Child Behavior Problems and Maltreatment Exposure.

OBJECTIVES: Establish the longitudinal cross-lagged associations between maltreatment exposure and child behavior problems to promote screening and the type and timing of interventions needed. METHODS: The Longitudinal Studies of Child Abuse and Neglect, a multiwave prospective cohort study of maltreatment exposure, enrolled children and caregivers (N = 1354) at approximately age 4 and followed them throughout childhood and adolescence. Families completed 7 waves of data collection with each wave occurring 2 years apart. Maltreatment was confirmed using official case records obtained from Child Protective Services. Six-month frequencies of behavior problems were assessed via caregiver-report. Two random-intercept, cross-lagged panel models tested the directional relations between maltreatment exposure and externalizing and internalizing behaviors. RESULTS: Maltreatment exposure predicted increases in externalizing behaviors at ages 8 (b = 1.06; 95% confidence interval [CI] 0.14-1.98), 12 (b = 1.09; 95% CI 0.08-2.09), and 16 (b = 1.67; 95% CI 0.30-3.05) as well as internalizing behaviors at ages 6 (b = 0.66; 95% CI 0.03-1.29), 12 (b = 1.25; 95% CI 0.33-2.17), and 14 (b = 1.92; 95% CI 0.76-2.91). Increases in externalizing behaviors predicted maltreatment exposure at age 12 (odds ratio 1.02; 95% CI 1.00-1.05). CONCLUSIONS: Maltreatment exposure is robustly associated with subsequent child behavior problems, strengthening inferences about the directionality of these relations. Early screening of externalizing behaviors in pediatric settings can identify children likely to benefit from intervention to reduce such behaviors as well as prevent maltreatment exposure at entry to adolescence.

The influence of pretreatment respiratory sinus arrhythmia dimensions on trauma-focused cognitive behavioral therapy outcomes: Findings from a randomized controlled feasibility trial.

Child maltreatment is associated with respiratory sinus arrhythmia (RSA) dysregulation, a physiological indicator of emotion regulation that predicts elevated posttraumatic stress disorder (PTSD) symptoms and may be a mechanism of action for exposure-based therapies, such as trauma-focused cognitive behavioral therapy (TF-CBT). Animal-assisted therapy (AAT) has been proposed as an adjunct to TF-CBT for improving emotion regulation following maltreatment. The current study reports findings from a randomized controlled feasibility trial (N = 33; Mage = 11.79 years, SD = 3.08; 63.6% White; 66.7% female) that measured youths' resting RSA, RSA reactivity, and RSA recovery in response to a pretreatment laboratory challenge. We tested whether (a) lower pretreatment resting RSA was associated with blunted RSA during the challenge; (b) either of the pretreatment RSA dimensions predicted more severe pretreatment PTSD symptoms; and (c) either of the pretreatment RSA dimensions predicted less severe posttreatment PTSD symptoms and, as an exploratory aim, whether this was moderated by treatment group (i.e., TF-CBT vs. TF-CBT + AAT). Results from multiple linear regression indicated that, after controlling for pretreatment symptom severity, there was a large effect size for higher resting RSA predicting less severe caregiver-reported posttreatment PTSD symptoms, ß = -.52, p = .058, and higher RSA during recovery predicting less severe child-reported posttreatment PTSD symptoms, ß = -.70, p = .056, although these findings were not significant. These preliminary results offer important insights for future studies to investigate how the ability to regulate RSA informs which children need additional support to benefit from psychotherapeutic treatment.

The Impact of Time Since Menarche for Depressive and Anxiety Symptom Severity in Adolescence and Young Adulthood.

PURPOSE: The study mapped depressive and anxiety symptom trajectories throughout adolescence and early adulthood, arrayed by time since menarche, a novel indicator of pubertal change and examined the effect of age of menarche and pubertal timing, more frequently used variables, on depressive and anxiety symptom severity trajectories. METHODS: Secondary analysis of a cross-sequential prospective longitudinal investigation included a community sample of 262 US, adolescent females. Participants were enrolled in age cohorts of 11, 13, 15, and 17 years. Four annual waves of data were collected. Self-report of age at menarche was categorized into pubertal timing categories. A novel measure "time since menarche" (chronological age at each wave minus age at menarche), was measured along with depressive and anxiety symptom severity. Two-piece growth curve modeling with landmark registration examined depressive and anxiety symptom severity trajectories according to time since menarche. RESULTS: There was no change (p > .05) in depression and anxiety symptom severity before menarche; however, in the years leading away from menarche, depression and anxiety symptom severity decreased (p < .05). Age at menarche was not associated with change in depressive and anxiety symptom severity (p > .05) and there were no moderating effects of pubertal timing. DISCUSSION: Depressive and anxiety symptoms decrease in the years leading away from menarche, suggesting puberty-related psychopathology may be transitory in some individuals. Time since menarche may be a clinically relevant indicator of psychological functioning in pubescent adolescent females. Future studies should examine this variable in larger samples, including more adolescents in the earlier stages of puberty.

Contamination bias in the estimation of child maltreatment causal effects on adolescent internalizing and externalizing behavior problems.

BACKGROUND: When unaddressed, contamination in child maltreatment research, in which some proportion of children recruited for a nonmaltreated comparison group are exposed to maltreatment, downwardly biases the significance and magnitude of effect size estimates. This study extends previous contamination research by investigating how a dual-measurement strategy of detecting and controlling contamination impacts causal effect size estimates of child behavior problems. METHODS: This study included 634 children from the LONGSCAN study with 63 cases of confirmed child maltreatment after age 8 and 571 cases without confirmed child maltreatment. Confirmed child maltreatment and internalizing and externalizing behaviors were recorded every 2 years between ages 4 and 16. Contamination in the nonmaltreated comparison group was identified and controlled by either a prospective self-report assessment at ages 12, 14, and 16 or by a one-time retrospective self-report assessment at age 18. Synthetic control methods were used to establish causal effects and quantify the impact of contamination when it was not controlled, when it was controlled for by prospective self-reports, and when it was controlled for by retrospective self-reports. RESULTS: Rates of contamination ranged from 62% to 67%. Without controlling for contamination, causal effect size estimates for internalizing behaviors were not statistically significant. Causal effects only became statistically significant after controlling contamination identified from either prospective or retrospective reports and effect sizes increased by between 17% and 54%. Controlling contamination had a smaller impact on effect size increases for externalizing behaviors but did produce a statistically significant overall effect, relative to the model ignoring contamination, when prospective methods were used. CONCLUSIONS: The presence of contamination in a nonmaltreated comparison group can underestimate the magnitude and statistical significance of causal effect size estimates, especially when investigating internalizing behavior problems. Addressing contamination can facilitate the replication of results across studies.

Cross-tissue comparison of telomere length and quality metrics of DNA among individuals aged 8 to 70 years.

Telomere length (TL) is an important biomarker of cellular aging, yet its links with health outcomes may be complicated by use of different tissues. We evaluated within- and between-individual variability in TL and quality metrics of DNA across five tissues using a cross-sectional dataset ranging from 8 to 70 years (N = 197). DNA was extracted from all tissue cells using the Gentra Puregene DNA Extraction Kit. Absolute TL (aTL) in kilobase pairs was measured in buccal epithelial cells, saliva, dried blood spots (DBS), buffy coat, and peripheral blood mononuclear cells (PBMCs) using qPCR. aTL significantly shortened with age for all tissues except saliva and buffy coat, although buffy coat was available for a restricted age range (8 to 15 years). aTL did not significantly differ across blood-based tissues (DBS, buffy coat, PBMC), which had significantly longer aTL than buccal cells and saliva. Additionally, aTL was significantly correlated for the majority of tissue pairs, with partial Spearman's correlations controlling for age and sex ranging from ⍴ = 0.18 to 0.51. We also measured quality metrics of DNA including integrity, purity, and quantity of extracted DNA from all tissues and explored whether controlling for DNA metrics improved predictions of aTL. We found significant tissue variation: DNA from blood-based tissues had high DNA integrity, more acceptable A260/280 and A260/230 values, and greater extracted DNA concentrations compared to buccal cells and saliva. Longer aTL was associated with lower DNA integrity, higher extracted DNA concentrations, and higher A260/230, particularly for saliva. Model comparisons suggested that incorporation of quality DNA metrics improves models of TL, although relevant metrics vary by tissue. These findings highlight the merits of using blood-based tissues and suggest that incorporation of quality DNA metrics as control variables in population-based studies can improve TL predictions, especially for more variable tissues like buccal and saliva.

Contamination in Observational Research on Child Maltreatment: A Conceptual and Empirical Review With Implications for Future Research.

Contamination is a methodological phenomenon occurring in child maltreatment research when individuals in an established comparison condition have, in reality, been exposed to maltreatment during childhood. The current paper: (1) provides a conceptual and methodological introduction to contamination in child maltreatment research, (2) reviews the empirical literature demonstrating that the presence of contamination biases causal estimates in both prospective and retrospective cohort studies of child maltreatment effects, (3) outlines a dual measurement strategy for how child maltreatment researchers can address contamination, and (4) describes modern statistical methods for generating causal estimates in child maltreatment research after contamination is controlled. Our goal is to introduce the issue of contamination to researchers examining the effects of child maltreatment in an effort to improve the precision and replication of causal estimates that ultimately inform scientific and clinical decision-making as well as public policy.

Epigenetic age acceleration as a biomarker for impaired cognitive abilities in adulthood following early life adversity and psychiatric disorders.

Background: Early life adversity and psychiatric disorders are associated with earlier declines in neurocognitive abilities during adulthood. These declines may be preceded by changes in biological aging, specifically epigenetic age acceleration, providing an opportunity to uncover genome-wide biomarkers that identify individuals most likely to benefit from early screening and prevention. Methods: Five unique epigenetic age acceleration clocks derived from peripheral blood were examined in relation to latent variables of general and speeded cognitive abilities across two independent cohorts: 1) the Female Growth and Development Study (FGDS; n = 86), a 30-year prospective cohort study of substantiated child sexual abuse and non-abused controls, and 2) the Biological Classification of Mental Disorders study (BeCOME; n = 313), an adult community cohort established based on psychiatric disorders. Results: A faster pace of biological aging (DunedinPoAm) was associated with lower general cognitive abilities in both cohorts and slower speeded abilities in the BeCOME cohort. Acceleration in the Horvath clock was significantly associated with slower speeded abilities in the BeCOME cohort but not the FGDS. Acceleration in the Hannum clock and the GrimAge clock were not significantly associated with either cognitive ability. Accelerated PhenoAge was associated with slower speeded abilities in the FGDS but not the BeCOME cohort. Conclusions: The present results suggest that epigenetic age acceleration has the potential to serve as a biomarker for neurocognitive decline in adults with a history of early life adversity or psychiatric disorders. Estimates of epigenetic aging may identify adults at risk of cognitive decline that could benefit from early neurocognitive screening.

The association of epigenetic age acceleration and depressive and anxiety symptom severity among children recently exposed to substantiated maltreatment.

Child maltreatment is a major risk factor for both depressive and anxiety disorders. However, many children exposed to maltreatment never meet diagnostic threshold for either disorder while experiencing only transitory symptoms post-exposure. Recent research suggests DNA methylation adds predictive value in explaining variation in the onset and course of multiple psychiatric disorders following exposure to child maltreatment. Epigenetic age acceleration (EAA), the biological aging of cells not attributable to chronological aging, is a stress-sensitive biomarker capturing genome-wide variation in DNA methylation with the potential to identify children who have been maltreated at greatest risk for depressive and anxiety disorders. The current study examined two EAA clocks appropriate for the pediatric population, the Horvath and Pediatric Buccal Epigenetic (PedBE) clocks, and their associations with depressive and anxiety symptom severity following child maltreatment. Children (N = 71) 8-15 years of age, all of whom were exposed to substantiated child maltreatment in the 12 months prior to study entry, were enrolled. Risk modeling adjusting for several confounders revealed that EAA estimated via the Horvath clock was significantly associated with more severe depressive and anxiety symptoms. The PedBE clock was not associated with either depressive or anxiety symptom severity. Sensitivity analyses demonstrated that EAA via the Horvath clock robustly predicted depressive and anxiety symptom severity across multiple modeling scenarios. Our findings advance existing research suggesting EAA, as estimated with the Horvath clock, may be a promising biomarker for identifying children at greatest risk for more severe depressive and anxiety symptoms following maltreatment.

Investigating the effects of maltreatment and acute stress on the concordance of blood and DNA methylation methods of estimating immune cell proportions.

BACKGROUND: Immune cell proportions can be used to detect pathophysiological states and are also critical covariates in genomic analyses. The complete blood count (CBC) is the most common method of immune cell proportion estimation, but immune cell proportions can also be estimated using whole-genome DNA methylation (DNAm). Although the concordance of CBC and DNAm estimations has been validated in various adult and clinical populations, less is known about the concordance of existing estimators among stress-exposed individuals. As early life adversity and acute psychosocial stress have both been associated with unique DNAm alterations, the concordance of CBC and DNAm immune cell proportion needs to be validated in various states of stress. RESULTS: We report the correlation and concordance between CBC and DNAm estimates of immune cell proportions using the Illumina EPIC DNAm array within two unique studies: Study 1, a high-risk pediatric cohort of children oversampled for exposure to maltreatment (N = 365, age 8 to 14 years), and Study 2, a sample of young adults who have participated in an acute laboratory stressor with four pre- and post-stress measurements (N = 28, number of observations = 100). Comparing CBC and DNAm proportions across both studies, estimates of neutrophils (r = 0.948, p < 0.001), lymphocytes (r = 0.916, p < 0.001), and eosinophils (r = 0.933, p < 0.001) were highly correlated, while monocyte estimates were moderately correlated (r = 0.766, p < 0.001) and basophil estimates were weakly correlated (r = 0.189, p < 0.001). In Study 1, we observed significant deviations in raw values between the two approaches for some immune cell subtypes; however, the observed differences were not significantly predicted by exposure to child maltreatment. In Study 2, while significant changes in immune cell proportions were observed in response to acute psychosocial stress for both CBC and DNAm estimates, the observed changes were similar for both approaches. CONCLUSIONS: Although significant differences in immune cell proportion estimates between CBC and DNAm exist, as well as stress-induced changes in immune cell proportions, neither child maltreatment nor acute psychosocial stress alters the concordance of CBC and DNAm estimation methods. These results suggest that the agreement between CBC and DNAm estimators of immune cell proportions is robust to exposure to child maltreatment and acute psychosocial stress.

Childhood maltreatment and DNA methylation: A systematic review.

Child maltreatment (CM) encompasses sexual abuse, physical abuse, emotional abuse, neglect, and exposure to domestic and family violence. Epigenetic research investigating CM has focused on differential DNA methylation (DNAm) in genes associated with the stress response, but there has been limited evaluation of the specific effects of subtypes of CM. This systematic review of literature investigating DNAm associated with CM in non-clinical populations aimed to summarise the approaches currently used in research, how the type of maltreatment and age of exposure were encoded via methylation, and which genes have consistently been associated with CM. A total of fifty-four papers were eligible for review, including forty-one candidate gene studies, eight epigenome-wide association studies, and five studies with a mixed design. The ways in which the various forms of CM were conceptualised and measured varied between papers. Future studies would benefit from assessments that employ conceptually robust definitions of CM, and that capture important contextual information such as age of exposure and subtype of CM.

Child maltreatment, parent-child relationship quality, and parental monitoring in relation to adolescent behavior problems: Disaggregating between and within person effects.

BACKGROUND: Parent-child relationship quality (PCRQ) and parental monitoring (PM) are associated with adolescent behavior problems following child maltreatment (CM). Whether these associations are best characterized as between (trait) or within-person (state) differences is unknown. OBJECTIVE: Disaggregate between and within-person effects for PCRQ and PM on adolescent behavior problems and test whether these effects vary as a function of prior CM. PARTICIPANTS AND SETTING: Participants (n = 941) are from the Longitudinal Studies on Child Abuse and Neglect (LONGSCAN). METHODS: Multi-level modeling was employed using PCRQ, PM, and adolescent behaviors assessed at ages 12, 14, and 16 and confirmed CM prior to age 12. RESULTS: At the between-person level, adolescents with higher average levels of PCRQ and PM had significantly lower initial levels of externalizing (b = -9.47 and -5.54, respectively, p's < 0.05; possible range 0-66) and internalizing behaviors (b = -4.45 and -6.41, respectively, p's < 0.001; possible range 0-62). At the within-person level, greater declines in externalizing and internalizing behaviors were found when individuals reported higher-than-usual levels of PCRQ (b = -4.99 and -2.59, respectively, for externalizing and internalizing, p's < 0.001) and PM (b = -3.58 and -1.69, respectively, for externalizing and internalizing, p's < 0.001). There was an interaction between PM and CM on internalizing behaviors over time (b = -1.15, p = 0.026). CONCLUSIONS: There are between and within-person effects of PCRQ and PM on adolescent behavior problems. Adolescents with CM histories and low levels of PM may be at risk for sustained internalizing behaviors.

The Flexible Regulation of Emotional Expression Scale for Youth (FREE-Y): Adaptation and Validation Across a Varied Sample of Children and Adolescents.

Flexible self-regulation has been shown to be an adaptive ability. This study adapted and validated the adult Flexible Regulation of Emotional Expression (FREE) Scale for use with youth (FREE-Y) in community and maltreatment samples. The FREE-Y measures the ability to flexibly enhance and suppress emotion expression across an array of hypothetical social scenarios. Participants (N = 654, 8-19 years) were included from three studies. Confirmatory factor analysis (CFA) confirmed a theoretically appropriate higher order factor structure. Using multiple-group CFAs, measurement invariance was achieved across maltreatment status, age, and gender. Reliabilities were adequate and construct validity was demonstrated through associations with measures of emotion regulation, psychopathology, IQ, and executive functioning. Group comparisons indicated lower Suppression and Flexibility scores for maltreated versus comparison participants. Findings suggest that the FREE-Y is a valid measure of expressive regulation ability in youth that can be applied across a range of populations.

Receptive Language Abilities for Females Exposed to Early Life Adversity: Modification by Epigenetic Age Acceleration at Midlife in a 30-Year Prospective Cohort Study.

OBJECTIVES: Deviations from normative trajectories of receptive language abilities following early life adversity (ELA) may indicate an elevated risk for advanced cognitive aging and related morbidities. Accelerated epigenetic aging at midlife may further identify those at greatest risk for advanced cognitive aging following ELA. We examined whether accelerations in epigenetic aging at midlife can identify those individuals who demonstrated the greatest change in receptive language abilities following ELA. METHODS: Data were drawn from the Female Growth and Development Study (n = 86), a 30-year prospective cohort study of females exposed to substantiated child sexual abuse (CSA), a severe ELA, and a non-CSA comparison condition. The Peabody Picture Vocabulary Test-Revised (PPVT-R) measured receptive language abilities on 6 occasions from childhood to mid-life. Interindividual differences in PPVT-R trajectories were examined in relation to CSA exposure and across 5 independent measures of epigenetic age acceleration derived from first (Horvath DNAmAge, Hannum DNAmAge) and second (GrimAge, PhenoAge, Dunedin Pace of Aging) generation epigenetic clocks. RESULTS: Quadratic growth models revealed that PPVT-R scores were significantly lower at age 25 for females exposed to CSA. Specifically, CSA exposed females had lower intercepts when GrimAge was accelerated and a smaller quadratic trend when PhenoAge was accelerated. DISCUSSION: ELA is associated with significant differences in development of receptive language abilities with the most pronounced differences observed for females with accelerated epigenetic ages at mid-life. These findings suggest that epigenetic age acceleration could serve as an indicator of differences in cognitive aging and portend to later adulthood cognitive functioning.

Respiratory Sinus Arrhythmia Change during Trauma-Focused Cognitive-Behavioral Therapy: Results from a Randomized Controlled Feasibility Trial.

Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is a well-established treatment for pediatric posttraumatic stress disorder (PTSD). Animal-assisted therapy (AAT) has been proposed as an adjunct to TF-CBT that may improve treatment effects through enhanced targeting of affect regulation, as indexed by specific changes in the respiratory sinus arrhythmia (RSA). The current study reports results from a randomized controlled feasibility trial (N = 33; Mage = 11.79 [SD = 3.08]; 64% White; 67% female) that measured RSA during Sessions 1, 4, 8, and 12 of a twelve-session TF-CBT protocol and tested whether: 1) TF-CBT + AAT achieved higher average RSA amplitudes relative to TF-CBT alone, and 2) RSA regulation, defined as less variability around person-specific RSA slopes during treatment, explained variation in post-treatment PTSD symptoms. Multilevel modeling failed to support an effect for TF-CBT + AAT on RSA amplitudes (δ001 = 0.08, p = 0.844). However, regardless of treatment condition, greater RSA withdrawal was observed within Sessions 4 (γ11 = -.01, p < .001) and 12 (γ13 = -.01, p = .015) relative to the Session 1 baseline. The average level of RSA amplitude in Session 8 was also significantly lower compared to Session 1 (γ02 = -0.70, p = .046). Intraindividual regression models demonstrated that greater RSA regulation predicted improved PTSD symptoms at post-treatment after adjusting for pre-treatment levels (b3 = 20.00, p = .012). These preliminary results offer support for future confirmatory trials testing whether affect regulation, as indexed by changes in RSA, is a mechanism of action for TF-CBT in the treatment of pediatric PTSD.

Obesity and accelerated epigenetic aging in a high-risk cohort of children.

New insights into mechanisms linking obesity to poor health outcomes suggest a role for cellular aging pathways, casting obesity as a disease of accelerated biological aging. Although obesity has been linked to accelerated epigenetic aging in middle-aged adults, the impact during childhood remains unclear. We tested the association between body mass index (BMI) and accelerated epigenetic aging in a cohort of high-risk children. Participants were children (N = 273, aged 8 to 14 years, 82% investigated for maltreatment) recruited to the Child Health Study, an ongoing prospective study of youth investigated for maltreatment and a comparison youth. BMI was measured as a continuous variable. Accelerated epigenetic aging of blood leukocytes was defined as the age-adjusted residuals of several established epigenetic aging clocks (Horvath, Hannum, GrimAge, PhenoAge) along with a newer algorithm, the DunedinPoAm, developed to quantify the pace-of-aging. Hypotheses were tested with generalized linear models. Higher age-and sex- adjusted z-scored BMI was significantly correlated with household income, blood cell counts, and three of the accelerated epigenetic aging measures: GrimAge (r = 0.31, P < .0001), PhenoAge (r = 0.24, P < .0001), and DunedinPoAm (r = 0.38, P < .0001). In fully adjusted models, GrimAge (ß = 0.07; P = .0009) and DunedinPoAm (ß = 0.0017; P < .0001) remained significantly associated with higher age- and sex-adjusted z-scored BMI. Maltreatment-status was not associated with accelerated epigenetic aging. In a high-risk cohort of children, higher BMI predicted epigenetic aging as assessed by two epigenetic aging clocks. These results suggest the association between obesity and accelerated epigenetic aging begins in early life, with implications for future morbidity and mortality risk.

Comparing qPCR and DNA methylation-based measurements of telomere length in a high-risk pediatric cohort.

Various approaches exist to assess population differences in biological aging. Telomere length (TL) is one such measure, and is associated with disease, disability and early mortality. Yet, issues surrounding precision and reproducibility are a concern for TL measurement. An alternative method to estimate TL using DNA methylation (DNAmTL) was recently developed. Although DNAmTL has been characterized in adult and elderly cohorts, its utility in pediatric populations remains unknown. We examined the comparability of leukocyte TL measurements generated using qPCR (absolute TL; aTL) to those estimated using DNAmTL in a high-risk pediatric cohort (N = 269; age: 8-13 years, 83% investigated for maltreatment). aTL and DNAmTL measurements were correlated with one another (r = 0.20, p = 0.001), but exhibited poor measurement agreement and were significantly different in paired-sample t-tests (Cohen's d = 0.77, p < 0.001). Shorter DNAmTL was associated with older age (r = -0.25, p < 0.001), male sex (ß = -0.27, p = 0.029), and White race (ß = -0.74, p = 0.008). By contrast, aTL was less strongly associated with age (r = -0.13, p = 0.040), was longer in males (ß = 0.31, p = 0.012), and was not associated with race (p = 0.820). These findings highlight strengths and limitations of high-throughput measures of TL; although DNAmTL replicated hypothesized associations, aTL measurements were positively skewed and did not replicate associations with external validity measures. These results also extend previous research in adults and suggest that DNAmTL is a sensitive TL measure for use in pediatric populations.

Integrating Animal-Assisted Therapy Into TF-CBT for Abused Youth With PTSD: A Randomized Controlled Feasibility Trial.

This clinical trial examined animal-assisted therapy (AAT) as an adjunct to Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) for abused youth with posttraumatic stress disorder (PTSD). Youth between the ages of 6 and 17 (M = 11.79, SD = 3.08) were randomized to receive standard TF-CBT or TF-CBT with adjunctive AAT (TF-CBT+AAT) employing retired service dogs. Feasibility metrics evaluating the addition of AAT were collected in addition to common clinical outcomes evaluated in TF-CBT trials. The inclusion of AAT increased the number of potential participants who declined participation and there were no noted benefits for treatment retention or satisfaction with services. Analyses showed that the inclusion of AAT did not enhance improvement of PTSD symptom severity (ß = .90, t = .94, p = .351) or a number of other outcomes. On the contrary, there were indications from analyses and clinician feedback that AAT may have attenuated improvement in many cases. This study identified a number of important feasibility considerations in the design of studies testing AAT. However, the results examining clinical outcomes suggest that the inclusion of AAT with TF-CBT in the treatment of maltreated youth with PTSD is not warranted at this time.

Controlling contamination in child maltreatment research: Impact on effect size estimates for child behavior problems measured throughout childhood and adolescence.

Contamination, when members of a comparison or control condition are exposed to the event or intervention under scientific investigation, is a methodological phenomenon that downwardly biases the magnitude of effect size estimates. This study tested a novel approach for controlling contamination in observational child maltreatment research. Data from The Longitudinal Studies of Child Abuse and Neglect (LONGSCAN; N = 1354) were obtained to estimate the risk of confirmed child maltreatment on trajectories of internalizing and externalizing behaviors before and after controlling contamination. Baseline models, where contamination was uncontrolled, demonstrated a risk for greater internalizing (b = .29, p < .001, d = .40) and externalizing (b = .14, p = .040, d = .19) behavior trajectories. Final models, where contamination was controlled by separating the comparison condition into subgroups that did or did not self-report maltreatment, also demonstrated risks for greater internalizing (b = .37, p < .001, d = .51) and externalizing (b = .22, p = .028, d = .29) behavior trajectories. However, effect size estimates in final models were 27.5%-52.6% larger compared to baseline models. Controlling contamination in child maltreatment research can strengthen effect size estimates for child behavior problems, aiding future child maltreatment research design and analysis.

Epigenetic Age Acceleration and Risk for Posttraumatic Stress Disorder following Exposure to Substantiated Child Maltreatment.

OBJECTIVE: Child maltreatment is among the strongest predictors of posttraumatic stress disorder (PTSD). However, less than 40% of children who have been maltreated are ever diagnosed with PTSD, suggesting that exposure to child maltreatment alone is insufficient to explain this risk. This study examined whether epigenetic age acceleration, a stress-sensitive biomarker derived from DNA methylation, explains variation in PTSD diagnostic status subsequent to child maltreatment. METHOD: Children and adolescents (N = 70; 65.7% female), 8-15 years of age (M = 12.00, SD = 2.37) and exposed to substantiated child maltreatment within the 12 months prior to study entry, were enrolled. Participants provided epithelial cheek cells via buccal swab for genotyping and quantification of epigenetic age acceleration within a case-control design. PTSD diagnostic status was determined using the Child PTSD Symptoms Scale according to the DSM-IV-TR algorithm. RESULTS: Epigenetic age acceleration predicted current PTSD status, revealing an effect size magnitude in the moderate range, OR = 2.35, 95% CI: 1.22- 4.51, after adjusting for sample demographics, polygenic risk for PTSD, and lifetime exposure to other childhood adversities. Supplemental analyses demonstrated that epigenetic age acceleration was related to a greater severity of PTSD arousal symptoms (r =.29, p =.015). There were no differential effects for child maltreatment subtype on epigenetic age acceleration or PTSD status. CONCLUSIONS: The biological embedding of child maltreatment may explain variation in PTSD diagnostic status and serve as a novel approach for informing selective prevention or precision-based therapeutics for those at risk for PTSD.

Child Maltreatment and Substance Use in Emerging Adulthood: Internalizing and Externalizing Behaviors at the Transition to Adolescence as Indirect Pathways.

One well-established outcome of child maltreatment is an increased likelihood of substance use in emerging adulthood. However, research identifying the indirect pathways that explain this relation is lacking, thereby limiting substance use prevention efforts for the child maltreatment population. The present study helped address this gap by accessing data from The Longitudinal Studies on Child Abuse and Neglect (LONGSCAN; n = 1,136), a prospective cohort study of child maltreatment from birth through age eighteen. Internalizing and externalizing problems at age twelve were examined as indirect effects of the relation between child maltreatment prior to age four and substance use at age eighteen. A multiple mediator model tested the total and specific indirect effects of internalizing and externalizing concerns while controlling for demographic risk factors. Results demonstrated that the total indirect effect for internalizing and externalizing behaviors was statistically significant, Standardized Point Estimate = 0.01, 95% CI: 0.00-0.02. Examination of the specific indirect effects revealed that only externalizing behaviors constituted an indirect pathway, Standardized Point Estimate = 0.01, 95% CI: 0.00-0.03. These results suggest that externalizing behaviors at the transition to adolescence are important intervention targets for reducing the risk for substance use in emerging adulthood in the child maltreatment population.