There were prominent group differences in several activity measures, notably mean 5 lowest hours of activity, skewness of diurnal activity, relative circadian amplitude, and VI. A predictive support vector machine model discriminated bipolar from non-bipolar with mean accuracy of 83.1 ± 5.4%, ROC area of 0.781 ± 0.071, kappa of 0.587 ± 0.136, specificity of 91.7 ± 5.3%, and sensitivity of 64.4 ± 13.6%. CONCLUSIONS: Objective measures of sleep, circadian rhythmicity, and hyperactivity were abnormal in BD. Wearable sensor technology may provide bio-behavioral markers that can help differentiate children with BD from ADHD and healthy controls.

Type and timing of adverse childhood experiences differentially affect severity of PTSD, dissociative and depressive symptoms in adult inpatients.

BACKGROUND: A dose-dependent effect of Adverse Childhood Experiences (ACE) on the course and severity of psychiatric disorders has been frequently reported. Recent evidence indicates additional impact of type and timing of distinct ACE on symptom severity experienced in adulthood, in support of stress-sensitive periods in (brain) development. The present study seeks to clarify the impact of ACE on symptoms that are often comorbid across various diagnostic groups: symptoms of posttraumatic stress disorder (PTSD), shutdown dissociation and depression. A key aim was to determine and compare the importance of dose-dependent versus type and timing specific prediction of ACE on symptom levels. METHODS: Exposure to ten types of maltreatment up to age 18 were retrospectively assessed in N = 129 psychiatric inpatients using the Maltreatment and Abuse Chronology of Exposure (MACE). Symptoms of PTSD, shutdown dissociation, and depression were related to type and timing of ACE. The predictive power of peak types and timings was compared to that of global MACE measures of duration, multiplicity and overall severity. RESULTS: A dose-dependent effect (MACE duration, multiplicity and overall severity) on severity of all symptoms confirmed earlier findings. Conditioned random forest regression verified that PTSD symptoms were best predicted by overall ACE severity, whereas type and timing specific effects showed stronger prediction for symptoms of dissociation and depression. In particular, physical neglect at age 5 and emotional neglect at ages 4-5 were related to increased symptoms of dissociation, whereas the emotional neglect at age 8-9 enhanced symptoms of depression. CONCLUSION: In support of the sensitive period of exposure model, present results indicate augmented vulnerability by type x timing of ACE, in particular emphasizing pre-school (age 4-5) and pre-adolescent (8-9) periods as sensitive for the impact of physical and emotional neglect. PTSD, the most severe stress-related disorder, varies with the amount of adverse experiences irrespective of age of experience. Considering type and timing of ACE improves understanding of vulnerability, and should inform diagnostics of psychopathology like PTSD, dissociation and depression in adult psychiatric patients.

Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum.

Childhood maltreatment or abuse is a major risk factor for mood, anxiety, substance abuse, psychotic, and personality disorders, and it is associated with reduced adult hippocampal volume, particularly on the left side. Translational studies show that the key consequences of stress exposure on the hippocampus are suppression of neurogenesis in the dentate gyrus (DG) and dendritic remodeling in the cornu ammonis (CA), particularly the CA3 subfield. The hypothesis that maltreatment is associated with volume reductions in 3-T MRI subfields containing the DG and CA3 was assessed and made practical by newly released automatic segmentation routines for FreeSurfer. The sample consisted of 193 unmedicated right-handed subjects (38% male, 21.9 ± 2.1 y of age) selected from the community. Maltreatment was quantified using the Adverse Childhood Experience study and Childhood Trauma Questionnaire scores. The strongest associations between maltreatment and volume were observed in the left CA2-CA3 and CA4-DG subfields, and were not mediated by histories of major depression or posttraumatic stress disorder. Comparing subjects with high vs. low scores on the Childhood Trauma Questionnaire and Adverse Childhood Experience study showed an average volume reduction of 6.3% and 6.1% in the left CA2-CA3 and CA4-DG, respectively. Volume reductions in the CA1 and fimbria were 44% and 60% smaller than in the CA2-CA3. Interestingly, maltreatment was associated with 4.2% and 4.3% reductions in the left presubiculum and subiculum, respectively. These findings support the hypothesis that exposure to early stress in humans, as in other animals, affects hippocampal subfield development.

Sensitive periods of amygdala development: the role of maltreatment in preadolescence.

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 that in healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5±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 quartile (MACE-11, ≤3.5). No associations emerged between age of exposure and volume of the left amygdala or bilateral caudate or thalamus. Severity of adversity experienced at age 10-11 contributed to larger right but not left amygdala volume in adulthood. Results provide preliminary evidence that the amygdala may have a developmental sensitive period in preadolescence.

Joint Trajectories of Depression and Rumination: Experiential Predictors and Risk of Nonsuicidal Self-Injury.

OBJECTIVE: Nonsuicidal self-injury (NSSI) is common in adolescence. Rumination is a key risk factor and often co-occurs with depressive symptoms. This is the first study to examine the joint longitudinal trajectories of rumination and depressive symptoms as predictors of NSSI, and the adverse experiences associated with these trajectories. METHOD: A community sample of 1,835 adolescents (55.9% male participants, 12.3 ± 0.5 years of age) completed questionnaires to assess adverse childhood experiences, rumination, depressive symptoms, and NSSI. Assessments were made 4 times over 18 months. RESULTS: A parallel process growth mixture model showed that youth with high trajectories of rumination but low trajectories of depression had moderately increased odds of NSSI (2.43-fold, 95% CI 1.53-3.91) compared with adolescents with low trajectories of both rumination and depression. Odds ratios (ORs) in adolescents with low trajectories of rumination but increasing or high trajectories of depression were similarly elevated, suggesting that high trajectories of rumination or depression were risk factors in isolation. However, odds were 10.06-fold greater (95% CI 5.68-18.02) when high trajectories of rumination occurred in tandem with high trajectories of depression. Multinomial logistic regression showed that male sex (OR 10.54, 95% CI 5.66-19.63), peer victimization (OR 2.25, 95% CI 1.72-2.96), and parental alienation (OR 1.94, 95% CI 1.46-2.57) were key determinants of membership in the highest risk group. CONCLUSION: Risk for NSSI is markedly increased in adolescents with high longitudinal trajectories of depression and rumination. Reducing exposure to peer victimization, cyber victimization, emotional abuse, parental alienation, and interparental conflict may reduce risk.

Beneficial effects of mindfulness-based intervention on hippocampal volumes and episodic memory for childhood adversity survivors.

Background: Adverse Childhood Experience (ACE) has detrimental impacts on neural development, especially hippocampal morphometry. Mindfulness-Based Interventions (MBI) has been shown to induce adaptive hippocampal changes especially at the subiculum. The present study aims to investigate the effects of MBI on subiculum volumes among ACE survivors, as well as the effects on episodic memory as a probe into hippocampal functionality. Methods: We analyzed anatomical MRI data and performance indices from an episodic memory task called the Mnemonic Similarity Task (MST) collected from a randomized controlled longitudinal study that compared an 8-week MBI (N = 20) to an active control condition of Stress Management Education (SME) (N = 19). FreeSurfer 6.0 was used for automated hippocampal subfield segmentation and volumetric estimation. Results: Significant group differences were observed with the volumetric changes of the right whole hippocampus and right subiculum. Only the MBI group showed improved pattern separation capability from MST, which was associated with stress reduction and right subiculum volumetric changes. Limitations: Modest sample size. MST task was performed outside of MRI. Conclusions: These findings suggest beneficial effects of MBI for hippocampal volumes and episodic memory, while highlighting the importance of the subiculum for MBI-induced neural and cognitive changes. The subiculum's known role in inhibitory control was interpreted as a potential mechanism for it to exhibit MBI-induced volumetric changes, which sheds light on the potential neural underpinnings of mindfulness meditation for reducing stress reactivity among ACE survivors.

Childhood adversity severity modulates the associations between adaptive psychological changes and amygdala volumetric changes in response to behavioral interventions.

Background: Adverse Childhood Experience (ACE) has been shown to have detrimental impact on amygdala structure. Prior research found that adaptive psychological changes after Mindfulness-Based Interventions (MBI) were associated with amygdala volumetric changes. The present study aims to further investigate whether such effects also occur among ACE survivors and whether the effects are unique to MBI. Methods: A total of 64 young adult childhood adversity survivors were randomized to an eight-week MBI or Stress Management Education (SME) as an active control condition. Anatomical MRI and questionnaires on mindfulness, stress and psychological health were collected at baseline and post-intervention. Due to subject dropout, the final sample included 39 subjects (MBI:20, SME:19). Results: Both groups showed increased mindfulness levels, reduced stress, and improved psychological symptoms (depression, anxiety, and somatization), with no significant group by time interaction effect. There was no significant group difference on amygdala volumetric changes. Within the MBI group, childhood maltreatment severity was a significant mediator between changes of mindfulness levels and right amygdala volumetric changes. Across pooled sample of both groups, childhood maltreatment was a significant moderator for the effect of trait anxiety level changes on left amygdala volumetric changes. Limitations: Modest sample size, relatively low retention rates, suboptimal monitoring of home practice. Conclusions: MBI did not demonstrate overall better clinical effects than SME. Psychological-change-dependent amygdala volumetric change was not specific to MBI. Childhood maltreatment severity modulated the relationships between adaptive psychological changes and amygdala volumetric changes.

ADHD in girls and boys--gender differences in co-existing symptoms and executive function measures.

BACKGROUND: ADHD is diagnosed and treated more often in males than in females. Research on gender differences suggests that girls may be consistently underidentified and underdiagnosed because of differences in the expression of the disorder among boys and girls. One aim of the present study was to assess in a clinical sample of medication naïve boys and girls with ADHD, whether there were significant gender x diagnosis interactions in co-existing symptom severity and executive function (EF) impairment. The second aim was to delineate specific symptom ratings and measures of EF that were most important in distinguishing ADHD from healthy controls (HC) of the same gender. METHODS: Thirty-seven females with ADHD, 43 males with ADHD, 18 HC females and 32 HC males between 8 and 17 years were included. Co-existing symptoms were assessed with self-report scales and parent ratings. EF was assessed with parent ratings of executive skills in everyday situations (BRIEF), and neuropsychological tests. The three measurement domains (co-existing symptoms, BRIEF, neuropsychological EF tests) were investigated using analysis of variance (ANOVA) and random forest classification. RESULTS: ANOVAs revealed only one significant diagnosis x gender interaction, with higher rates of self-reported anxiety symptoms in females with ADHD. Random forest classification indicated that co-existing symptom ratings was substantially better in distinguishing subjects with ADHD from HC in females (93% accuracy) than in males (86% accuracy). The most important distinguishing variable was self-reported anxiety in females, and parent ratings of rule breaking in males. Parent ratings of EF skills were better in distinguishing subjects with ADHD from HC in males (96% accuracy) than in females (92% accuracy). Neuropsychological EF tests had only a modest ability to categorize subjects as ADHD or HC in males (73% accuracy) and females (79% accuracy). CONCLUSIONS: Our findings emphasize the combination of self-report and parent rating scales for the identification of different comorbid symptom expression in boys and girls already diagnosed with ADHD. Self-report scales may increase awareness of internalizing problems particularly salient in females with ADHD.