Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this... Show moreAttachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. This article is divided into two parts. In the first part, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child's need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration. Show less
Galbally, M.; Watson, S.J.; IJzendoorn, M.H. van; Tharner, A.; Luijk, M.; Kloet, E.R. de; ... ; Lewis, A.J. 2021
Childhood anxiety disorders (CAD) are a common childhood mental disorder and understanding early developmental pathways is key to prevention and early intervention. What is not understood is... Show moreChildhood anxiety disorders (CAD) are a common childhood mental disorder and understanding early developmental pathways is key to prevention and early intervention. What is not understood is whether early life stress predictors of CAD might be both mediated by infant cortisol reactivity and moderated by infant attachment status. To address this question, this exploratory study draws on 190 women recruited in early pregnancy and followed together with their children until 4 years of age. Early life stress is operationalized as maternal depression measured using the Structured Clinical Interview for the DSM, Childhood Trauma Questionnaire, Parenting Stress Index, and antenatal maternal hair cortisol concentrations. Infant cortisol reactivity was measured at 12 months together with the Strange Situation Procedure and CAD assessed at 4 years of age using the Preschool Age Psychiatric Assessment. There was no direct association between attachment classification and CAD. Furthermore, infant cortisol reactivity neither mediated nor attachment moderated the association of early life stress predictors and CAD. However, only for infants with organized attachment classifications, higher maternal antenatal depression, and hair cortisol were associated with a higher risk of CAD. Show less
DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >... Show moreDNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.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. Show less
Dongen, J. van; Hagenbeek, F.A.; Suderman, M.; Roetman, P.J.; Sugden, K.; Chiocchetti, A.G.; ... ; BIOS Consortium 2021
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... Show moreDNA 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 x 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. Show less
DNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently... Show moreDNA methylation (DNAm) is known to play a pivotal role in childhood health and development, but a comprehensive characterization of genome-wide DNAm trajectories across this age period is currently lacking. We have therefore performed a series of epigenome-wide association studies in 5019 blood samples collected at multiple time-points from birth to late adolescence from 2348 participants of two large independent cohorts. DNAm profiles of autosomal CpG sites (CpGs) were generated using the Illumina Infinium HumanMethylation450 BeadChip. Change over time was widespread, observed at over one-half (53%) of CpGs. In most cases, DNAm was decreasing (36% of CpGs). Inter-individual variation in linear trajectories was similarly widespread (27% of CpGs). Evidence for non-linear change and inter-individual variation in non-linear trajectories was somewhat less common (11 and 8% of CpGs, respectively). Very little inter-individual variation in change was explained by sex differences (0.4% of CpGs) even though sex-specific DNAm was observed at 5% of CpGs. DNAm trajectories were distributed non-randomly across the genome. For example, CpGs with decreasing DNAm were enriched in gene bodies and enhancers and were annotated to genes enriched in immune-developmental functions. In contrast, CpGs with increasing DNAm were enriched in promoter regions and annotated to genes enriched in neurodevelopmental functions. These findings depict a methylome undergoing widespread and often non-linear change throughout childhood. They support a developmental role for DNA methylation that extends beyond birth into late adolescence and has implications for understanding life-long health and disease. DNAm trajectories can be visualized at http://epidelta.mrcieu. ac.uk. Show less
Meulen, M. van der; Wierenga, L.M.; Achterberg, M.; Drenth, N.; IJzendoorn, M.H. van; Crone, E.A. 2020
Prosocial behavior and empathy are important aspects of developing social relations in childhood. Prior studies showed protracted structural development of social brain regions associated with... Show moreProsocial behavior and empathy are important aspects of developing social relations in childhood. Prior studies showed protracted structural development of social brain regions associated with prosocial behavior. However, it remains unknown how structure of the social brain is influenced by genetic or environmental factors, and whether overlapping heritability factors explain covariance in structure of the social brain and behavior. The current study examined this hypothesis in a twin sample (aged 7-9-year; N = 512). Bilateral measures of surface area and cortical thickness of the medial prefrontal cortex (mPFC), temporo-parietal junction (TPJ), posterior superior temporal sulcus (pSTS), and precuneus were analyzed. Results showed genetic contributions to surface area and cortical thickness for all brain regions. We found additional shared environmental influences for TPJ, suggesting that this region might be relatively more sensitive to social experiences. Genetic factors also influenced parent-reported prosocial behavior (A = 45%) and empathy (A = 59%). We provided initial evidence that the precuneus shares genetically determined variance with empathy, suggesting a possible small genetic overlap (9%) in brain structure and empathy. These findings show that structure of the social brain and empathy are driven by a combination of genetic and environmental factors, with some factors overlapping for brain structure and behavior. Show less
Abstract Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment... Show moreAbstract Background: 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 with Ud and GPF. Method: Resting state functional connectivity (RSFC) data were collected from a mixed group of adolescents (N =74) with and without psychiatric disorder, part of the Emotional Pathways’ Imaging Study in Clinical Adolescents study. Ud was measured using the Adult Attachment Interview (AAI). Associations between Ud, GPF, and RSFC of the amygdala and 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 connectivity, 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. Keywords: General psychopathology factor; unresolved– disorganized attachment; amygdala; resting-state functional connectivity; dorsal anterior cingulate cortex; medial prefrontal cortex; psychopathology; adolescents Show less
Background: Recent research has identified a general psychopathology factor (GPF), which explains overlap in presentation of psychopathological symptoms. Unresolved-disorganized attachment (Ud) is... Show moreBackground: 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. Show less
Childhood Sexual Abuse related posttraumatic stress disorder (CSA-related PTSD), and anxiety and depressive disorders (clinical depression) have profound though differential impact on adolescent... Show moreChildhood Sexual Abuse related posttraumatic stress disorder (CSA-related PTSD), and anxiety and depressive disorders (clinical depression) have profound though differential impact on adolescent emotion regulation, attention bias and emotional face processing. We hypothesized increased negative attention bias for emotional faces and altered brain functioning in CSA-related PTSD compared to internalizing disorders and healthy controls in a cross-sectional fMRI study using an emotional face processing task in 19 12-20-year-old adolescents with CSA-related PTSD, 26 with internalizing disorders and 26 healthy controls.Outcome measures were reaction times, subjective ratings of emotional faces, and brain activation patterns for whole brain and for regions of interest. Compared to both other groups adolescents with CSA-related PTSD showed significantly slower reaction times and the highest subjective rating of emotional faces. On whole brain and ROI level, no significant group differences were found. Self-reported depressive, posttraumatic or dissociative symptoms were not associated with differences in task-related brain activity. Results support the hypothesis of increased negative attention bias for fearful and neutral faces in CSA-related PTSD versus both other groups. The absence of neural differences might indicate a brain-behavior neuro-imaging gap to be closed by larger and IQ matched samples or more sensitive paradigms to elicit emotion processing. Show less
Although attachment representation is considered to be disturbed in traumatized adolescents, it is not known whether this is specific for trauma, as comparative studies with other clinical groups... Show moreAlthough attachment representation is considered to be disturbed in traumatized adolescents, it is not known whether this is specific for trauma, as comparative studies with other clinical groups are lacking. Therefore, attachment representation was studied by means of the Adult Attachment Interview in adolescents with Childhood Sexual Abuse (CSA) (N = 21), clinical depression (N = 28) and non-clinical controls (N = 28). Coherence of mind and unresolved loss or trauma, as well as the disorganized attachment classification differentiated the CSA group from the clinical depression group and controls, over and above age, IQ, and psychiatric symptomatology. In the current era of sustained criticism on criteria-based classification, this may well carry substantial clinical relevance. If attachment is a general risk or vulnerability factor underlying specific psychopathology, this may guide diagnostic assessment as well as treatment. Show less
Background: Oxytocin facilitates parental caregiving and mother-infant bonding and might be involved in responses to infant crying. Infant crying provides information about the physical status and... Show moreBackground: Oxytocin facilitates parental caregiving and mother-infant bonding and might be involved in responses to infant crying. Infant crying provides information about the physical status and mood of the infant and elicits parental proximity and caregiving. Oxytocin might modulate the activation of brain structures involved in the perception of cry sounds-specifically the insula, the amygdala, and the thalamocingulate circuit-and thereby affect responsiveness to infant crying. Method: In a randomized controlled trial we investigated the influence of intranasally administered oxytocin on neural responses to infant crying with functional magnetic resonance imaging. Blood oxygenation level-dependent responses to infant crying were measured in 21 women who were administered oxytocin and 21 women who were administered a placebo. Results: Induced oxytocin levels reduced, experimentally, activation in the amygdala and increased activation in the insula and inferior frontal gyrus pars triangularis. Conclusions: Our findings suggest that oxytocin promotes responsiveness to infant crying by reducing activation in the neural circuitry for anxiety and aversion and increasing activation in regions involved in empathy. Show less