Exploring the role of OXTR gene methylation in attachment development: A longitudinal study.

The current study explored longitudinally whether oxytocin receptor gene methylation (OXTRm) changes moderated the association between parental sensitivity changes and children's attachment changes over three waves. Six hundred six Flemish children (10-12 years, 42.8%-44.8% boys) completed attachment measures and provided salivary OXTRm data on seven CpG sites. Their parents reported their sensitive parenting. Results suggest that OXTRm changes hardly link to attachment (in)security changes after the age of 10. Some support was found for interaction effects between parental sensitivity changes and OXTRm changes on attachment changes over time. Effects suggest that for children with increased OXTRm in the promotor region and decreased methylation in the inhibitor region over time, increased parental sensitivity was associated with increased secure attachment and decreased insecure attachment over time.

Perceived Parental Support and Psychological Control, DNA Methylation, and Loneliness: Longitudinal Associations Across Early Adolescence.

A broad range of factors have been associated with the development of adolescent loneliness. In the family context, a lack of parental support and high levels of parental psychological control have systematically been linked to loneliness. On the biological level, DNA methylation (which is an epigenetic process that suppresses gene expression) is believed to play a role in the development of loneliness. Specifically, high levels of DNA methylation in genes that play an important role in the functioning of the human stress response system are believed to elevate the risk of loneliness. Moreover, DNA methylation levels in these stress-related genes can be influenced by stressful environmental factors, suggesting a potential mediating role of DNA methylation in the association between parenting behaviors and loneliness. The current 3-year longitudinal study is the first study to examine the potential bidirectional longitudinal associations between loneliness, DNA methylation in stress-related genes, and both perceived parental support and psychological control. Furthermore, we explored the potential mediating role of DNA methylation in stress-related genes in the associations between perceived parenting and loneliness. The sample comprised 622 early adolescents (55% girls, Mage T1 = 10.77 years, SDage T1 = 0.48) who were followed from Grade 5 to 7. Parental support, psychological control, and loneliness were assessed annually by adolescent self-report questionnaires and DNA methylation was determined from saliva samples. Cross-Lagged Panel Models (CLPM) revealed that higher levels of loneliness predicted lower perceived parental support and higher perceived psychological control over time, as well as higher DNA methylation in some stress-related genes, that is, the glucocorticoid receptor gene (NR3C1) and the brain-derived neurotrophic factor (BDNF). In addition, higher NR3C1 methylation was predictive of lower perceived parental support and higher psychological control over time. No evidence was found for a mediating role of DNA methylation. Overall, our longitudinal findings challenge the current focus on DNA methylation and parenting behaviors as risk factors for adolescent loneliness. Instead, they suggest that the less considered direction of effects, which implies that loneliness predicts DNA methylation and aspects of parenting such as support and psychological control, should receive greater attention in future research.

Mild daily stress, in interaction with NR3C1 DNA methylation levels, is linked to alterations in the HPA axis and ANS response to acute stress in early adolescents.

BACKGROUND: Daily Hassles (DH) or daily stress - is a mild type of stressor with unique contributions to psychological distress. Yet, most prior studies that investigate the effects of stressful life experiences focus on childhood trauma or on early life stress and little is known about the effects of DH on epigenetic changes in stress system related genes and on the physiological response to social stressors. METHODS: In the present study, conducted among 101 early adolescents (mean age = 11.61; SD = 0.64), we investigated whether Autonomic Nervous System (ANS) (namely heart rate and heart rate variability) and Hypothalamic-Pituitary-Adrenal (HPA) axis functioning (measured as cortisol stress reactivity and recovery) are associated with DNA methylation (DNAm) in the glucocorticoid receptor gene (NR3C1), the level of DH and their interaction. To assess the stress system functioning the TSST protocol was used. RESULTS: Our findings show that higher NR3C1 DNAm in interaction with higher levels of daily hassles, is associated with blunted HPA axis reactivity to psychosocial stress. In addition, higher levels of DH are associated with extended HPA axis stress recovery. In addition, participants with higher NR3C1 DNAm had lower ANS adaptability to stress, specifically lower parasympathetic withdrawal; for heart rate variability this effect was strongest for participants with higher level of DH. CONCLUSIONS: The observation that interaction effects between NR3C1 DNAm levels and daily stress on the functioning of the stress-systems, are already detectable in young adolescents, highlights the importance of early interventions, not only in the case of trauma, but also daily stress. This might help to prevent stress-induced mental and physical disorders later in life.

Cumulative family stress and externalizing problems: Secure base script knowledge as a protective factor.

The current study examined whether secure base script knowledge can buffer against higher concurrent externalizing problems and against relative increases in externalizing problems associated with cumulative family stress. We conducted a one-year longitudinal study with two waves between 2017 and 2019 in which 272 Dutch-speaking Western European children from Flanders (47.8% boys, M age = 10.20 , SD age = 0.60 ) participated. Secure base script knowledge was associated with lower concurrent externalizing problems (f2  = 0.03). High levels of secure base script knowledge also buffered against relative increases in externalizing problems associated with cumulative family risk (f2  = 0.02). These findings suggest that secure base script knowledge can mitigate the negative effects of a stressful family environment on externalizing problems.

Individual differences in environmental sensitivity at physiological and phenotypic level: Two sides of the same coin?

Young adolescents are hypothesized to differ in their environmental sensitivity, at both phenotypic (i.e., Sensory Processing Sensitivity [SPS]) and physiological (i.e., biological stress response) level. This is the first study that investigated whether individual differences in environmental sensitivity at physiological level could be predicted by individual differences at phenotypic level, as measured with the HSC scale. A total of 101 adolescents (Mage = 11.61, SDage = 0.64) participated in a standardized social stress task (i.e., Trier Social Stress Task-Modified version for children and adolescents (TSST-M)). From baseline to the end of recovery, eight cortisol samples were collected, as well as a continuous measure of Autonomic Nervous System activity. Adolescents reported on SPS and on perceived stress before, during, and after TSST-M. As a follow-up analysis, the quality of the environment, the possible overlap with Neuroticism, and several covariates were considered. Multilevel models were used to investigate within- and between-person differences in stress reactivity across different systems. Results indicate significant individual differences in heart rate, heart rate variability, skin conductance, cortisol, and perceived stress in response to the TSST-M. Only for perceived stress significant differences in SPS were observed, with more sensitive individuals perceiving more negative and less positive affect. For environmental quality and the interaction between SPS and Neuroticism results showed higher recovery rates of heart rate in high quality environments and stronger cortisol responses for adolescents scoring high on both SPS and Neuroticism. Potential explanations for these findings and implications for current theorizing on environmental sensitivity are discussed.

Improving the Measurement of Environmental Sensitivity in Children and Adolescents: The Highly Sensitive Child Scale-21 Item Version.

Children differ in their sensitivity to positive and negative environmental influences, which can be measured with the Highly Sensitive Child (HSC) scale. The present study introduces the HSC-21, an adaptation of the original 12 item scale with new items and factor structure that are meant to be more informative than the original ones. The psychometric properties of the HSC-21 were investigated in 1,088 children across Belgium and the Netherlands, including child and mother reports. Results showed evidence for (a) bifactor model with a general sensitivity factor and two specific factors (i.e., Ease of Excitation-Low Sensory Threshold and Aesthetic Sensitivity); (b) (partial) measurement invariance across gender, developmental stage, country, and informants; (c) moderate child-mother agreement; (d) good reliability; (e) normally distributed item scores; and (f) meaningful associations with personality and temperament across both samples. No evidence was found for HSC-21 as a moderator in the relationship between parenting and problem behaviors.

Epigenetics in Families: Covariance between Mother and Child Methylation Patterns.

Theory and research both point at epigenetic processes affecting both parenting behavior and child functioning. However, little is known about the convergence of mother and child's epigenetic patterns in families. Therefore, the current study investigated epigenetic covariance in mother-child dyads' methylation levels regarding four stress-regulation related genes (5HTT, NR3C1, FKBP5, and BDNF). Covariance was tested in a general population sample, consisting of early adolescents (Mage = 11.63, SDage = 2.3) and mothers (N = 160 dyads). Results showed that mother and offspring 5HTT and NR3C1 methylation patterns correlated. Furthermore, when averaged across genes, methylation levels strongly correlated. These findings partially supported that child and parent methylation levels covary. It might be important to consider this covariance to understand maladaptive parent-child relationships.

Spotting Loneliness at School: Associations between Self-Reports and Teacher and Peer Nominations.

In two independent studies, we aimed to examine the extent to which teacher and peer nominations of loneliness are associated with children's and adolescents' self-reported loneliness, respectively. Additionally, we examined whether loneliness nominations from teachers and peers were informative above and beyond peer status and social behaviors associated with loneliness. In Study 1 (N = 1594, Mage = 9.43 years), teacher nominations of loneliness showed a small to moderate correlation with children's self-reported loneliness as assessed using the Loneliness and Social Dissatisfaction Questionnaire (LSDQ). The results of a hierarchical regression analysis showed that teacher nominations of loneliness predicted children's self-reported loneliness above and beyond teacher nominations of peer status and social behaviors. In Study 2 (N = 350, Mage = 13.81 years), peer nominations of loneliness showed a small to moderate correlation with adolescents' self-reported loneliness as assessed using the peer-related loneliness subscale of the Loneliness and Aloneness Scale for Children and Adolescents (LACA). The results of a hierarchical regression analysis showed that peer nominations of loneliness predicted adolescents' self-reported loneliness above and beyond peer nominations of peer status and social behaviors. We conclude that loneliness nominations are valuable, but caution is needed when they are used exclusively to identify lonely children and adolescents.

Perspective taking, empathic concern, agreeableness, and parental support: Transactional associations across adolescence.

INTRODUCTION: Empathy consists of a cognitive and an affective component, of which it is thought that there are gender differences. Previous studies also suggest that maternal and paternal support play a more prominent role in the development of an adolescent's affective and cognitive empathy, respectively. Besides the environmental factor, that is parenting, adolescent personality, and more specifically, agreeableness, is closely linked to both empathy and support, but this interplay was not extensively investigated longitudinally. The present study investigated the transactional associations among parental support, adolescent agreeableness, and adolescent empathy. More specifically, we examined (a) whether maternal/paternal support is differentially associated with cognitive/affective empathy, while taking into account adolescent agreeableness and (b) whether adolescent agreeableness still predicts empathy, while taking into account parental support. METHODS: Data from 993 Belgian adolescents (MageT1 = 13.96 years; [12.6-18.4]) and their parents across four time points were used in a random intercept cross-lagged panel model. RESULTS: At the between-person level, maternal support was associated with affective, but not cognitive empathy, whereas agreeableness was associated with maternal and paternal support as well as with both types of empathy. At the within-person level, affective empathy predicted cognitive empathy one wave later. CONCLUSIONS: At a population level, agreeableness and support are both important in adolescent empathy development with limited evidence for the differential roles of mothers and fathers. Within participants, affective empathy, and not parental support or agreeableness, predicted cognitive empathy.

Loneliness, Social Anxiety Symptoms, and Depressive Symptoms in Adolescence: Longitudinal Distinctiveness and Correlated Change.

Loneliness, social anxiety symptoms, and depressive symptoms are internalizing problems that are highly intertwined and often co-occur during adolescence. This overlap and co-occurrence raises the question whether three different labels are used for the same underlying phenomenon. The present study adopts a comprehensive approach to this issue by investigating the development of the three phenomena simultaneously. Specifically, this study aimed to investigate (1) the developmental trend for all three internalizing problems separately, (2) whether they are best described by a single developmental trend, (3) how they co-develop across adolescence, and (4) gender differences in this co-development. The analyses were run in three three-wave longitudinal samples of adolescents with one-year intervals in order to verify the robustness of the findings. Sample 1 (roughly ages 15, 16, and 17) comprised 549 adolescents (63% girls), and Samples 2 and 3 (roughly ages 13, 14, and 15) comprised 811 adolescents (46% girls) and 1101 adolescents (52% girls), respectively. Latent growth curve modeling for the three phenomena separately showed either small increases or stable patterns. A comparison of a Multiple Indicator Latent Growth Model (MILGM) with a Parallel Process Latent Growth Curve Modeling (PPLGCM) showed that the three internalizing problems followed unique, but related, developmental trends across adolescence. The intercepts of the three phenomena were positively correlated with one another in all samples and increases in loneliness were associated consistently with increases in social anxiety symptoms. Only in Sample 3 evidence was found for a similar association between loneliness and depressive symptoms and between social anxiety symptoms and depressive symptoms. Except for differences in initial levels, gender differences in the development of the three problems were limited. Overall, the results of the present study clearly indicate that the three internalizing problems are longitudinally distinct from one another, but co-develop across adolescence.

Manifesto for new directions in developmental science.

Although developmental science has always been evolving, these times of fast-paced and profound social and scientific changes easily lead to disorienting fragmentation rather than coherent scientific advances. What directions should developmental science pursue to meaningfully address real-world problems that impact human development throughout the lifespan? What conceptual or policy shifts are needed to steer the field in these directions? The present manifesto is proposed by a group of scholars from various disciplines and perspectives within developmental science to spark conversations and action plans in response to these questions. After highlighting four critical content domains that merit concentrated and often urgent research efforts, two issues regarding "how" we do developmental science and "what for" are outlined. This manifesto concludes with five proposals, calling for integrative, inclusive, transdisciplinary, transparent, and actionable developmental science. Specific recommendations, prospects, pitfalls, and challenges to reach this goal are discussed.

Gene-environment interaction: New insights into perceived parenting and social anxiety among adolescents.

BACKGROUND: Social anxiety symptoms (SAS) are among the most common mental health problems during adolescence, and it has been shown that parenting influences the adolescent's level of social anxiety. In addition, it is now widely assumed that most mental health problems, including social anxiety, originate from a complex interplay between genes and environment. However, to date, gene-environment (G × E) interactions studies in the field of social anxiety remain limited. In this study, we have examined how 274 genes involved in different neurotransmission pathways interact with five aspects of perceived parenting as environmental exposure (i.e., support, proactive control, psychological control, punitive control, and harsh punitive control) to affect SAS during adolescence. METHODS: We have applied an analytical technique that allows studying genetic information at the gene level, by aggregating data from multiple single-nucleotide-polymorphisms within the same gene and by taking into account the linkage disequilibrium structure of the gene. All participants were part of the STRATEGIES cohort of 948 Flemish adolescents (mean age = 13.7), a population-based study on the development of problem behaviors in adolescence. Relevant genes were preselected based on prior findings and neurotransmitter-related functional protein networks. RESULTS: The results suggest that genes involved in glutamate (SLC1A1), glutathione neurotransmission (GSTZ1), and oxidative stress (CALCRL), in association with harsh punitive parenting, may contribute to social anxiety in adolescence. Isolated polymorphisms in these genes have been related to anxiety and related disorders in earlier work.Conclusions: Taken together, these findings provide new insights into possible biological pathways and environmental risk factors involved in the etiology of social anxiety symptoms' development. CONCLUSIONS: Taken together, these findings provide new insights into possible biological pathways and environmental risk factors involved in the etiology of social anxiety symptoms' development.

Repetitive Negative Thinking outperforms loneliness and lack of social connectedness as a predictor of prospective depressive symptoms in adolescents.

BACKGROUND: Repetitive Negative Thinking (RNT) is a well-established predictor in adolescents of emotional problems, such as depression. Surprisingly little research, however, has looked at the relative importance of RNT vs. more interpersonally relevant variables in the context of depression, such as loneliness and lack of social connectedness. OBJECTIVE: The present study, therefore, set out to examine whether RNT is a significant predictor when taking into account the contribution of loneliness and social connectedness. METHODS: A sample of 135 typically developing adolescents (N = 135; 79.3% girls; M age = 17.5; range 16-21) completed measures of depressive symptoms, RNT, loneliness and social connectedness at two time points with a 3-month interval. RESULTS: Results showed that above and beyond baseline depressive symptoms, RNT was the only other significant predictor of prospective depressive symptoms. CONCLUSIONS: According to these results, RNT seems a relatively more important factor to consider in the context of adolescent depression than factors in the interpersonal or social context. Consequently, targeting RNT might be expected to yield more significant gains in reducing or preventing depressive symptoms in adolescents compared to focusing on feelings of loneliness or social connectedness - a hypothesis that remains to be tested.

A SNP, Gene, and Polygenic Risk Score Approach of Oxytocin-Vasopressin Genes in Adolescents' Loneliness.

Not much is known regarding underlying biological pathways to adolescents' loneliness. Insight in underlying molecular mechanisms could inform intervention efforts aimed at reducing loneliness. Using latent growth curve modeling, baseline levels and development of loneliness were studied in two longitudinal adolescent samples. Genes (OXTR, OXT, AVPR1A, AVPR1B) were examined using SNP-based, gene-based, and polygenic risk score (PRS) approaches. In both samples, SNP- and gene-based tests showed involvement of the OXTR gene in development of loneliness, though, significance levels did not survive correction for multiple testing. The PRS approach provided no evidence for relations with loneliness. We recommend alternative phenotyping methods, including environmental factors, to consider epigenetic studies, and to examine possible endophenotypes in relation to adolescents' loneliness.

Transactional Links Between Social Anxiety Symptoms and Parenting Across Adolescence: Between- and Within-Person Associations.

This 4-year longitudinal multi-informant study examined between- and within-person associations between adolescent social anxiety symptoms and parenting (parental psychological control and autonomy support). A community sample of 819 adolescents (46.1% girls; Mage T1  = 13.4 years) reported annually on social anxiety symptoms and both adolescents and mothers reported on parenting. Between-person associations suggested that adolescent social anxiety symptoms were associated with higher adolescent- and mother-reported psychological control and lower mother-reported autonomy support. At the within-person level, however, mothers reported lower psychological control and higher autonomy support after periods with higher adolescent social anxiety symptoms. Our findings illustrate the importance of distinguishing among between-person and within-person associations and including perceptions of both dyad members in longitudinal research concerning parenting and adolescent mental health.

Investigating the interplay between parenting dimensions and styles, and the association with adolescent outcomes.

Research has indicated that a strictly dimensional or parental style approach does not capture the full complexity of parenting. To better understand this complexity, the current study combined these two approaches using a novel statistical technique, i.e., subspace K-means clustering. Four objectives were addressed. First, the study tried to identify meaningful groups of parents in longitudinal adolescent reports on parenting behaviour. Second, the dimensional structure of every cluster was inspected to uncover differences in parenting between and within clusters. Third, the parenting styles were compared on several adolescent characteristics. Fourth, to examine the impact of change in parenting style over time, we looked at the cluster membership over time. Longitudinal questionnaire data were collected at three annual waves, with 1,116 adolescents (mean age = 13.79 years) at wave 1. Based on five parenting dimensions (support and proactive, punitive, psychological and harsh control), subspace K-means clustering, analysed per wave separately, identified two clusters (authoritative and authoritarian parenting) in which parenting dimensions were interrelated differently. Authoritative parenting seemed to be beneficial for adolescent development (less externalising problem behaviour and higher self-concept). Longitudinal data revealed several parenting group trajectories which showed differential relations with adolescent outcomes. Change in membership from the authoritative cluster to the authoritarian cluster was associated with a decrease in self-concept and an increase in externalising problem behaviour, whereas changes from the authoritarian cluster to the authoritative cluster were associated with an increase in self-concept and a decrease in externalising problem behaviour.

Linking identity and depressive symptoms across adolescence: A multisample longitudinal study testing within-person effects.

This multisample longitudinal study examined the directionality of effects between identity exploration and commitment processes and depressive symptoms across adolescence. We compared two theoretical perspectives. According to the vulnerability model, identity uncertainty predicts depressive symptoms, whereas the scar model holds that depressive symptoms play into identity uncertainty. In investigating both models, we examined reciprocal within-person associations in Study 1 (N = 497, Mage Time 1 [T1] = 14.03 years, comprising five annual waves) and Study 2 (N = 1,022, Mage T1 = 15.80 years, comprising four annual waves). To this end, we applied the random-intercept cross-lagged panel model (RI-CLPM) in both studies. Results supported the vulnerability model across Studies 1 and 2. Specifically, within-person increasing reconsideration of commitment (Study 1) and ruminative exploration (Study 2) predicted a within-person increase in depressive symptoms 1 year later, but not vice versa. Commitment processes did not predict depressive symptoms at the within-person level. Our findings indicate that maladaptive exploration processes of identity formation play a particularly important role in the development of depressive symptoms at the within-person level. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Internalizing Problems in Adolescence: Linking Loneliness, Social Anxiety Symptoms, and Depressive Symptoms Over Time.

Adolescents are particularly vulnerable to experiencing loneliness, social anxiety symptoms, and depressive symptoms. These internalizing problems often co-occur but, until now, it remains unclear how they are associated over time. Insight in these temporal sequences is important to enhance our understanding of how internalizing problems arise and may reinforce each other over time. To examine these temporal sequences, three samples of adolescents were used: Sample 1 consisted of 1,116 adolescents (48.97% girls, Mage = 13.59), Sample 2 of 1,423 adolescents (52.42% girls, Mage = 13.79), and Sample 3 of 549 adolescents (62.66% girls, Mage = 14.82). Adolescents filled out well-established self-report measures of loneliness, social anxiety symptoms, and depressive symptoms during regular school hours at three measurement occasions with a 1-year interval. Meta-analytic techniques were used to estimate the average true effects across three-variable autoregressive cross-lagged models in the three samples. In addition, indirect effects and gender differences in the temporal associations were explored in all three samples. The results suggest that social anxiety symptoms play a crucial role as potential antecedent of emerging feelings of loneliness and depression in adolescence. In addition, in line with theoretical expectations, our results suggest the presence of a vicious cycle between adolescents' feelings of loneliness and social anxiety symptoms. The indirect effects were inconsistent across samples and no gender differences were found. These findings shed more light on the unique temporal relationships among different internalizing problems. Clinical interventions should target social anxiety symptoms to prevent feelings of loneliness and vice versa.

Loneliness and social anxiety across childhood and adolescence: Multilevel meta-analyses of cross-sectional and longitudinal associations.

Social relationships are of vital importance for children's and adolescents' development, and disruptions in these relationships can have serious implications. Such disruptions play a central role in both loneliness and social anxiety. Although both phenomena are closely related, they have largely been studied separately, and important questions have remained unanswered concerning how both go together within and across time. Multilevel meta-analyses were performed on 102 cross-sectional studies, published between 1981 and 2016, including 41,776 participants (39% males) with a mean age of 15.59 years. Longitudinal associations were examined in 10 studies, including 3,995 participants (46% males), using a novel technique that enables the examination of such associations even when these were not reported in the original empirical studies. Results indicated a strong, positive cross-sectional association between loneliness and social anxiety symptoms. This associations did not systematically differ in strength across childhood and adolescence. Moreover, results showed that loneliness and social anxiety symptoms were reciprocally associated over time. To conclude, loneliness and social anxiety symptoms are positively associated both within and across time, and across childhood and adolescence. Breaking this vicious cycle is of great importance, as both phenomena may be associated with profound problems in multiple domains of youth development. Moreover, failing to pay attention to both loneliness and social anxiety symptoms might substantially reduce the effectiveness of intervention programs focusing on either of the two. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Parenting Interacts with Oxytocin Polymorphisms to Predict Adolescent Social Anxiety Symptom Development: A Novel Polygenic Approach.

Guided by a developmental psychopathology framework, research has increasingly focused on the interplay of genetics and environment as a predictor of different forms of psychopathology, including social anxiety. In these efforts, the polygenic nature of complex phenotypes such as social anxiety is increasingly recognized, but studies applying polygenic approaches are still scarce. In this study, we applied Principal Covariates Regression as a novel approach to creating polygenic components for the oxytocin system, which has recently been put forward as particularly relevant to social anxiety. Participants were 978 adolescents (49.4% girls; Mage T1 = 13.8 years). Across 3 years, questionnaires were used to assess adolescent social anxiety symptoms and multi-informant reports of parental psychological control and autonomy support. All adolescents were genotyped for 223 oxytocin single nucleotide polymorphisms (SNPs) in 14 genes. Using Principal Covariates Regression, these SNPs could be reduced to five polygenic components. Four components reflected the underlying linkage disequilibrium and ancestry structure, whereas the fifth component, which consisted of small contributions of many SNPs across multiple genes, was strongly positively associated with adolescent social anxiety symptoms, pointing to an index of genetic risk. Moreover, significant interactions were found with this polygenic component and the environmental variables of interest. Specifically, adolescents who scored high on this polygenic component and experienced less adequate parenting (i.e., high psychological control or low autonomy support) showed the highest levels of social anxiety. Implications of these findings are discussed in the context of individual-by-environment models.