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The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.

Objectives: The current study aimed to examine: (1.1) causal beliefs about adolescent depression in a sample of adolescents with a clinical depression and their mothers and fathers; (1.2) within‐family overlap of causal beliefs; (2.1) mothers' and fathers' reflected causal beliefs about their child's perspective; (2.2) the accuracy of mothers' and fathers' reflected causal beliefs as related to their child's causal beliefs. Design: Qualitative study using a within‐family approach. Methods: Adolescents with a current clinical depression (MDD/dysthymia; N = 34) and their parents (N = 34 mothers, N = 26 fathers) were independently interviewed about their causal beliefs about the adolescents' depression. Parents were additionally interviewed about their perception of their child's causal beliefs (i.e., reflected causal beliefs). Results: The causal beliefs most frequently mentioned by adolescents, mothers and fathers are: characteristics of the child, social factors, school and various stressful experiences. Parent–child overlap was relatively low, specifically for the themes of bewilderment, cumulative effect and stressful life events, whereas overlap was relatively high for themes of social factors, school and stressful experiences outside of the family. Parents were relatively accurate in their reflected causal beliefs, but tended to underestimate their child's insights into possible causes of their depression. Accuracy of parents' reflected causal beliefs was particularly low for the theme cumulative effect and high for social factors. Conclusions: The various causal beliefs of adolescents and their parents could be used in therapeutic setting. Future research could examine whether (guided) conversations may promote alignment within families and treatment efficacy. [ABSTRACT FROM AUTHOR]

The early caregiving environment can have lasting effects on child mental health. Animal models suggest that glucocorticoid receptor gene (NR3C1) DNA methylation plays a mediating role in linking more responsive caregiving to improved behavioral outcomes by its impact on the stress regulatory system. In this longitudinal study, we examined whether children's NR3C1 methylation levels mediate an effect of maternal sensitivity in infancy on levels of child internalizing and externalizing behavior in a community sample. Maternal sensitivity of 145 mothers was rated at infant age 5 weeks, 12 months, and 30 months by observing mother–infant interactions. Buccal DNA methylation was assessed in the same children at age 6 years and maternal-reported internalizing and externalizing behavior was assessed at age 6 and 10 years. Higher sensitivity at age 5 weeks significantly predicted lower DNA methylation levels at two NR3C1 CpG loci, although methylation levels at these loci did not mediate an effect of maternal sensitivity on levels of child internalizing and externalizing behavior. Overall, the study provides evidence that maternal sensitivity in early infancy is associated with DNA methylation levels at loci involved in stress regulation, but the significance of this finding for child mental health remains unclear. [ABSTRACT FROM AUTHOR]

Background: Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied. Methods: Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views. Results: In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more. Conclusions: Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views. [ABSTRACT FROM AUTHOR]

Introduction: This randomized controlled trial examined the effectiveness of physical activity added to an intensive trauma-focused treatment (TFT) for post-traumatic stress disorder (PTSD) in comparison to adding non-physical control activities. Methods: A total of 119 patients with PTSD were randomly assigned to a physical activity condition (PA; n = 59) or a non-physical activity control condition (nPA; n = 60). The 8-day intensive TFT programme consisted of daily prolonged exposure, EMDR therapy, and psychoeducation, which was complemented with physical activities versus controlled mixtures of guided (creative) tasks. As a primary outcome, the change in clinician and self-reported PTSD symptoms from pre-to post-treatment and at 6 months follow-up were measured. Results: Intent-to-treat linear mixed-effects models showed no significant differences between the PA and nPA conditions on change in PTSD severity. Clinician and self-reported PTSD symptoms significantly decreased for both conditions, with large effect sizes (e.g., CAPS-5 dpre-post = 2.28). At post-treatment, 80.0% in the PA, and 82.7% in the nPA condition no longer met the diagnostic criteria for PTSD. Regarding the loss of Complex PTSD diagnoses this was 92.5% and 95.0%, respectively. Conclusion: Either with additional physical or non-physical activities, intensive TFT is very effective for the treatment of (Complex) PTSD, as reflected by large effect sizes and loss of diagnostic status in both groups. [ABSTRACT FROM AUTHOR]

Parent-child agreement on child maltreatment was examined in a multigenerational study. Questionnaires on perpetrated and experienced child maltreatment were completed by 138 parent-child pairs. Multi-level analyses were conducted to explore whether parents and children agreed about levels of parent-to-child maltreatment (convergence), and to examine whether parents and children reported equal levels of child maltreatment (absolute differences). Direct and moderating effects of age and gender were examined as potential factors explaining differences between parent and child report. The associations between parent- and child-reported maltreatment were significant for all subtypes, but the strength of the associations was low to moderate. Moreover, children reported more parent-to-child neglect than parents did. Older participants reported more experienced maltreatment than younger participants, without evidence for differences in actual exposure. These findings support the value of multi-informant assessment of child maltreatment to improve accuracy, but also reveal the divergent perspectives of parents and children on child maltreatment., Author(s): Laura H.C.G. Compier-de Block [sup.1] , Lenneke R.A. Alink [sup.1] [sup.2] , Mariëlle Linting [sup.1] , Lisa J.M. van den Berg [sup.3] , Bernet M. Elzinga [sup.3] , Alexandra [...]

One of the proposed mechanisms linking childhood stressor exposure to negative mental and physical health outcomes in later life is cellular aging. In this prospective, longitudinal, and pre‐registered study, we examined the association between a cumulative pattern of childhood risk exposure from age 6 to age 10 (i.e., poor maternal mental health, parental relationship problems, family/friend death, bullying victimization, poor quality friendships) and change in two biomarkers of cellular aging (i.e., telomere length, epigenetic age) from age 6 to age 10 in a Dutch low‐risk community sample (n = 193). We further examined the moderating effect of cortisol reactivity at age 6. Ordinary Least Squares regression analyses revealed no significant main effects of childhood risk exposure on change in cellular aging, nor a moderation effect of child cortisol reactivity. Secondary findings showed a positive correlation between telomere length and cortisol reactivity at age 6, warranting further investigation. More research in similar communities is needed before drawing strong conclusions based on the null results. Previous research in high‐adversity risk samples suggests an association between childhood stressor exposure and accelerated cellular aging. Our null‐findings from a longitudinal community sample indicate that such link between childhood stressor exposure and accelerated cellular aging might not be present in low‐adversity risk samples. Furthermore, our study uncovers an association between telomere length and cortisol reactivity and supports the notions of a lack of association between different biomarkers of cellular aging and a period of telomere length stability in childhood. [ABSTRACT FROM AUTHOR]

The eye region is thought to play an important role in the ability to accurately infer others' feelings, or empathic accuracy (EA), which is an important skill for social interaction. However, most past studies used static pictures, including only visual information, and knowledge about the contribution of the eye region to EA when visual information is presented together with verbal content is lacking. We therefore examined whether eye gazing contributes to EA during videos of emotional autobiographical stories including both visual and verbal content. One hundred seven perceivers watched videos of targets talking about positive and negative life events and continuously rated the targets' feelings during the videos. Simultaneously, perceivers' eyes were tracked. After each video, perceivers reported on their feelings and the extent to which they empathized with and took the perspective of the targets. In contrast to studies using static pictures, we found that gazing to the eyes of targets during the videos did not significantly contribute to EA. At the same time, results on the association between the amount of gaze towards the eye region of targets and perceivers' state and trait empathy ratings suggest that eye gazing might signal empathy and social engagement to others. [ABSTRACT FROM AUTHOR]

Over the past three decades, functional magnetic resonance imaging (fMRI) has become crucial to study how cognitive processes are implemented in the human brain. However, the question of whether participants recruited into fMRI studies differ from participants recruited into other study contexts has received little to no attention. This is particularly pertinent when effects fail to generalize across study contexts: for example, a behavioural effect discovered in a non-imaging context not replicating in a neuroimaging environment. Here, we tested the hypothesis, motivated by preliminary findings (N  = 272), that fMRI participants differ from behaviour-only participants on one fundamental individual difference variable: trait anxiety. Analysing trait anxiety scores and possible confounding variables from healthy volunteers across multiple institutions (N  = 3317), we found robust support for lower trait anxiety in fMRI study participants, consistent with a sampling or self-selection bias. The bias was larger in studies that relied on phone screening (compared with full in-person psychiatric screening), recruited at least partly from convenience samples (compared with community samples), and in pharmacology studies. Our findings highlight the need for surveying trait anxiety at recruitment and for appropriate screening procedures or sampling strategies to mitigate this bias. [ABSTRACT FROM AUTHOR]

Social feedback, such as praise or critique, profoundly impacts our mood and social interactions. It is unknown, however, how parents experience praise and critique about their child and whether their mood and neural responses to such 'vicarious' social feedback are modulated by parents' perceptions of their child. Parents (n  = 60) received positive, intermediate and negative feedback words (i.e. personality characteristics) about their adolescent child during a magnetic resonance imaging scan. After each word, parents indicated their mood. After positive feedback their mood improved and activity in ventromedial prefrontal cortex and posterior cingulate cortex/precuneus increased. Negative feedback worsened parents' mood, especially when perceived as inapplicable to their child, and increased activity in anterior cingulate cortex, anterior insula, dorsomedial prefrontal cortex and precuneus. Parents who generally viewed their child more positively showed amplified mood responses to both positive and negative feedback and increased activity in dorsal striatum, inferior frontal gyrus and insula in response to negative feedback. These findings suggest that vicarious feedback has similar effects and engages similar brain regions as observed during feedback about the self and illustrates this is dependent on parents' beliefs of their child's qualities and flaws. Potential implications for parent–child dynamics and children's own self-views are discussed. [ABSTRACT FROM AUTHOR]

Maternal antenatal depression strongly influences child mental health but with considerable inter-individual variation that is, in part, linked to genotype. The challenge is to effectively capture the genotypic influence. We outline a novel approach to describe genomic susceptibility to maternal antenatal depression focusing on child emotional/behavioral difficulties. Two cohorts provided measures of maternal depression, child genetic variation, and child mental health symptoms. We constructed a conventional polygenic risk score (PRS) for attention-deficit/hyperactivity disorder (ADHD) (PRSADHD) that significantly moderated the association between maternal antenatal depression and internalizing problems at 60 months (p = 2.94 × 10−4, R2 =.18). We then constructed an interaction PRS (xPRS) based on a subset of those single nucleotide polymorphisms from the PRSADHD that most accounted for the moderation of the association between maternal antenatal depression and child outcome. The interaction between maternal antenatal depression and this xPRS accounted for a larger proportion of the variance in child emotional/behavioral problems than models based on any PRSADHD (p = 5.50 × 10−9, R2 =.27), with similar findings in the replication cohort. The xPRS was significantly enriched for genes involved in neuronal development and synaptic function. Our study illustrates a novel approach to the study of genotypic moderation on the impact of maternal antenatal depression on child mental health and highlights the utility of the xPRS approach. These findings advance our understanding of individual differences in the developmental origins of mental health. [ABSTRACT FROM AUTHOR]

Child-driven genetic factors can contribute to negative parenting and may increase the risk of being maltreated. Experiencing childhood maltreatment may be partly heritable, but results of twin studies are mixed. In the current study, we used a cross-sectional extended family design to estimate genetic and environmental effects on experiencing child maltreatment. The sample consisted of 395 individuals (225 women; M age = 38.85 years, rangeage = 7–88 years) from 63 families with two or three participating generations. Participants were oversampled for experienced maltreatment. Self-reported experienced child maltreatment was measured using a questionnaire assessing physical and emotional abuse, and physical and emotional neglect. All maltreatment phenotypes were partly heritable with percentages for h 2 ranging from 30% (SE = 13%) for neglect to 62% (SE = 19%) for severe physical abuse. Common environmental effects (c 2) explained a statistically significant proportion of variance for all phenotypes except for the experience of severe physical abuse (c 2 = 9%, SE = 13%, p =.26). The genetic correlation between abuse and neglect was ρg =.73 (p =.02). Common environmental variance increased as socioeconomic status (SES) decreased (p =.05), but additive genetic and unique environmental variances were constant across different levels of SES. [ABSTRACT FROM AUTHOR]

Background: Experiencing maltreatment during childhood exerts substantial stress on the child and increases the risk for overweight and obesity later in life. The current study tests whether hair cortisol—a measure of chronic stress—and its metabolite cortisone mediate the relation between abuse and neglect on the one hand, and body mass index (BMI) on the other. Method: The sample consisted of 249 participants aged 8 to 87 years (M = 36.13, SD = 19.33). We collected data on child abuse and neglect using questionnaires, measured cortisol and cortisone concentrations in hair, and BMI. In a structural model, the effects of abuse and neglect on hair cortisol, hair cortisone, and BMI were tested, as well as the covariance between hair cortisol and BMI, and hair cortisone and BMI. Results: Within the sample, 23% were overweight but not obese and 14% were obese. Higher levels of experienced abuse were related to higher cortisone concentrations in hair (β = 0.24, p <.001) and higher BMI (β = 0.17, p =.04). Neglect was not related to hair cortisol, hair cortisone, or BMI. Hair cortisol and cortisone did not mediate the association between maltreatment, and BMI. Sensitivity analyses demonstrate the same pattern of results in a subsample of adult participants currently not living with their parents. However, in younger participants who were still living with their parents, the associations between abuse and cortisone (β = 0.14, p =.35) and abuse and BMI (β = 0.02, p =.92) were no longer significant. Conclusion: These findings confirm that experiencing abuse is related to higher BMI but suggest that hair cortisol and cortisone are not the mechanism underlying the association between child maltreatment and BMI. This is the first study to show abuse may be associated to elevated concentrations of hair cortisone—evidence of long-term alterations in chronic stress levels. Future research may benefit from exploring the effects of maltreatment on weight gain in longitudinal designs, including measures of other potential mediators such as eating as a coping mechanism, and more direct indicators of metabolic health. [ABSTRACT FROM AUTHOR]

In the current study a three-generational design was used to investigate intergenerational transmission of child maltreatment (ITCM) using multiple sources of information on child maltreatment: mothers, fathers and children. A total of 395 individuals from 63 families reported on maltreatment. Principal Component Analysis (PCA) was used to combine data from mother, father and child about maltreatment that the child had experienced. This established components reflecting the convergent as well as the unique reports of father, mother and child on the occurrence of maltreatment. Next, we tested ITCM using the multi-informant approach and compared the results to those of two more common approaches: ITCM based on one reporter and ITCM based on different reporters from each generation. Results of our multi-informant approach showed that a component reflecting convergence between mother, father, and child reports explained most of the variance in experienced maltreatment. For abuse, intergenerational transmission was consistently found across approaches. In contrast, intergenerational transmission of neglect was only found using the perspective of a single reporter, indicating that transmission of neglect might be driven by reporter effects. In conclusion, the present results suggest that including multiple informants may be necessary to obtain more valid estimates of ITCM. [ABSTRACT FROM AUTHOR]

Although childhood maltreatment has been shown to compromise adaptive parental behavior, little is known what happens in terms of physiological regulation when parents with a history of childhood maltreatment interact with their offspring. Using a sample of 229 parents (131 women), the present study examined whether childhood maltreatment experiences are associated with parents' behavioral and autonomic responses while resolving conflict with their offspring. Self‐reported experienced child maltreatment was measured using a questionnaire assessing abuse and neglect. Parents (Mage = 52.7 years, rangeage = 26.6–88.4 years) and their offspring (Mage = 24.6 years, rangeage = 7.5–65.6 years) participated in a videotaped parent–offspring conflict interaction task. Parental warmth, negativity, and emotional support were coded. In addition, their pre‐ejection period and respiratory sinus arrhythmia were measured as indicators of underlying sympathetic and parasympathetic nervous system reactivity, respectively. Findings demonstrated that experiences of abuse and neglect were associated with behavioral and physiological responses in different ways. Separating these two types of maltreatment in research and in clinical practice might be important. [ABSTRACT FROM AUTHOR]

Mental illness is highly prevalent and runs in families. Mental disorders are considered to enhance the risk for the development of psychopathology in the offspring. This heightened risk is related to the separate and joint effects of inherited genetic vulnerabilities for psychopathology and environmental influences. The early years of life are suggested to be a key developmental phase in the intergenerational psychopathology transmission. Available evidence supports the idea that early exposure to parental psychopathology, during the pregnancy and first postpartum year, may be related to child psychological functioning beyond the postpartum period, up to adulthood years. This not only highlights the importance of intervening early to break the chain of intergenerational transmission of psychopathology but also raises the question of whether early interventions targeting parental mental disorders in this period may alleviate these prolonged adverse effects in the infant offspring. The current article focuses on the specific risk of psychopathology conveyed from mentally ill parents to the offspring during the pregnancy and first postpartum year. We first present a summary of the available evidence on the associations of parental perinatal mental illness with infant psychological outcomes at the behavioral, biological, and neurophysiological levels. Next, we address the effects of early interventions and discuss whether these may mitigate the early intergenerational transmission of risk for psychopathology. The summarized evidence supports the idea that psychopathology-related changes in parents' behavior and physiology in the perinatal period are related to behavioral, biological, and neurophysiological correlates of infant psychological functioning in this period. These alterations may constitute risk for later development of child and/or adult forms of psychopathology and thus for intergenerational transmission. Targeting psychopathology or mother-infant interactions in isolation in the postnatal period may not be sufficient to improve outcomes, whereas interventions targeting both maternal psychopathology and mother-infant interactions seem promising in alleviating the risk of early transmission. [ABSTRACT FROM AUTHOR]

Child maltreatment has been associated with various cumulative risk factors. However, little is known about the extent to which genetic and environmental factors contribute to individual differences between parents in perpetrating child maltreatment. To estimate the relative contribution of genetic and environmental factors to perpetrating maltreatment we used a parent-based extended family design. Child-reported perpetrated maltreatment was available for 556 parents (283 women) from 63 families. To explore reporter effects (i.e., child perspective on maltreatment), child reports were compared to multi-informant reports. Based on polygenic model analyses, most of the variance related to the perpetration of physical abuse and emotional neglect was explained by common environmental factors (physical abuse: c 2 = 59%, SE = 12%, p =.006; emotional neglect: c 2 = 47%, SE = 8%, p <.001) whereas genetic factors did not significantly contribute to the model. For perpetrated emotional abuse, in contrast, genetic factors did significantly contribute to perpetrated emotional abuse (h 2 = 33%, SE = 8%, p <.001), whereas common environment factors did not. Multi-informant reports led to similar estimates of genetic and common environmental effects on all measures except for emotional abuse, where a multi-informant approach yielded higher estimates of the common environmental effects. Overall, estimates of unique environment, including measurement error, were lower using multi-informant reports. In conclusion, our findings suggest that genetic pathways play a significant role in perpetrating emotional abuse, while physical abuse and emotional neglect are transmitted primarily through common environmental factors. These findings imply that interventions may need to target different mechanisms dependings on maltreatment type. [ABSTRACT FROM AUTHOR]

This study investigated associations of the Incredible Years (IY) parenting program with children's DNA methylation. Participants were 289 Dutch children aged 3–9 years (75% European ancestry, 48% female) with above‐average conduct problems. Saliva was collected 2.5 years after families were randomized to IY or care as usual (CAU). Using an intention‐to‐treat approach, confirmatory multiple‐regression analyses revealed no significant differences between the IY and CAU groups in children's methylation levels at the NR3C1 and FKBP5 genes. However, exploratory epigenome‐wide analyses revealed nine differentially methylated regions between groups, coinciding with SLAMF1, MITF, FAM200B, PSD3, SNX31, and CELSR1. The study provides preliminary evidence for associations of IY with children's salivary methylation levels and highlights the need for further research into biological outcomes of parenting programs. [ABSTRACT FROM AUTHOR]

Rejection by parents is an important aspect of child maltreatment. Altered neural responses to social rejection have been observed in maltreated individuals. The current study is the first to examine the impact of experienced and perpetrated abuse and neglect on neural responses to social exclusion by strangers versus family using a multigenerational family design, including 144 participants. The role of neural reactivity to social exclusion in the intergenerational transmission of maltreatment was also examined. Exclusion by strangers was especially associated with increased activation in the left insula, while exclusion by a family member was mainly associated with increased activation in the ACC. Neural reactivity to social exclusion by strangers in the insula, ACC and dmPFC, was associated with experienced maltreatment but not with perpetrated maltreatment. In abusive parents, altered neural reactivity during exclusion was found in other brain areas, indicating different neural correlates of experienced and perpetrated maltreatment. Hence, no mechanisms could be identified that are involved in the transmission of maltreatment. Hypersensitivity to social rejection by strangers in neglected individuals underscores the importance to distinguish between effects of abuse and neglect and suggests that the impact of experiencing rejection and maltreatment by your own parents extends beyond the family context. [ABSTRACT FROM AUTHOR]