Current maternal depression associated with worsened children's social outcomes during middle childhood: Exploring the role of positive affect socialization.

BACKGROUND: Maternal depression negatively predicts aspects of the mother-child relationship and social functioning in offspring. This study evaluated interrelations between mothers' depression history and current severity with dynamic indices of positive affect socialization and indices of offspring' social outcomes. METHODS: N = 66 mother-child dyads in which approximately 50 % of mothers had a history of maternal depression were recruited. Children were 6-8 years old and 47.7 % male. Dyads completed a positive interaction task, which was coded for mother and child positive affect. Mothers and children reported on peer functioning and social problems and children reported on the quality of their best friendships at 1-year follow-up. RESULTS: Current level of maternal depression, but not depression history, was related to more social problems and lower best friend relationship quality. Indices of positive affect socialization were not related to history or current levels of maternal depression, or social outcomes, with the exception of maternal depression history predicting greater likelihood of mothers joining their children in expressing positive affect. Exploratory, supplementary analysis revealed that this may be due to treatment history among these mothers. LIMITATIONS: Conclusions should be tempered by the small sample size, which limited the types of analyses that were conducted. CONCLUSION: Results suggest that the effect of maternal depression on aspects of child social outcomes could be specific to current levels. Our data also did not support previously found associations between maternal depression and positive affect socialization. Results suggest positive implications for the effect of treatment for maternal depression for mother-child dynamics.

Adolescents' Hormonal Responses to Social Stress and Associations with Adolescent Social Anxiety and Maternal Comfort: A Preliminary Study.

Both social support and social stress can impact adolescent physiology including hormonal responses during the sensitive transition to adolescence. Social support from parents continues to play an important role in socioemotional development during adolescence. Sources of social support and stress may be particularly impactful for adolescents with social anxiety symptoms. The goal of the current study was to examine whether adolescent social anxiety symptoms and maternal comfort moderated adolescents' hormonal response to social stress and support. We evaluated 47 emotionally healthy 11- to 14-year-old adolescents' cortisol and oxytocin reactivity to social stress and support using a modified version of the Trier Social Stress Test for Adolescents that included a maternal comfort paradigm. Findings demonstrated that adolescents showed significant increases in cortisol and significant decreases in oxytocin following the social stress task. Subsequently, we found that adolescents showed significant decreases in cortisol and increases in oxytocin following the maternal comfort paradigm. Adolescents with greater social anxiety symptoms showed higher levels of cortisol at baseline but greater declines in cortisol response following maternal social support. Social anxiety symptoms were unrelated to oxytocin response to social stress or support. Our findings provide further evidence that mothers play a key role in adolescent regulation of physiological response, particularly if the stressor is consistent with adolescents' anxiety. More specifically, our findings suggest that adolescents with higher social anxiety symptoms show greater sensitivity to maternal social support following social stressors. Encouraging parents to continue to serve as a supportive presence during adolescent distress may be helpful for promoting stress recovery during the vulnerable transition to adolescence.

Mother-child neural synchronization is time linked to mother-child positive affective state matching.

In the first years of life, in which self-regulation occurs via external means, mother-child synchronization of positive affect (PA) facilitates regulation of child homeostatic systems. Mother-child affective synchrony may contribute to mother-child synchronization of neural systems, but limited research has explored this possibility. Participants were 41 healthy mother-child dyads (56% girls; Mage = 24.76 months; s.d. = 8.77 months, Range = 10-42 months). Mothers' and children's brain activities were assessed simultaneously using near-infrared spectroscopy while engaging in dyadic play. Mother and child PA during play were coded separately to characterize periods in which mothers and children (i) matched on high PA, (ii) matched on low/no PA or (iii) showed a mismatch in PA. Models evaluated moment-to-moment correlations between affective matching and neural synchrony in mother-child dyads. Greater positive affective synchrony, in which mother and child showed similarly high levels of PA but not similarly low levels of PA, was related to greater synchrony in medial and lateral frontal and temporoparietal regions. Age moderated associations between mother and child neural activities but only during moments of high PA state matching. Positive, synchronous mother-child interactions may foster greater neural responding in affective and social regions important for self-regulation and interpersonal bonds.

Maternal Response to Positive Affect Moderates the Impact of Familial Risk for Depression on Ventral Striatal Response to Winning Reward in 6- to 8-Year-Old Children.

BACKGROUND: A growing body of research has demonstrated that adolescent offspring of depressed parents show diminished responding in the ventral striatum to reward. More recent work has suggested that altered reward responding may emerge earlier than adolescence in offspring at familial risk for depression, although factors associated with neural alterations in childhood remain poorly understood. METHODS: We tested whether 6- to 8-year-old children, 49% at heightened risk for depression via maternal history, showed altered neural responding to winning reward. We evaluated whether maternal socialization of positive emotion moderated the association between familial risk and child neural response to reward. Participants were 49 children 6 to 8 years of age (24 with a maternal history of recurrent or chronic depression, 25 with no maternal history of any psychiatric disorder). Children underwent functional magnetic resonance imaging while completing the Doors Guessing Task, a widely used reward guessing task. Mothers reported their use of encouraging and dampening responses to child positive affect. RESULTS: Findings demonstrated that children at high familial risk for depression showed lower ventral striatum responding to winning reward relative to low-risk children, but only when mothers used less encouragement or greater dampening responses to their child's positive emotion expressions. CONCLUSIONS: Neural reward alterations in the ventral striatum may emerge earlier than previously thought, as early as 6 to 8 years of age, specifically in the context of maternal discouragement of child positive emotions. Clinical interventions that focus on coaching mothers on how to encourage child positive emotions may be beneficial for supporting child reward-related brain development.

Postpartum Depression Is Associated With Altered Neural Connectivity Between Affective and Mentalizing Regions During Mother-Infant Interactions.

Although there has been growing interest in mood-related neural alterations in women in the initial weeks postpartum, recent work has demonstrated that postpartum depression often lingers for months or years following birth. However, research evaluating the impact of depression on maternal brain function during mother-infant interactions in the late postpartum period is lacking. The current study tested the hypothesis that depressive symptoms at 12-months postpartum are associated with neural alterations in affective and social neural regions, using near-infrared spectroscopy during in vivo mother-infant interactions. Participants were 23 birth mothers of 12-month-old infants (60% boys). While undergoing near-infrared spectroscopy, mothers engaged in an ecologically valid interactive task in which they looked at an age-appropriate book with their infants. Mothers also reported on their depressive symptoms in the past week and were rated on their observed levels of maternal sensitivity during mother-infant play. Greater depressive severity at 12-months postpartum was related to lower connectivity between the right temporoparietal junction and the lateral prefrontal cortex, but greater connectivity between the right temporoparietal junction and anterior medial prefrontal cortex during mother-infant interaction. Given the putative functions of these neural regions within the maternal brain network, our findings suggest that in the context of depression, postpartum mothers' mentalizing about her infants' thoughts and feelings may be related to lower ability to express and regulate her own emotions, but greater ability to engage in emotional bonding with her infant. Future work should explore how connectivity among these regions is associated with longitudinal changes in maternal behavior, especially in the context of changes in mothers' depressive symptoms (e.g., with treatment) over time.

Association of Neural Reward Circuitry Function With Response to Psychotherapy in Youths With Anxiety Disorders.

OBJECTIVE: Identifying neural correlates of response to psychological treatment may inform targets for interventions designed to treat psychiatric disorders. This study examined the extent to which baseline functioning in reward circuitry is associated with response to psychotherapy in youths with anxiety disorders. METHODS: A randomized clinical trial of cognitive-behavioral therapy compared with supportive therapy was conducted in youths with anxiety disorders. Before treatment, 72 youths (9-14 years old) with anxiety disorders and 37 group-matched healthy comparison youths completed a monetary reward functional MRI task. Treatment response was defined categorically as at least a 35% reduction in diagnostician-rated anxiety severity from pre- to posttreatment assessment. Pretreatment neural activation in the striatum and medial prefrontal cortex (mPFC) during monetary wins relative to losses was examined in relation to treatment response. RESULTS: Responders, nonresponders, and healthy youths differed significantly in mPFC activation to rewards versus losses at baseline. Youths with anxiety exhibited higher mPFC activity relative to healthy youths, although this may have been driven by differences in depressive symptoms. Planned comparisons between treatment responders (N=48) and nonresponders (N=24) also revealed greater pretreatment neural activation in a cluster encompassing the subgenual anterior cingulate cortex and nucleus accumbens among responders. CONCLUSIONS: Striatal activation to reward receipt may not differentiate youths with anxiety from healthy youths. However, higher striatal responsivity to rewards may allow youths with anxiety to improve during treatment, potentially through greater engagement in therapy. Function in reward circuitry may guide development of treatments for youths with anxiety.

Adolescent gender differences in neural reactivity to a friend's positive affect and real-world positive experiences in social contexts.

Peers become increasingly important during adolescence, with emerging gender differences in peer relationships associated with distinct behavioral and emotional outcomes. Males tend to socialize in larger peer groups with competitive interactions, whereas females engage in longer bouts of dyadic interaction with more intimacy. To examine gender differences in neural response to ecologically valid displays of positive affect and future social interactions, 52 adolescents (14-18 years old; female = 30) completed a social reward functional magnetic resonance imaging (fMRI) task with videos of a same-gender best friend (BF) or unfamiliar peer (UP) expressing positive (versus neutral) affect. Participants completed ecological momentary assessment of social experiences for two 5-day intervals. Compared with females, males more often reported that their happiest experience in the past hour occurred with class/teammates. Females and males displayed greater fusiform gyrus (FG) activation during BF and UP conditions, respectively (pvoxel<0.0001, pcluster<0.05, family-wise error). Compared with males, females exhibited greater nucleus accumbens (NAcc)-precuneus functional connectivity to BF Positive> UP Positive. An exploratory analysis indicated that the association of male gender with a greater proportion of positive experiences with class/teammates was statistically mediated by greater NAcc-precuneus functional connectivity. Gender differences in positive social experiences may be associated with reward and social cognition networks.

Depression Moderates Maternal Response to Preschoolers' Positive Affect.

Maternal depression is associated with disrupted responsiveness during mother-infant dyadic interactions. Less research has evaluated whether responsivity between mother and offspring is altered in interactions during the preschool years, a period of vast socio-emotional development. In the current study, 72 mothers and preschoolers engaged in a positive emotion-eliciting task, in which they drew and talked about a recent fun experience, and independent coders separately rated mother and child emotion in 10-second intervals. Lagged multilevel models demonstrated that for dyads with currently depressed mothers, but not for healthy mothers or mothers with a past history of depression, greater child positive affect was associated with lower frequency and intensity of mother positive affect 10 seconds later. The effect of mother positive affect on child response was not significant. Findings suggest that the ability to acknowledge, imitate, and elaborate children's positive emotion during early childhood is altered in the context of depression, but that this altered responsiveness may improve with recovery from depression.

Positive affect between close friends: Brain-behavior associations during adolescence.

Identifying the neural correlates of positive interactions between friendship dyads may provide insights into mechanisms associated with adolescent social development. Forty-eight 14- to 18-year-old typically developing adolescents were video-recorded discussing a shared positive event with a close friend and subsequently viewed clips during an fMRI scan of that friend during the interaction and of an unfamiliar peer in a similar interaction. Adolescents also reported on their positive affect in daily life while with friends using ecological momentary assessment. We used multivariate repeated measures models to evaluate how positive affect with friends in the laboratory and in daily life was associated with neural response to friend and stranger positive and neutral clips. Adolescents who exhibited more positive affect when with friends in the laboratory showed less dorsolateral prefrontal cortex to friend positive clips. More positive affect when with friends in daily life was associated with less bilateral anterior insula response to friend positive clips, but greater left anterior insula response to stranger positive clips. Findings provide information on the role of lateral prefrontal cortex and anterior insula in enjoyment of friendships during adolescence.

Differential neural responding to affective stimuli in 6- to 8-year old children at high familial risk for depression: Associations with behavioral reward seeking.

OBJECTIVE: Children of depressed parents are at increased risk for psychopathology. One putative mechanism of risk appears to be altered processing of emotion-related stimuli. Although prior work has evaluated how adolescent offspring of depressed parents may show blunted reward processing compared to low-risk youth, there has been less attention to how young children with this familial history may differ from their peers during middle childhood, a period of critical socio-affective development METHOD: The current study evaluated 56 emotionally healthy 6-to 8-year children who were deemed at high-risk (n = 25) or low-risk (n = 31) for depression based on maternal history of depression. Children completed a behavioral reward seeking task in the laboratory and an fMRI paradigm assessing neural response to happy faces, a social reward. RESULTS: Findings demonstrated that high-risk children showed blunted responding to happy faces in the dorsal striatum compared to low-risk children. Further, lower responding in the dorsal striatum and dorsolateral prefrontal cortex was related to lower behavioral reward seeking, but only in high-risk children. CONCLUSION: Function within neural reward regions may be altered in high-risk offspring as young as 6- to 8-years of age. Further, neural reward responding may be linked to lower behavioral response to obtain reward in these high-risk offspring.

Viable Mice with Extensive Gene Humanization (25-kbp) Created Using Embryonic Stem Cell/Blastocyst and CRISPR/Zygote Injection Approaches.

Here, we describe an expansion of the typical DNA size limitations associated with CRISPR knock-in technology, more specifically, the physical extent to which mouse genomic DNA can be replaced with donor (in this case, human) DNA at an orthologous locus by zygotic injection. Driving our efforts was the desire to create a whole animal model that would replace 17 kilobase pairs (kbp) of the mouse Bcl2l11 gene with the corresponding 25-kbp segment of human BCL2L11, including a conditionally removable segment (2.9-kbp) of intron 2, a cryptic human exon immediately 3' of this, and a native human exon some 20 kbp downstream. Using two methods, we first carried out the replacement by employing a combination of bacterial artificial chromosome recombineering, classic embryonic stem cell (ESC) targeting, dual selection, and recombinase-driven cassette removal (ESC/Blastocyst Approach). Using a unique second method, we employed the same vector (devoid of its selectable marker cassettes), microinjecting it along with redundant single guide RNAs (sgRNAs) and Cas9 mRNA into mouse zygotes (CRISPR/Zygote Approach). In both instances, we were able to achieve humanization of Bcl2l11 to the extent designed, remove all selection cassettes, and demonstrate the functionality of the conditionally removable, loxP-flanked, 2.9-kbp intronic segment.

Temptations of friends: adolescents' neural and behavioral responses to best friends predict risky behavior.

Adolescents are notorious for engaging in risky, reward-motivated behavior, and this behavior occurs most often in response to social reward, typically in the form of peer contexts involving intense positive affect. A combination of greater neural and behavioral sensitivity to peer positive affect may characterize adolescents who are especially likely to engage in risky behaviors. To test this hypothesis, we examined 50 adolescents' reciprocal positive affect and neural response to a personally relevant, ecologically valid pleasant stimulus: positive affect expressed by their best friend during a conversation about past and future rewarding mutual experiences. Participants were typically developing community adolescents (age 14-18 years, 48.6% female), and risky behavior was defined as a factor including domains such as substance use, sexual behavior and suicidality. Adolescents who engaged in more real-life risk-taking behavior exhibited either a combination of high reciprocal positive affect behavior and high response in the left ventrolateral prefrontal cortex-a region associated with impulsive sensation-seeking-or the opposite combination. Behavioral and neural sensitivity to peer influence could combine to contribute to pathways from peer influence to risky behavior, with implications for healthy development.

Prevention of perioperative venous thromboembolism in pediatric patients: Guidelines from the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI).

The Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI) Guidelines Working Group on Thromboprophylaxis in Children has reviewed the literature and where possible provided advice on the care of children in the perioperative period. Areas reviewed include the incidence of perioperative venous thromboembolism (VTE), risk factors, evidence for mechanical and chemical prophylaxis, and complications. Safe practice of regional anesthesia with anticoagulant prophylaxis is detailed. In summary, there are few areas of strong evidence. Routine prophylaxis cannot be recommended for young children. Postpubertal adolescents (approximately 13 years and over) are at a slightly increased risk of VTE and should be assessed for prophylaxis and may warrant intervention if other risk factors are present. However, the incidence of VTE is significantly lower than in the adult population. This special interest review presents a summary and discussion of the key recommendations, a decision-making algorithm and a risk assessment chart. For the full guideline, go to www.apagbi.org.uk/publications/apa-guidelines.

Developmental constraint through negative pleiotropy in the zygomatic arch.

BACKGROUND: Previous analysis suggested that the relative contribution of individual bones to regional skull lengths differ between inbred mouse strains. If the negative correlation of adjacent bone lengths is associated with genetic variation in a heterogeneous population, it would be an example of negative pleiotropy, which occurs when a genetic factor leads to opposite effects in two phenotypes. Confirming negative pleiotropy and determining its basis may reveal important information about the maintenance of overall skull integration and developmental constraint on skull morphology. RESULTS: We identified negative correlations between the lengths of the frontal and parietal bones in the midline cranial vault as well as the zygomatic bone and zygomatic process of the maxilla, which contribute to the zygomatic arch. Through gene association mapping of a large heterogeneous population of Diversity Outbred (DO) mice, we identified a quantitative trait locus on chromosome 17 driving the antagonistic contribution of these two zygomatic arch bones to total zygomatic arch length. Candidate genes in this region were identified and real-time PCR of the maxillary processes of DO founder strain embryos indicated differences in the RNA expression levels for two of the candidate genes, Camkmt and Six2. CONCLUSIONS: A genomic region underlying negative pleiotropy of two zygomatic arch bones was identified, which provides a mechanism for antagonism in component bone lengths while constraining overall zygomatic arch length. This type of mechanism may have led to variation in the contribution of individual bones to the zygomatic arch noted across mammals. Given that similar genetic and developmental mechanisms may underlie negative correlations in other parts of the skull, these results provide an important step toward understanding the developmental basis of evolutionary variation and constraint in skull morphology.

Maternal Affective Expression and Adolescents' Subjective Experience of Positive Affect in Natural Settings.

This study investigated the association between maternal affective expression during laboratory-based interaction tasks and adolescents' experience of positive affect (PA) in natural settings. Participants were 80 healthy adolescents and their mothers. Durations of maternal positive (PA) and negative affective (NA) expressions were observed during a conflict resolution task and a positive event planning interaction task. Ecological momentary assessment (EMA) procedures were employed to assess adolescents' momentary and peak experience of PA in daily life. Results indicated that maternal NA, but not maternal PA, was related to adolescents' EMA-reported PA. Adolescents whose mothers expressed more NA experienced less PA in daily environments. Results suggest that adolescents' exposure to maternal negative affective behavior is associated with adolescents' subjective daily well-being.

Postpartum depressive symptoms moderate the link between mothers' neural response to positive faces in reward and social regions and observed caregiving.

Postpartum depression may disrupt socio-affective neural circuitry and compromise provision of positive parenting. Although work has evaluated how parental response to negative stimuli is related to caregiving, research is needed to examine how depressive symptoms during the postpartum period may be related to neural response to positive stimuli, especially positive faces, given depression's association with biased processing of positive faces. The current study examined the association between neural response to adult happy faces and observations of maternal caregiving and the moderating role of postpartum depression, in a sample of 18- to 22-year old mothers (n = 70) assessed at 17 weeks (s.d. = 4.7 weeks) postpartum. Positive caregiving was associated with greater precuneus and occipital response to positive faces among mothers with lower depressive symptoms, but not for those with higher symptoms. For mothers with higher depressive symptoms, greater ventral and dorsal striatal response to positive faces was associated with more positive caregiving, whereas the opposite pattern emerged for mothers with lower symptoms. There was no association between negative caregiving and neural response to positive faces or negative faces. Processing of positive stimuli may be an important prognostic target in mothers with depressive symptoms, given its link with healthy caregiving behaviors.

Effect of maternal rumination and disengagement during childhood on offspring neural response to reward in late adolescence.

Maternal rumination is a cognitive-affective trait that could influence offspring's ability to respond flexibly to positive and negative events, depending on the quality of maternal problem-solving behaviors with which rumination co-occurs. As reward circuitry is sensitive to stressors and related to risk for depression, reward circuitry is an appropriate candidate mechanism for how maternal characteristics influence offspring. We evaluated the independent and combined effect of maternal rumination and disengagement on adolescent neural response to reward win and loss. Participants were 122 boys and their mothers from low-income, urban backgrounds followed prospectively in a longitudinal study. The combination of high maternal rumination at child age 6 and high maternal disengagement during problem-solving at child age 10-12 was associated with lower anterior cingulate response to winning reward at age 20, but unrelated to neural response to losing reward. Lower anterior cingulate response to winning reward was associated with fewer anxiety symptoms during late adulthood. Findings suggest that maternal rumination occurring within the context of maternal disengagement during challenging experiences may be related to offspring blunted engagement during positive events. Helping highly ruminative mothers to restructure repetitive negative thoughts and to develop context-appropriate problem-solving behaviors may be important for promoting offspring affective development.

Altered Positive Affect in Clinically Anxious Youth: the Role of Social Context and Anxiety Subtype.

Anxious youth may experience altered positive affect (PA) relative to healthy youth, perhaps because of greater sensitivity to social experiences. Altered PA may be especially evident during the transition to adolescence, a period in which positive social events increase in salience and value. The current study evaluated whether anxious youth show differences in baseline PA, rate of return to baseline, and variability around baseline PA and tested whether these differences would depend on social context and anxiety subtype. Participants were 176 9- to 14-year-old youth, including 130 clinically anxious (with Social Anxiety Disorder, Generalized Anxiety Disorder, and/or Separation Anxiety Disorder) and 46 healthy youth. Youth reported their current PA, peak PA in the past hour, and social context in natural settings using ecological momentary assessment. Hierarchical linear models showed that both socially anxious and other anxious youth showed greater variability of PA relative to healthy youth. Youth with other anxiety disorders showed higher peak PA to a positive event relative to healthy youth. Feeling close to a friend was associated with higher peak PA, especially for socially anxious youth. Socially anxious youth showed significantly lower peak PA relative to both healthy and other anxious youth when interacting with a less close peer, but similar levels to these youth when interacting with a close friend. These findings suggest that clinically anxious youth may more sensitive to positive events and social interactions than healthy youth. Findings provide potential treatment targets for anxious youth, including applying regulatory strategies to positive events.

History of Depression and Frontostriatal Connectivity During Reward Processing in Late Adolescent Boys.

Given that depression in men is associated with risk for seriously adverse consequences, evaluating how putative neural mechanisms of depression-such as reward-related frontostriatal connectivity-may be altered in late adolescent boys with a history of depression is an important research aim. Adolescents and adults with depression have been demonstrated to show blunted striatal response and heightened medial prefrontal cortex (mPFC) activation to winning reward. Function in reward circuits appears to be best understood as coordination of regions within frontostriatal circuitry, and alterations to this circuitry could occur in those with a history of depression. The current study evaluated functional connectivity between the nucleus accumbens and mPFC in a sample of 166 ethnically diverse boys with and without a history of depression. Participants completed an fMRI monetary reward paradigm at age 20. Lifetime history of depression and other psychiatric illnesses was measured prospectively and longitudinally, using structured clinical interviews at 7 time points from ages 8 to 20. Boys with a history of depression showed heightened positive connectivity between the nucleus accumbens and the mPFC relative to boys with no psychiatric history when winning rewards relative to losing rewards. This altered frontostriatal connectivity pattern was also associated with greater number of depressive episodes in the boys' lifetime. History of depression in late adolescent boys may be associated with altered coordination between the nucleus accumbens and mPFC when winning reward. This coordination could reflect oversignaling of the mPFC to dampen typical ventral striatum response or enhance weak ventral striatum response.

Emotion-based preventive intervention: Effectively promoting emotion knowledge and adaptive behavior among at-risk preschoolers.

Effectiveness studies of preschool social-emotional programs are needed in low-income, diverse populations to help promote the well-being of at-risk children. Following an initial program efficacy study 2 years prior, 248 culturally diverse Head Start preschool children participated in the current effectiveness trial and received either the Emotion-Based Prevention Program (EBP) or the I Can Problem Solve (ICPS) intervention. Pre- and postdata collection included direct child assessment, teacher report, parent interview, and independent observations. Teachers implementing the EBP intervention demonstrated good and consistent fidelity to the program. Overall, children in EBP classrooms gained more emotion knowledge and displayed greater decreases in negative emotion expressions and internalizing behaviors across the implementation period as compared to children in ICPS classrooms. In addition, cumulative risk, parental depressive symptoms, and classroom climate significantly moderated treatment effects. For children experiencing more stress or less support, EBP produced more successful outcomes than did ICPS. These results provide evidence of EBP sustainability and program effectiveness, as did previous findings that demonstrated EBP improvements in emotion knowledge, regulation skills, and behavior problems replicated under unsupervised program conditions.