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
The development of social-cognitive abilities in infancy is subject to an intricate interaction between maturation of neural systems and environmental input. We investigated the role of infants’... Show moreThe development of social-cognitive abilities in infancy is subject to an intricate interaction between maturation of neural systems and environmental input. We investigated the role of infants’ attachment relationship quality in shaping infants’ neural responses to observed social interactions. One-hundred thirty 10-month-old infants participated in an EEG session while they watched animations involving a distressing separation event that ended with either comforting or ignoring behavior. Frontal asymmetry (FA) in the alpha range - which is indicative of approach-withdrawal tendencies - was measured with EEG. Attachment quality was assessed using the Strange Situation procedure at 12 months. Overall, infants with disorganized attachment showed a lack of right-sided – withdrawal related – FA compared to secure and insecure infants. Furthermore, only avoidant infants exhibited reduced right-sided FA responses following the separation. Contrary to our expectations, the type of response (comforting vs. ignoring) did not elicit differences in FA patterns, and attachment quality did not moderate the effects of the type of response on frontal asymmetry. Implications for research on attachment-related biases in social information processing and on the neural underpinnings of prosocial behaviors are discussed. 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
Meulen, M. van der; Wierenga, L.M.; Achterberg, M.; Drenth, N; IJzendoorn, M.H. van; Crone, E.A.M. 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
Even though Parenting Capacity Assessments (PCAs) are essential for child protection services to support placement decisions for maltreating families, presently no evidence-based PCA protocols are... Show moreEven though Parenting Capacity Assessments (PCAs) are essential for child protection services to support placement decisions for maltreating families, presently no evidence-based PCA protocols are available. In this randomized controlled trial, we tested the quality of an attachment-based PCA protocol based on Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD). We recruited 56 parent-child dyads (M(age)children = 3.48 years) in Dutch family residential clinics that conduct PCAs to support placement decisions. After pretest, families were randomized to receive the Regular Assessment Procedure (RAP) (n= 28), or an additional assessment based on VIPP-SD (n= 28). An immediate post-test and a 10-month follow-up were conducted. Multilevel models showed that therapists felt equally confident about their recommendations regarding child placement for both groups and that they equally often modified their initial placement recommendations. Moreover, children in the VIPP-SD group did not show fewer behavior problems and did not experience recurring child maltreatment less often than children in the RAP group. Thus, we found no evidence that PCAs incorporating the VIPP-SD protocol outperformed PCAs as usual. We discuss possible explanations why in the current study VIPP-SD did not seem to add to the quality of the RAP. Show less
Even though Parenting Capacity Assessments (PCAs) are essential for child protection services to support placement decisions for maltreating families, presently no evidence-based PCA protocols are... Show moreEven though Parenting Capacity Assessments (PCAs) are essential for child protection services to support placement decisions for maltreating families, presently no evidence-based PCA protocols are available. In this randomized controlled trial, we tested the quality of an attachment-based PCA protocol based on Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD). We recruited 56 parent-child dyads (M(age)children = 3.48 years) in Dutch family residential clinics that conduct PCAs to support placement decisions. After pretest, families were randomized to receive the Regular Assessment Procedure (RAP) (n= 28), or an additional assessment based on VIPP-SD (n= 28). An immediate post-test and a 10-month follow-up were conducted. Multilevel models showed that therapists felt equally confident about their recommendations regarding child placement for both groups and that they equally often modified their initial placement recommendations. Moreover, children in the VIPP-SD group did not show fewer behavior problems and did not experience recurring child maltreatment less often than children in the RAP group. Thus, we found no evidence that PCAs incorporating the VIPP-SD protocol outperformed PCAs as usual. We discuss possible explanations why in the current study VIPP-SD did not seem to add to the quality of the RAP. Show less
Buisman, R.S.M.; Pittner, K.; Tollenaar, M.S.; Lindenberg, J.; Berg, L.J.M. van den; Compier, H.C.G.; ... ; IJzendoorn, M.H. van 2020
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... Show moreDecisions 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. 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
Meulen, M. van der; Steinbeis, N.A.J.; Achterberg, M.; IJzendoorn, M.H. van; Crone, E.A.M. 2018
Experiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent... Show moreExperiencing and observing social exclusion and inclusion, as well as prosocial behavior, are important aspects of social relationships in childhood. However, it is currently unknown to what extent these processes and their neural correlates differ in heritability. We investigated influences of genetics and environment on experiencing social exclusion and compensating for social exclusion of others with the Prosocial Cyberball Game using fMRI in a twin sample (aged 7–9; N = 500). Neuroimaging analyses (N = 283) revealed that experiencing possible self-exclusion resulted in activity in inferior frontal gyrus and medial prefrontal cortex, which was influenced by genetics and unique environment. Experiencing self-inclusion was associated with activity in anterior cingulate cortex, insula and striatum, but this was not significantly explained by genetics or shared environment. We found that children show prosocial compensating behavior when observing social exclusion. Prosocial compensating behavior was associated with activity in posterior cingulate cortex/precuneus, and showed unique environmental effects or measurement error at both behavioral and neural level. Together, these findings show that in children neural activation for experiencing possible self-exclusion and self-inclusion, and for displaying prosocial compensating behavior, is accounted for by unique environmental factors and measurement error, with a small genetic effect on possible self-exclusion. Show less
Achterberg, M.; Bakermans, M.J.; IJzendoorn, M.H. van; Meulen, M. van der; Tottenham, N.; Crone, E.A.M. 2018
Connectivity between limbic/subcortical and prefrontal-cortical brain regions develops considerably across childhood, but less is known about the heritability of these networks at this age. We... Show moreConnectivity between limbic/subcortical and prefrontal-cortical brain regions develops considerably across childhood, but less is known about the heritability of these networks at this age. We tested the heritability of limbic/subcortical-cortical and limbic/subcortical-subcortical functional brain connectivity in 7- to 9-year-old twins (N = 220), focusing on two key limbic/subcortical structures: the ventral striatum and the amygdala, given their combined influence on changing incentivised behavior during childhood and adolescence. Whole brain analyses with ventral striatum (VS) and amygdala as seeds in genetically independent groups showed replicable functional connectivity patterns. The behavioral genetic analyses revealed that in general VS and amygdala connectivity showed distinct influences of genetics and environment. VS-prefrontal cortex connections were best described by genetic and unique environmental factors (the latter including measurement error), whereas amygdala-prefrontal cortex connectivity was mainly explained by environmental influences. Similarities were also found: connectivity between both the VS and amygdala and ventral anterior cingulate cortex (vACC) showed influences of shared environment, while connectivity with the orbitofrontal cortex (OFC) showed heritability. These findings may inform future interventions that target behavioral control and emotion regulation, by taking into account genetic dispositions as well as shared and unique environmental factors such as child rearing. Show less
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... Show moreRejection 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. Show less
This study aims to explore possible risk factors for child maltreatment in Vietnam by investigating the association of child and family factors with different types of child maltreatment (i.e.,... Show moreThis study aims to explore possible risk factors for child maltreatment in Vietnam by investigating the association of child and family factors with different types of child maltreatment (i.e., sexual abuse, physical abuse, emotional abuse, witnessing parental conflict, and neglect) and the occurrence of multiple types of child maltreatment. Cross-sectional data of 1,851 secondary and high school students aged 12 to 17 years (47.3% boys) in four provinces of Northern Vietnam were obtained using self-report questionnaires. Results indicated that the likelihood of emotional abuse, witnessing parental conflict, and experiencing multiple types of child maltreatment during lifetime increased with age. Boys had a higher risk than girls on lifetime sexual abuse, and past year and lifetime physical abuse. Living in a single parent family was the risk factor related to most types of child maltreatment including lifetime sexual abuse, neglect, and multiple types of child maltreatment, and both past year and lifetime witnessing parental conflict. Interestingly, low socioeconomic status (SES) and parental unemployment were associated with a decreased risk on experiencing emotional abuse in the past year and during lifetime, respectively. “Tiger parenting,” a parenting style observed frequently in East Asian parents, may be more common in families with high SES and might explain this finding. This study highlights the importance of prioritizing single parent families in parenting programs and implementing child maltreatment interventions early because of the risk on child maltreatment increased with age. More research on emotional abuse and “Tiger parenting” in Vietnam could clarify the association of emotional abuse with high SES and parental employment. Finally, the underlying mechanisms of the risk factors in Vietnam should be studied more to inform interventions. Show less
