Investigating default mode network connectivity disruption in children of mothers with depression.

BACKGROUND: Exposure to maternal major depressive disorder (MDD) bears long-term negative consequences for children's well-being; to date, no research has examined how exposure at different stages of development differentially affects brain functioning. AIMS: Utilising a unique cohort followed from birth to preadolescence, we examined the effects of early versus later maternal MDD on default mode network (DMN) connectivity. METHOD: Maternal depression was assessed at birth and ages 6 months, 9 months, 6 years and 10 years, to form three groups: children of mothers with consistent depression from birth to 6 years of age, which resolved by 10 years of age; children of mothers without depression; and children of mothers who were diagnosed with MDD in late childhood. In preadolescence, we used magnetoencephalography and focused on theta rhythms, which characterise the developing brain. RESULTS: Maternal MDD was associated with disrupted DMN connectivity in an exposure-specific manner. Early maternal MDD decreased child connectivity, presenting a profile typical of early trauma or chronic adversity. In contrast, later maternal MDD was linked with tighter connectivity, a pattern characteristic of adult depression. Aberrant DMN connectivity was predicted by intrusive mothering in infancy and lower mother-child reciprocity and child empathy in late childhood, highlighting the role of deficient caregiving and compromised socio-emotional competencies in DMN dysfunction. CONCLUSIONS: The findings pinpoint the distinct effects of early versus later maternal MDD on the DMN, a core network sustaining self-related processes. Results emphasise that research on the influence of early adversity on the developing brain should consider the developmental stage in which the adversity occured.

Testosterone, oxytocin, and the development of human parental care.

The steroid testosterone (T) and neuropeptide oxytocin (OT) have each been implicated in the development of parental care in humans and animals, yet very little research addressed the interaction between these hormones at the transition to parenthood in mothers and fathers. One hundred and sixty mothers and fathers (80 couples) were visited 1 and 6months after the birth of their first child, plasma OT and T were assayed at each time-point, and interactions between each parent and the infant were observed and micro-coded for two key parental behaviors; affectionate touch and parent-infant synchrony. T showed gender-specific effects. While paternal T was individually stable across the first six months of parenting and predicted lower father-infant synchrony, maternal T was neither stable nor predictive of maternal behavior. An interaction of OT and T showed that T has complex modulatory effects on the relations of OT and parenting. Slope analysis revealed that among fathers, only when T was high (+1SD), negative associations emerged between OT and father affectionate touch. In contrast, among mothers, the context of high T was related to a positive association between OT and maternal touch. Our findings, the first to test the interaction of OT and T in relation to observed maternal behavior, underscore the need for much further research on the complex bidirectional effects of steroid and neuropeptide systems on human mothering and fathering.

Mother-child adrenocortical synchrony; Moderation by dyadic relational behavior.

Mother-child adrenocortical synchrony, the coupling of cortisol (CT) secretion in mother and child, has been associated with shared parent-child experiences and maladaptive familial contexts. Yet, few studies tested adrenocortical synchrony in diurnal CT patterns. Guided by the bio-behavioral synchrony model, we examined whether mother-child relational behavior and maternal psychopathology may moderate the degree of concordance between mother and child's diurnal CT. Ninety-seven mothers and their six-year old children participated in two groups; mothers diagnosed with major depression disorder (N=28) and non-depressed controls (N=69). Mother-child interactions were observed and coded for dyadic reciprocity and dyadic tension and diurnal cortisol was collected from mother and child over two consecutive weekend days. Concordance between maternal and child's diurnal CT was found, significant above and beyond time of measurement. Maternal depression, while associated with attenuated child diurnal CT variability, was unrelated to adrenocortical synchrony. Higher child diurnal CT production predicted a stronger linkage between maternal and child's diurnal CT, suggesting that greater child physiological stress is associated with increased susceptibility to the influences of maternal stress physiology. Mother-child reciprocity was related to lower adrenocortical synchrony. Findings suggest that higher adrenocortical synchrony is associated with greater physiological stress and less adaptive dyadic relational patterns. Results raise the possibility that diurnal adrenocortical synchrony taps a unique aspect of HPA-axis functioning whose role in the cross-generational transfer of stress physiology requires further research.

MATERNAL DEPRESSION AND CHILD OXYTOCIN RESPONSE; MODERATION BY MATERNAL OXYTOCIN AND RELATIONAL BEHAVIOR.

BACKGROUND: Maternal postpartum depression (PPD) carries long-term detrimental effects on children's well-being, yet the mechanisms of transmission remain unclear. One possible pathway of vulnerability involves the oxytocinergic (OT) system, which is transferred from mother to child via sensitive caregiving and is disrupted in PPD. METHOD: A large birth cohort (N = 1983) of women were repeatedly assessed for depression from birth to 6 years. Utilizing an extreme case design, two matched cohorts were formed; mothers chronically depressed from birth to 6 years and nondepressed controls (N = 97, depressed = 41, nondepressed; N = 56). At 6 years, mothers and children underwent psychiatric diagnosis, urinary OT was assayed from mother and child before and after social contact, and mother-child interactions were coded. RESULTS: Baseline OT and OT response of mother and child were interrelated and children of depressed mothers showed low baseline OT and attenuated OT response. Child OT response was negatively predicted by maternal depression, child Axis-I psychopathology, maternal expressed negative affect, and child social withdrawal. Interaction effect of maternal baseline OT and depression emerged. Slope analysis indicated that when maternal OT was medium or low, child OT response was negatively impacted by maternal depression. However, when maternal OT was high, child OT was unaffected, suggesting that maternal OT functionality buffers the effects of depression on the child. CONCLUSION: Results suggest involvement of the OT system in the cross-generational transfer of vulnerability, as well as resilience, from depressed mothers to their children. Because the OT system is open to interventions that enhance maternal touch and contact, findings have important implications for targeted early dyadic inventions.

Infant negative reactivity defines the effects of parent-child synchrony on physiological and behavioral regulation of social stress.

How infants shape their own development has puzzled developmentalists for decades. Recent models suggest that infant dispositions, particularly negative reactivity and regulation, affect outcome by determining the extent of parental effects. Here, we used a microanalytic experimental approach and proposed that infants with varying levels of negative reactivity will be differentially impacted by parent-infant synchrony in predicting physiological and behavioral regulation of increasing social stress during an experimental paradigm. One hundred and twenty-two mother-infant dyads (4-6 months) were observed in the face-to-face still face (SF) paradigm and randomly assigned to three experimental conditions: SF with touch, standard SF, and SF with arms' restraint. Mother-infant synchrony and infant negative reactivity were observed at baseline, and three mechanisms of behavior regulation were microcoded; distress, disengagement, and social regulation. Respiratory sinus arrhythmia baseline, reactivity, and recovery were quantified. Structural equation modeling provided support for our hypothesis. For physiological regulation, infants high in negative reactivity receiving high mother-infant synchrony showed greater vagal withdrawal, which in turn predicted comparable levels of vagal recovery to that of nonreactive infants. In behavioral regulation, only infants low in negative reactivity who received high synchrony were able to regulate stress by employing social engagement cues during the SF phase. Distress was reduced only among calm infants to highly synchronous mothers, and disengagement was lowest among highly reactive infants experiencing high mother-infant synchrony. Findings chart two pathways by which synchrony may bolster regulation in infants of high and low reactivity. Among low reactive infants, synchrony builds a social repertoire for handling interpersonal stress, whereas in highly reactive infants, it constructs a platform for repeated reparation of momentary interactive "failures" and reduces the natural tendency of stressed infants to disengage from source of distress. Implications for the construction of synchrony-focused interventions targeting infants of varying dispositions are discussed.

Exposure to early and persistent maternal depression impairs the neural basis of attachment in preadolescence.

Maternal depression increases child vulnerability to psychopathology, loneliness, and social maladjustment; yet, its long-term effects on the social brain are unknown. In this prospective longitudinal study we examined the impact of early and persistent maternal depression on the neural basis of attachment in preadolescence. A community cohort was followed in two groups; children exposed to maternal depression from birth to 6 years and healthy controls. At 9 months and 6 years, mother-child interactions were coded for maternal sensitivity and affect synchrony and salivary oxytocin levels were assessed at 6 years. At preadolescence (11-13 years), children underwent magnetoencephalography (MEG) while exposed to own versus unfamiliar mother-child interaction. Own interaction elicited greater response in beta- and gamma-band oscillations across a wide cluster in temporal and insular cortices, including the Superior Temporal Sulcus, Superior Temporal Gyrus, Inferior Temporal Gyrus, and insula. Beta activations were predicted by maternal sensitivity across early childhood and gamma by affect synchrony. Oxytocin was related to beta response to social cues. Maternal depression impacted child's brain response in two ways. First, maternal depression significantly increased the prevalence of child affective disorder and such children showed no neural differentiation between attachment and non-attachment stimuli. Second, maternal depression decreased maternal sensitivity, affect synchrony, and child oxytocin across early childhood and these were longitudinally associated with aberrant neural response to attachment-specific and social-general cues in preadolescence. Our findings are the first to describe mechanisms by which maternal depression impairs the neural basis of attachment at the transition to adolescence and advocate the need for relationship-focused early interventions.

A social neuroscience approach to conflict resolution: Dialogue intervention to Israeli and Palestinian youth impacts oxytocin and empathy.

The rapid increase in terror-related activities, shift of battlefield into civilian locations, and participation of youth in acts of violence underscore the need to find novel frameworks for youth interventions. Building on the Israeli-Palestinian conflict and social neuroscience models we developed an eight-week dialogue group-intervention for youth growing up amidst intractable conflict. Eighty-eight Israeli-Jewish and Arab-Palestinian adolescents (16-18years) were randomly assigned to intervention or control groups. Before (T1) and after (T2) intervention, one-on-one conflict interaction with outgroup member were videotaped, oxytocin levels assayed, attitudes self-reported, and youth interviewed regarding national conflict. We tested the hypothesis that dialogue intervention would enhance empathic behavior and increase oxytocin levels following interaction with outgroup member. Intervention increased youth perspective-taking on national conflict. Oxytocin increased from T1 to T2 only for adolescents undergoing intervention who improved perspective taking in the process. Structural equation modelling charted three pathways to behavioral empathy toward outgroup member at T2; via endogenous oxytocin, empathic cognitions, and dialogue intervention; however, an alternative model without the intervention arm was non-significant. Our findings highlight the important role of empathy in programs for inter-group reconciliation and support evolutionary models on the precarious balance between the neurobiology of affiliation and the neurobiology of outgroup derogation.

Child brain exhibits a multi-rhythmic response to attachment cues.

Research on the human parental brain implicated brain networks involved in simulation, mentalization and emotion processing and indicated that stimuli of own parent-child interaction elicit greater integration among networks supporting attachment. Here, we examined children's neural activation while viewing own parent-child interactions and asked whether similar networks activate when children are exposed to attachment stimuli. Sixty-five 11-year-old children underwent magnetoencephalography (MEG) while observing own vs unfamiliar mother-child interaction. Own mother-child interactions elicited a greater neural response across distributed brain areas including alpha suppression in posterior regions, theta enhancement in the fusiform gyrus and beta- and gamma-band oscillations across a wide cluster in the right temporal cortex, comprising the superior temporal sulcus/superior temporal gyrus and insula. Theta and gamma activations were associated with the degree of mother-child social synchrony in the home ecology. Findings from this exploratory study are the first to show activations in children that are similar to previous findings in parents and comparable associations between social synchrony and gamma oscillations in temporal regions. Results indicate that attachment stimuli elicit a strong neural response in children that spreads across a wide range of oscillations, underscoring the considerable neural resources allocated to this fundamental, survival-related cue.

Maturation of Pain Empathy from Child to Adult Shifts from Single to Multiple Neural Rhythms to Support Interoceptive Representations.

While empathy to the pain of conspecific is evolutionary-ancient and is observed in rodents and in primates, it also integrates higher-order affective representations. Yet, it is unclear whether human empathy for pain is inborn or matures during development and what neural processes underpin its maturation. Using magnetoencephalography, we monitored the brain response of children, adolescents, and adults (n = 209) to others' pain, testing the shift from childhood to adult functioning. Results indicate that children's vicarious empathy for pain operates via rudimentary sensory predictions involving alpha oscillations in somatosensory cortex, while adults' response recruits advanced mechanisms of updating sensory predictions and activating affective empathy in viceromotor cortex via higher-level representations involving beta- and gamma-band activity. Our findings suggest that full-blown empathy to others' pain emerges only in adulthood and involves a shift from sensory self-based to interoceptive other-focused mechanisms that support human altruism, maintain self-other differentiation, modulate feedback to monitor other's state, and activate a plan of action to alleviate other's suffering.

Maternal Depression Across the First Years of Life Impacts the Neural Basis of Empathy in Preadolescence.

OBJECTIVE: Exposure to maternal depression across the first years of life markedly increases children's susceptibility to psychopathology, yet no study has tested its effects on the maturation of children's social brain. METHOD: Using a birth cohort of mothers with no contextual risk (N = 1,983), families were followed at 7 time points from birth to 11 years and repeatedly assessed for maternal depression across the first 6 years to form 2 cohorts: mothers continuously depressed from birth to 6 years and controls without depression. At 11 years of age, children's (n = 72; depressed, n = 27; nondepressed, n = 45) brain response to others' pain was measured by magnetoencephalography. RESULTS: Preadolescents displayed a unique oscillatory pattern with higher alpha power to pain versus no pain expressing as alpha rebound, not alpha suppression, at a late time window (1,100-1,300 ms post-stimulus) in the supplementary motor area. This suggests that top-down processing in areas of the pain matrix can underpin the maturation of vicarious empathy. Children of mothers with depression showed enhanced alpha rebound to pain in the right posterior superior temporal gyrus, which was unrelated to emotion detection abilities, pointing to decreased late processing of others' overwhelming experiences in socio-cognitive areas. Alpha power in the posterior superior temporal gyrus was predicted by higher maternal intrusiveness and lower synchrony across early childhood. CONCLUSION: These findings, from the first study to examine maternal depression and early caregiving as long-term predictors of children's neural empathic response, pinpoint a decrease in top-down socio-cognitive mechanisms as potential pathways for the cross-generational transfer of vulnerability from mothers with depression to their offspring and highlight the need for early interventions focused on enhancing maternal attunement.

Oxytocin Pathway Genes: Evolutionary Ancient System Impacting on Human Affiliation, Sociality, and Psychopathology.

Oxytocin (OT), a nonapeptide signaling molecule originating from an ancestral peptide, appears in different variants across all vertebrate and several invertebrate species. Throughout animal evolution, neuropeptidergic signaling has been adapted by organisms for regulating response to rapidly changing environments. The family of OT-like molecules affects both peripheral tissues implicated in reproduction, homeostasis, and energy balance, as well as neuromodulation of social behavior, stress regulation, and associative learning in species ranging from nematodes to humans. After describing the OT-signaling pathway, we review research on the three genes most extensively studied in humans: the OT receptor (OXTR), the structural gene for OT (OXT/neurophysin-I), and CD38. Consistent with the notion that sociality should be studied from the perspective of social life at the species level, we address human social functions in relation to OT-pathway genes, including parenting, empathy, and using social relationships to manage stress. We then describe associations between OT-pathway genes with psychopathologies involving social dysfunctions such as autism, depression, or schizophrenia. Human research particularly underscored the involvement of two OXTR single nucleotide polymorphisms (rs53576, rs2254298) with fewer studies focusing on other OXTR (rs7632287, rs1042778, rs2268494, rs2268490), OXT (rs2740210, rs4813627, rs4813625), and CD38 (rs3796863, rs6449197) single nucleotide polymorphisms. Overall, studies provide evidence for the involvement of OT-pathway genes in human social functions but also suggest that factors such as gender, culture, and early environment often confound attempts to replicate first findings. We conclude by discussing epigenetics, conceptual implications within an evolutionary perspective, and future directions, especially the need to refine phenotypes, carefully characterize early environments, and integrate observations of social behavior across ecological contexts.

Maternal depression across the first years of life compromises child psychosocial adjustment; relations to child HPA-axis functioning.

Maternal depression across the first years of life negatively impacts children's development. One pathway of vulnerability may involve functioning of the hypothalamic-pituitary-adrenal (HPA) axis. We utilize a community cohort of 1983 women with no comorbid risk repeatedly assessed for depression from birth to six years to form two groups; chronically depressed (N=40) and non-depressed (N=91) women. At six years, mother and child underwent psychiatric diagnosis, child salivary cortisol (CT) was assessed three times during a home-visit, mother-child interaction was videotaped, and child empathy was coded from behavioral paradigms. Latent Growth curve Model using Structural Equation Modeling (SEM) estimated the links between maternal depression and mother's negative parenting and three child outcomes; psychopathology, social withdrawal, and empathy as related to child CT baseline and variability. Depressed mothers displayed more negative parenting and their children showed more Axis-I psychopathology and social withdrawal. SEM analysis revealed that maternal depression was associated with reduced CT variability, which predicted higher child psychopathology and social withdrawal. Whereas all children exhibited similar initial levels of CT, children of controls reduced CT levels over time while children of depressed mothers maintained high, non-flexible levels. Mother negativity was related to lower initial CT levels, which predicted decreased empathy. Findings suggest that chronic maternal depression may compromise children's social-emotional adjustment by diminishing HPA-system flexibility as well as limiting the mother's capacity to provide attuned and predictable caregiving.