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The five chapters and epilogue of this special issue present theoretical and empirical contributions on the relevance of attachment theory to cognitive development and education. A literature review is followed by explorations of attachment theory and emotions, cognitive development, literacy, and the communication effectiveness of the mother. (SLD)

Objective: During the Holocaust, extreme trauma was inflicted on children who experienced it. Two questions were central to the current investigation. First, do survivors of the Holocaust still show marks of their traumatic experiences, even after more than 50 years? Second, was the trauma passed on to the next generation? Method: Careful matching of Holocaust survivors and comparison subjects was employed to form a research study design with three generations, including 98 families with a grandmother, a mother, and an infant, who engaged in attachment--and trauma-related interviews, questionnaires, and observational procedures. Results: Holocaust survivors (now grandmothers) showed more signs of traumatic stress and more often lack of resolution of trauma than comparison subjects, but they were not impaired in general adaptation. Also, the traumatic effects did not appear to transmit across generations. Conclusions: Holocaust survivors may have been able to protect their daughters from their war experiences, although they themselves still suffer from the effects of the Holocaust.

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15–17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype–phenotype map than previously anticipated.

IMPORTANCE: Behavior problems are one of the most common mental health disorders in childhood and can undermine children’s health, education, and employment outcomes into adulthood. There are few effective interventions for early childhood. OBJECTIVE: To test the clinical effectiveness of a brief parenting intervention, the Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD), in reducing behavior problems in children aged 12 to 36 months. DESIGN, SETTING, AND PARTICIPANTS: The Healthy Start, Happy Start study was a 2-group, parallel-group, researcher-blind, multisite randomized clinical trial conducted via health visiting services in 6 National Health Service trusts in England. Baseline and 5-month follow-up data were collected between July 30, 2015, and April 27, 2018. Of 818 eligible families, 227 declined to participate, and 300 were randomized into the trial. Target participants were caregivers of children who scored in the top 20% for behavior problems on the Strengths and Difficulties Questionnaire. Participants were randomly allocated on a 1:1 basis to receive either VIPP-SD (n = 151) or usual care (n = 149), stratified by site and number of participating caregivers. Analysis was performed on an intention-to-treat basis. Statistical analysis was performed from September 5, 2019, to January 17, 2020. INTERVENTIONS: All families continued to access usual care. Families allocated to VIPP-SD were offered 6 home-based video-feedback sessions of 1 to 2 hours’ duration every 2 weeks. MAIN OUTCOMES AND MEASURES: The primary outcome was the score on an early childhood version of the Preschool Parental Account of Children’s Symptoms, a semistructured interview of behavior symptoms, at 5 months after randomization. Secondary outcomes included caregiver-reported behavior problems on the Child Behavior Checklist and the Strengths and Difficulties Questionnaire. RESULTS: Among 300 participating children (163 boys [54%]; mean [SD] age, 23.0 [6.7] months), primary outcome data were available for 140 of 151 VIPP-SD participants (93%) and 146 of 149 usual care participants (98%). There was a mean difference in the total Preschool Parental Account of Children’s Symptoms score of 2.03 (95% CI, 0.06-4.01; P = .04; Cohen d = 0.20 [95% CI, 0.01-0.40]) between trial groups, with fewer behavior problems in the VIPP-SD group, particularly conduct symptoms (mean difference, 1.61 [95% CI, 0.44-2.78]; P = .007; d = 0.30 [95% CI, 0.08-0.51]). Other child behavior outcomes showed similar evidence favoring VIPP-SD. No treatment or trial-related adverse events were reported. CONCLUSIONS AND RELEVANCE: This study found that VIPP-SD was effective in reducing symptoms of early behavior problems in young children when delivered in a routine health service context. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN58327365

Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene–environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene–environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health.

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N= 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r= 0.74, p= 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

ABSTRACTBullying among children is ubiquitous and associated with pervasive mental health problems. However, little is known about the biological pathways that change after exposure to bullying. Epigenome-wide changes in DNA methylation in peripheral blood were studied from pre- to post measurement of bullying exposure, in a longitudinal study of the population-based Generation R Study and Avon Longitudinal Study of Parents and Children (combined n = 1,352). Linear mixed-model results were meta-analysed to estimate how DNA methylation changed as a function of exposure to bullying. Sensitivity analyses including co-occurring child characteristics and risks were performed, as well as a Gene Ontology analysis. A candidate follow-up was employed for CpG (cytosine-phosphate-guanine) sites annotated to 5-HTTand NR3C1. One site, cg17312179, showed small changes in DNA methylation associated to bullying exposure (b = −2.67e-03, SE = 4.97e-04, p = 7.17e-08). This site is annotated to RAB14, an oncogene related to Golgi apparatus functioning, and its methylation levels decreased for exposed but increased for non-exposed. This result was consistent across sensitivity analyses. Enriched Gene Ontology pathways for differentially methylated sites included cardiac function and neurodevelopmental processes. Top CpG sites tended to have overall low levels of DNA methylation, decreasing in exposed, increasing in non-exposed individuals. There were no gene-wide corrected findings for 5-HTTand NR3C1. This is the first study to identify changes in DNA methylation associated with bullying exposure at the epigenome-wide significance level. Consistent with other population-based studies, we do not find evidence for strong associations between bullying exposure and DNA methylation.

Decisions regarding out-of-home placement of children are complicated and of high impact for children and parents. Previous studies show low agreement between professionals on these decisions, and research regarding the influence of characteristics of decision-makers on the content of the decisions taken remains inconclusive. This study explored the relation between general and psychological characteristics of 144 professionals (child welfare professionals, children’s court judges, and master students) using vignettes and questionnaires. Professionals’ mind-set regarding the ability of parents to achieve change (parent-specific mind-set) and their attitude toward the harmfulness of out-of-home placements were related to their decision-making. General decision-maker factors (the professional’s background and work experience), the mind-set toward the ability of people in general to change (dispositional mind-set), and professionals’ attitude toward the effectiveness of out-of-home placements were not related to their decisions. This field of practice needs to reflect on the role of implicit beliefs in making placement decisions about children.

•Adult attachment is transmitted to the next generation.•Sensitive parenting is an important link between parent attachment representation and child attachment behavior.•Sensitive parenting explains only part of the intergenerational transmission of attachment.•Parental mentalization cannot bridge the transmission gap.•Attachment-relevant parenting needs to be broadened to a multi-dimensional concept of parenting.

Fathers have an increasingly important role in the family and contribute through their sensitive responsiveness to positive child development. Research on parenting more often included fathers as caregivers in the past two decades. We present a neurobiological model of sensitive responsive parenting with a role for fathers' hormonal levels and neural connectivity and processing of infant signals. We tested this model in a research program (“Father Trials”) with correlational and randomized experimental studies, and we review the results of these studies. So far, interaction-focused behavioral interventions seem most promising in supporting fathers’ sensitive responsiveness, even though the mechanisms are still uncharted.

•Intervention efforts aimed at child problems prove only modestly effective due to heterogeneity in their efficacy.•Experimental-intervention research reveals that some children benefit more from intervention than others caused by their genetic make-up.•Children most negatively affected by adverse experiences also benefit the most from supportive ones.•More work is needed to illuminate underlying neurobiological mechanisms.

•Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) is reviewed.•VIPP-SD is based on attachment theory and social learning theory.•VIPP-SD aims at promoting sensitive parenting and firm limit setting in at risk families and in child care.•In a meta-analysis twelve randomized controlled trials on VIPP-SD are tested.•VIPP-SD significantly promotes sensitive caregiving and positive child outcomes.

•Protective parenting is an important but neglected part of parenting.•Infant attachment behavior and protective parenting are complementary phenotypes rooted in evolution, in non-human animals as well as in the human species.•Prenatal protective parenting is visible in intuitive pathogen avoidance during pregnancy.•Oxytocin stimulates protective parenting in mothers.•Protective parenting is a multidimensional construct to be studied from an interdisciplinary perspective.

Low or excessive sleep duration has been associated with multiple outcomes, but the biology behind these associations remains elusive. Specifically, genetic studies in children are scarce. In this study, we aimed to: (1) estimate the proportion of genetic variance of sleep duration in children attributed to common single nucleotide polymorphisms (SNPs), (2) identify novel SNPs associated with sleep duration in children, and (3) investigate the genetic overlap of sleep duration in children and related metabolic and psychiatric traits.

ABSTRACTPrenatal maternal stress exposure has been associated with neonatal differential DNA methylation. However, the available evidence in humans is largely based on candidate gene methylation studies, where only a few CpG sites were evaluated. The aim of this study was to examine the association between prenatal exposure to maternal stress and offspring genome-wide cord blood methylation using different methods. First, we conducted a meta-analysis and follow-up pathway analyses. Second, we used novel region discovery methods [i.e., differentially methylated regions (DMRs) analyses]. To this end, we used data from two independent population-based studies, the Generation R Study (n = 912) and the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 828), to (i) measure genome-wide DNA methylation in cord blood and (ii) extract a prenatal maternal stress composite. The meta-analysis (ntotal= 1,740) revealed no epigenome-wide (meta P<1.00e-07) associations of prenatal maternal stress exposure with neonatal differential DNA methylation. Follow-up analyses of the top hits derived from our epigenome-wide meta-analysis (meta P<1.00e-04) indicated an over-representation of the methyltransferase activity pathway. We identified no Bonferroni-corrected (P<1.00e-06) DMRs associated with prenatal maternal stress exposure. Combining data from two independent population-based samples in an epigenome-wide meta-analysis, the current study indicates that there are no large effects of prenatal maternal stress exposure on neonatal DNA methylation. Such replication efforts are essential in the search for robust associations, whether derived from candidate gene methylation or epigenome-wide studies.

In the present meta-analysis 627 Strange Situation Procedures (SSP; Ainsworth, Blehar, Waters, & Wall, 1978) from 17 Italian infant attachment studies and 2,258 Adult Attachment Interviews (AAI; Main, Kaplan, & Cassidy, 1985) from 50 Italian adult attachment studies were included. All studies were published between 1990 and 2009. Our aim was to test the universality hypothesis of attachment theory in this Italian database. Results indicated that the majority of nonclinical Italian infants were classified as securely attached (53%); similarly, the majority of nonclinical Italian adults were secure (60%). Although cross-cultural similarities provide evidence for the universality hypothesis of attachment theory, our meta-analysis revealed also interesting cultural specificities. First, nonclinical Italian infants’ distribution showed an overrepresentation of avoidant attachments compared to the normative distribution. Second, the underrepresentation of unresolved loss among Italian nonclinical adults was noteworthy.

Inconsistenties have been reported with regard to an association between val66met, a polymorphism on the BDNF gene, and hippocampal volume. We performed a systematic review and a meta‐analysis to determine the magnitude and direction of this putative association and estimated the potential influence of demographic, clinical, and methodological characteristics of studies. Tests of publication bias and time‐related trends were performed and statistical power of the included studies was calculated. The literature search for MRI studies on differences in total hippocampal volume as a function of BDNF val66met returned 25 records that fulfilled our criteria (total N = 3,620). Meta‐analysis showed that carriers of a met allele had lower hippocampal volumes relative to val/val homozygotes (d = 0.13, P= 0.02). Between‐study heterogeneity in effect size estimates was substantial (Q = 54.47, P< .001) and this could not be explained by demographic, clinical, and methodological differences across studies. Funnel plot inspection and trim‐and‐fill estimations suggested evidence for publication bias and effect sizes decreased substantially over the years (Pearson's r = −0.54, P< .01). All included studies were underpowered. This meta‐analysis shows that carriers of a met allele have lower total hippocampal volumes relative to val/val homozygotes. However, effect sizes converged closer to null with virtually each attempt at replication and were based on underpowered studies. Altogether, this may call into question whether the observed effect is a genuine biological effect of the met allele or whether it is subject to a winners curse, with large effect sizes found in a few early studies and increasingly smaller effect sizes in later studies. © 2012 Wiley Periodicals, Inc.

Parents' ability to appropriately respond to infant crying is essential for parental care and has been found to relate to parents' own childhood experiences. Additionally, childhood experiences can affect endocrine factors, which may subsequently affect behavior. In the current study, preregistered on https://osf.io/hwgtu, we examined in expectant and new fathers (N = 152) associations between experiences of maltreatment in their own childhood, hair cortisol and testosterone concentrations and their ability to modulate handgrip force when exposed to infant crying. Cortisol and testosterone were quantified from the 1 cm of hair most proximal to the scalp using Liquid chromatography-tandem mass spectrometry. Participants were asked to squeeze a handgrip dynamometer at full and half strength while listening to infant cries and control sounds. Results indicated that fathers who experienced more childhood maltreatment used more excessive handgrip force during infant cry sounds. Hair cortisol and testosterone were not related to either experienced childhood maltreatment or handgrip strength modulation. These findings confirm that fathers’ early experiences of maltreatment reduce their ability to modulate their behavioral responses during infant cries, but suggest that hair cortisol and testosterone concentrations do not identify the underlying mechanism of this association.

To investigate the effect of the mental representation of attachment on information processing, 28 anxiety disorder outpatients, as diagnosed by the Anxiety Disorders Interview Schedule—Revised, were administered the Adult Attachment Interview and the State–Trait Anxiety Inventory. They also completed an emotional Stroop task with subliminal and supraliminal exposure conditions, a free recall memory task, and a recognition test. All tasks contained threatening, neutral, and positively valenced stimuli. A nonclinical comparison group of 56 participants completed the same measures. Results on the Stroop task showed color-naming interference for threatening words in the supraliminal condition only. Nonclinical participants with insecure attachment representations showed a global response inhibition to the Stroop task. Clinical participants with secure attachment representations showed the largest Stroop interference of the threatening words compared to the other groups. Results on the free recall task showed superior recall of all types of stimuli by participants with secure attachment representations. In the outpatient group, participants with secure attachment representations showed superior recall of threatening words on the free recall task, compared to insecure participants. Results on the recognition task showed no differences between attachment groups. We conclude that secure attachment representations are characterized by open communication about and processing of threatening information, leading to less defensive exclusion of negative material during the attentional stage of information processing and to better recall of threatening information in a later stage. Attachment insecurity, but not the type of insecurity, seems a decisive factor in attention and memory processes.

Several attachment-based intervention studies have been performed, with varying success. An important question is whether short-term interventions can be successful in promoting parental sensitivity and security of infant-parent attachment as well as in changing parental representations of attachment. We investigated this issue in an exploratory way in a case study. A short-term home-based intervention with written material and video feedback, which was effective regarding parental sensitivity and infant security in a former study, was provided a parent who revealed an insecure attachment representation in the Adult Attachment Interview. The intervention sessions were expanded with discussions about past and present experiences of attachment. After four intervention sessions the mother's behavior towards her child was rated as more sensitive than before the intervention. Also, the infant-mother attachment, as observed in the Strange Situation, appeared to be more secure. Nevertheless, in a second Adult Attachment Interview administered after the intervention, the mother showed again an insecure representation of attachment. Possible implications of these results are discussed.

A study on attachment in indigenous Dutch families and in families who came to the Netherlands from Surinam-a former Dutch colony in South America is described. Sixty-five mothers and their infants participated, including 26 mothers who had immigrated from Surinam. Attachment behaviours and maternal responsiveness were recorded in the Strange Situation and in free play. The Infant Characteristics Questionnaire, and a questionnaire on child-rearing attitudes were completed. In the Surinam-Dutch group, maternal responsiveness was related to quality of attachment, although the Surinam-Dutch mothers scored significantly lower on the responsiveness scale than the Dutch mothers. The attachment classification distribution of the Surinam-Dutch dyads did not significantly differ from Dutch or global distributions. However, Surinam-Dutch mothers appeared to be more anxious about child-rearing than Dutch mothers. Surinam-Dutch mothers who had recently arrived in Holland tended to show less responsiveness, and were more anxious about child-rearing than Surinam-Dutch mothers who had immigrated several years ago. These data may reflect strains that arise from the transition from one culture to another.

A “questionnaire” without questions was given to 175 first-year students. It is assumed that in such an ambiguous situation, the influence of response style is maximal. The students tended to prefer the more positively formulated or less extreme categories. These response styles, however, did not seem to influence answers to meaningful questions from an attitude scale.

In this study, the Adult Attachment Interview (AAI) was applied in The Netherlands, to test certain aspects of its validity, and to provide information about its relation to toddlers' socio-emotional adaptation. In the second year of life, a sample of 80 infants were seen with their father, mother, and professional caregiver in the Strange Situation procedure, and in a free-play situation to assess caregivers' sensitivity. Two years later, 68 children participated in a follow-up study, involving mothers, fathers, and professional caregivers. Parents were interviewed with the AAI, and completed the Parental Bonding Instrument that measures attachment experiences in childhood. Parents also completed the Nijmegen-California Q-sort, to measure their children's ego-resilience and ego-control. Professional caregivers rated children's sociability in pre-school using the Pre-School Behavior Inventory.As predicted the AAI and the Parental Bonding Instrument were related. Only the AAI, however, yielded classifications that corresponded with the quality of infant-parent attachment. Furthermore, AAI classifications for mothers were related to maternal sensitivity: Secure mothers are more sensitive to their daughters than insecure mothers, but for boys this was not true. In addition, AAI classifications for parents were related to their children's socio-emotional development in the pre-school years. Secure mothers have children with more ego-resilience and less ego-undercontrol. Dismissing fathers have children who are rated as more aggressive, less social, and less timid than secure or preoccupied fathers. The AAI appears to be a promising instrument for measuring parental state of mind with respect to attachment relationships in a variety of natural settings.

ABSTRACTBackground: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved–disorganized attachment (Ud) is another transdiagnostic risk factor that may be relevant to explain differences in patient characteristics within diagnostic classifications.Objective: In the current study, we examined unique relations of resting-state functional connectivity (RSFC) with Ud and GPF.Method: RSFC data were collected from a mixed group of adolescents (N = 74) with and without psychiatric disorder, as part of the Emotional Pathways’ Imaging Study in Clinical Adolescents (EPISCA) study. Ud was measured using the Adult Attachment Interview (AAI). Associations between Ud, GPF, and RSFC of the amygdala and dorsal anterior cingulate cortex (dACC) and with amygdala–medial frontal connectivity were examined.Results: Ud was positively associated with greater functional connectivity between the left amygdala and the left lateral occipital cortex, precuneus, and superior parietal lobule. Furthermore, Ud was negatively associated with left amygdala–medial frontal cortex connectivity. GPF was not significantly associated with dACC or amygdala connectivity.Conclusions: Atypical amygdala connectivity may reflect a vulnerability factor rather than a biomarker of psychopathology. The unique association of Ud and amygdala RSFC, adjusted for a GPF, across participants with and without various classifications of psychopathology illustrates that dimensional approaches based on the AAI may complement psychiatric classifications in clinical research and practice.