Ijzendoorn, M.H. van

Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal (Article)

2013-02-28T00:00:00Z

The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds.

The generation R study: A review of design, findings to date, and a study of the 5-HTTLPR by environmental interaction from fetal life onward (Article)

2012-11-01T00:00:00Z

Objective: First, we give an overview of child psychiatric research in the Generation R Study, a population-based cohort from fetal life forward. Second, we examine within Generation R whether the functional polymorphism (5-HTTLPR) in the promoter of the serotonin transporter gene interacts with prenatal maternal chronic difficulties, prenatal maternal anxiety or postnatal maternal anxiety to influence child emotional development. Method: A total of 2,136 northern European children were genotyped for 5-HTTLPR and rs25531. Mothers reported chronic difficulties and anxiety symptoms at 20 weeks' pregnancy and when the child was 3 years old. Child emotion recognition was observed at 3 years, and child emotional problems were assessed with the CBCL/1-5 at 5 years. Results: There were consistent main effects of maternal difficulties and anxiety on child emotional problems, but no main effect of 5-HTTLPR. Moreover, children with the s allele were at increased risk for emotional problems if their mothers reported prenatal anxiety symptoms (β = 2.02, p <.001) or postnatal anxiety symptoms (β = 1.64, p < 0.001). Also, in children of mothers with prenatal anxiety symptoms, the s allele was associated with less accurate emotion-matching (β = -0.11, p =.004). Conclusions: This population-based study shows that vulnerability due to 5-HTTLPR is not specific for certain adverse exposures or severe events, but suggests that the small effects of gene-environment interaction on emotional development become manifest early in life.

Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior (Article)

2012-10-01T00:00:00Z

Prenatal maternal psychopathology affects child development, but some children seem more vulnerable than others. Genetic variance in hypothalamic-pituitary-adrenal axis genes may influence the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems. This hypothesis was tested in the Generation R Study, a population-based cohort from fetal life onward. In total, 1727 children of Northern European descent and their mothers participated in this study and were genotyped for variants in the glucocorticoid receptor (GR) gene (rs6189/rs6190, rs10052957, rs41423247, rs6195, and rs6198) and the FK506-binding protein 5 (FKBP5) gene (rs1360780). Prenatal maternal psychological symptoms were assessed at 20 weeks pregnancy and child behavior was assessed by both parents at 3 years. In a subsample of 331 children, data about cortisol reactivity were available. Based on power calculations, only those genetic variants with sufficient minor allele frequencies (rs41423247, rs10052957, and rs1360780) were included in the interaction analyses. We found that variation in GR at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems (beta 0.41, SE 0.16, p0.009). This prenatal interaction effect was independent of mother's genotype and maternal postnatal psychopathology, and not found for prenatal psychological symptoms of the father. Moreover, the interaction between rs41423247 and prenatal psychological symptoms was also associated with decreased child cortisol reactivity (beta 2.30, p-value 0.05). These findings emphasize the potential effect of prenatal gene-environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems.

Variation in the glucocorticoid receptor gene at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child cortisol reactivity and behavior (Article)

2012-10-01T00:00:00Z

Dopaminergic, serotonergic, and oxytonergic candidate genes associated with infant attachment security and disorganization? in search of main and interaction effects (Article)

2011-12-01T00:00:00Z

Background and methods: In two birth cohort studies with genetic, sensitive parenting, and attachment data of more than 1,000 infants in total, we tested main and interaction effects of candidate genes involved in the dopamine, serotonin, and oxytocin systems (DRD4, DRD2, COMT, 5-HTT, OXTR) on attachment security and disorganization. Parenting was assessed using observational rating scales for parental sensitivity (Ainsworth, Bell, & Stayton, 1974), and infant attachment was assessed with the Strange Situation Procedure. Results: We found no consistent additive genetic associations for attachment security and attachment disorganization. However, specific tests revealed evidence for a codominant risk model for COMT Val158Met, consistent across both samples. Children with the Val/Met genotype showed higher disorganization scores (combined effect size d =.22, CI =.10-.34, p <.001). Gene-by-environment interaction effects were not replicable across the two samples. Conclusions: This unexpected finding might be explained by a broader range of plasticity in heterozygotes, which may increase susceptibility to environmental influences or to dysregulation of emotional arousal. This study is unique in combining the two largest attachment cohorts with molecular genetic and observed rearing environment data to date.

Oxytocin receptor gene associated with the efficiency of social auditory processing (Article)

2011-12-01T00:00:00Z

Oxytocin has been shown to facilitate social aspects of sensory processing, thereby enhancing social communicative behaviors and empathy. Here we report that compared to the AA/AG genotypes, the presumably more efficient GG genotype of an oxytocin receptor gene polymorphism (OXTR rs53576) that has previously been associated with increased sensitivity of social processing is related to less self-reported difficulty in hearing and understanding people when there is background noise. The present result extends associations between oxytocin and social processing to the auditory and vocal domain. We discuss the relevance of our findings for autistic spectrum disorders (ASD), as ASD seems related to specific impairments in the orienting to, and selection of speech sounds from background noise, and some social processing impairments in patients with ASD have been found responsive to oxytocin treatment.

The association between parenting and attachment security is moderated by a polymorphism in the mineralocorticoid receptor gene: Evidence for differential susceptibility (Article)

2011-09-01T00:00:00Z

Maternal sensitive responsiveness and extreme insensitivity only partly explain the variance in attachment security. Differences in attachment security may well be rooted in the interplay of genetic variations and environmental factors. The association between parenting (observed sensitive responsiveness and extreme insensitivity) and attachment security (assessed with the Strange Situation Procedure) was hypothesized to be moderated by genes involved in the regulation of the stress response: the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) genes. A significant G. × E interaction was found: infants carrying the minor MR allele (G) were significantly more securely attached if their mothers showed more sensitive responsiveness and significantly less securely attached if their mothers showed more extremely insensitive behaviors. These associations were not significant for carriers of the AA genotype of MR. Findings are discussed from a differential susceptibility perspective.

Oxytocin modulates amygdala, insula, and inferior frontal gyrus responses to infant crying: A randomized controlled trial (Article)

2011-08-01T00:00:00Z

Background: Oxytocin facilitates parental caregiving and motherinfant 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.

Subcortical structures and the neurobiology of infant attachment disorganization: A longitudinal ultrasound imaging study (Article)

2011-08-01T00:00:00Z

Attachment disorganization in infancy is a risk factor for behavior problems and other psychopathology. Traditionally the role of parental behavior for qualitative differences in early attachment relationships has been emphasized. However, disrupted infant-parent interactions only partly explain attachment disorganization. A complementary focus on child factors such as early differences in the underlying neurobiological systems is needed. We examined whether early structural differences in the gangliothalamic ovoid, comprising the basal ganglia and the thalamus, are involved in the etiology of infant attachment disorganization. Gangliothalamic ovoid diameter was measured by ultrasound in 6-week-old participants of a prospective population-based cohort study. Attachment classification of 629 of these infants was assessed with the strange situation at 14 months of age. Neurobiological differences within the normal range were prospectively associated with attachment disorganization. Infants with a larger gangliothalamic ovoid at 6 weeks had a lower risk of attachment disorganization at 14 months (OR = 0.73 per SD increase in diameter, 95% CI 0.57-0.93, p <.05). Volume of the lateral ventricles as an index of general brain development was not associated with attachment disorganization. These findings provide new insight into the etiology of infant attachment disorganization that may in part be neurodevelopmentally determined.

Differential Susceptibility in Early Literacy Instruction Through Computer Games: The Role of the Dopamine D4 Receptor Gene (DRD4) (Article)

2011-06-01T00:00:00Z

Not every child seems equally susceptible to the same parental, educational, or environmental influences even if cognitive level is similar. This study is the first randomized controlled trial to apply the differential susceptibility paradigm to education in relation to children's genotype and early literacy skills. A randomized pretest-posttest control group design was used to examine the effects of the Intelligent Tutoring System Living Letters. Two intervention groups were created, 1 receiving feedback and 1 completing the program without feedback, and 1 control group. Carriers of the long variant of the dopamine D4 receptor gene (DRD4 7-repeat) profited most from the computer program with positive feedback, whereas they performed at the lowest level of early literacy skills in the absence of such feedback. Our findings suggest that behind modest overall educational intervention effects a strong effect on a subgroup of susceptible children may be hidden. © 2011 The Authors. Journal Compilation

The influence of attachment and temperament on venipuncture distress in 14-month-old infants: The Generation R Study (Article)

2011-04-01T00:00:00Z

Objective: This study examined the effects of attachment and temperament on infant distress during venipuncture. Method: The study was embedded in the Generation R Study, a prospective population-based study. Two different research procedures (i.e., blood sampling and the Ainsworth Strange Situation Procedure) yielded measures of venipuncture distress and attachment security and disorganization in 246 infants aged 14 months. Four temperament traits (distress to limitations, fear, recovery from distress, and sadness) were assessed using the maternally reported Infant Behavior Questionnaire - Revised, at the age of 6 months. Results: There were no differences between mean levels of distress during venipuncture in infants classified as having insecure attachment, but there was a trend for disorganized attachment. The temperament traits were not related to distress. However, children with a disorganized attachment and higher temperamental fear had more venipuncture distress. Conclusion: When different risk factors are present simultaneously, infant distress is heightened.

Serotonin transporter polymorphism moderates effects of prenatal maternal anxiety on infant negative emotionality (Article)

2011-03-15T00:00:00Z

Background: Consistent with the fetal programming hypothesis, effects of maternal prenatal anxiety have been found to predict various measures of infant temperament in the early postnatal period. In recent years, a polymorphism in the serotonin transporter gene (5-HTTLPR) emerged as a moderator of diverse environmental influences on different outcomes, with individuals carrying the short allele being generally more vulnerable to adversity. Methods: We tested whether the association between self-reported maternal anxiety at 20 weeks gestation (Brief Symptom Inventory) and mother-rated infant negative emotionality at 6 months after birth (Infant Behavior Questionnaire-Revised) would be moderated by the 5-HTTLPR in a large Dutch cohort sample (n = 1513). We hypothesized that infants carrying the 5-HTTLPR short allele would be more susceptible and therefore more affected by both low and high prenatal maternal anxiety vis-à-vis negative emotionality than other genotypes. Results: Findings of a significant gene X environment interaction (B = .65, p = .01) were supportive of a vulnerability model, with infants carrying the short allele being more negatively emotional when mothers reported anxiety during pregnancy, whereas there was no difference between genotypes on negative emotionality when maternal anxiety was low. Conclusions: The association between maternal anxiety during pregnancy and negative emotionality in early infancy was significant in infants carrying one or more copies of the short allele but not in those homozygous for the long allele. The 5-HTTLPR short allele might increase vulnerability to adverse environmental influences as early as the fetal period.

FKBP5 and resistant attachment predict cortisol reactivity in infants: Gene-environment interaction (Article)

2010-11-01T00:00:00Z

Quality of the parent-infant attachment relationship influences physiological stress regulation. Genetic factors also contribute to the stress regulatory HPA-axis. Quality of attachment as an index of the rearing environment (measured with the Strange Situation Procedure, SSP), and HPA-axis related SNPs (BclI, rs41423247; TthIIII, rs10052957; GR-9β, rs6198; N363S, rs6195; ER22/23EK, rs6189 and 6190; and FKBP5, rs1360780) were hypothesized to be related to cortisol reactivity in the stressful SSP. In this large population based sample, FKBP5 rs1360780, but not GR haplotype, was related to cortisol reactivity. Moreover, we found a significant interaction effect for insecure-resistant attachment and FKBP5 rs1360780, indicating a double-risk for heightened cortisol reactivity levels in infants with one or two T-alleles of the FKBP5 SNP and an insecure-resistant attachment relationship with their mother. Findings are discussed from the perspective of gene-environment interaction.

Attachment, depression, and cortisol: Deviant patterns in insecure-resistant and disorganized infants (Article)

2010-07-01T00:00:00Z

Both attachment insecurity and maternal depression are thought to affect infants' emotional and physiological regulation. In the current study, Strange Situation Procedure (SSP) attachment classifications, and cortisol stress reactivity and diurnal rhythm were assessed at 14 months in a prospective cohort study of 369 mother-infant dyads. Maternal lifetime depression was diagnosed prenatally using the Composite International Diagnostic Interview (CIDI). Insecure-resistant infants showed the largest increase in cortisol levels from pre-to post-SSP; the effect was even stronger when they had depressive mothers. Disorganized children showed a more flattened diurnal cortisol pattern compared to nondisorganized children. Findings are discussed from the perspective of a cumulative risk model.