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Challenges to Health during Development

Dev Neurosci 2009;31:300–308 DOI: 10.1159/000216541

Individual Differences in Behavioral, Physiological, and Genetic Sensitivities to Contexts: Implications for Developmentand Adaptation

Jelena Obradović W. Thomas Boyce

Human Early Learning Partnership, University of British Columbia, Vancouver, B.C. , Canada

Individual Differences in Behavioral, Physiological,

and Genetic Sensitivities to Contexts: Implications

for Development and Adaptation

Decades of research have shown that exposure to en-vironmental adversity places children at high risk for cognitive, social, emotional, and health problems [1, 2] . Although it is well established that disorders of develop-ment and health are more prevalent among children from high-risk families [3, 4] , there is considerable variation in the adaptation of children exposed to both low and high levels of adversity [5, 6] . In recent years, researchers have made significant progress in understanding how social environments differentially shape children’s develop-ment. Studies indicate that not all children are equally susceptible to environmental effects. In this article, we review how individual differences at the behavioral, physiological, and genetic levels predispose children to be more or less susceptible to contextual influences that may affect adaptive functioning and health. Further, we re-view studies that bridge these three levels of analysis, not-ing associations among behavioral, physiological, and ge-netic indices of sensitivity to context. Finally, we propose that individual differences in such contextual sensitivity may be shaped by the quality of social environments to which children are exposed early in life and review recent work that supports this notion.

Key Words

Negative emotionality � Physiological reactivity � Gene-environment interactions

Abstract

Although exposure to adversity places children at high risk for developmental problems, there is considerable variation in the adaptation of children exposed to both low and high levels of adversity. In recent years, researchers have made significant progress in understanding how social environ-ments shape children’s development. Studies indicate that not all children are equally susceptible to environmental ef-fects. In this article, we review the studies that examine indi-viduals’ sensitivity to both positive and negative contextual influences at three levels of analysis: behavioral, physiologi-cal, and genetic. Furthermore, we examine how these differ-ent types of sensitivities may be related and whether early exposure to adversity plays an important role in shaping de-velopment of individual reactivity to contexts. We also sug-gest important directions for future studies of individual dif-ferences in susceptibility to environmental effects.

Copyright © 2009 S. Karger AG, Basel

Received: December 16, 2008 Accepted after revision: January 3, 2009 Published online: June 17, 2009

Jelena Obradović, PhD Human Early Learning Partnership, University of British Columbia 440-2206 East Mall Vancouver, B.C. V6T 1Z3 (Canada) Tel. +1 604 827 4068, Fax +1 604 822 0640, E-Mail jelena.obradovic@ubc.ca

© 2009 S. Karger AG, Basel0378–5866/09/0314–0300$26.00/0

Accessible online at:www.karger.com/dne

Sensitivity to Context Dev Neurosci 2009;31:300–308 301

Behavioral Sensitivity At a behavioral level of analysis, individual differences

in temperamental reactivity have been linked to higher levels of mental health problems in children. Negative emotionality, broadly defined, represents a tendency of certain children to respond to challenging, novel, or po-tentially threatening environmental stimuli with high levels of anger, frustration, discomfort, sadness, anxiety, and/or fear. Although Rothbart and Bates have argued that expressions of fear and anger should be examined separately as they are subserved by different brain cir-cuitries and show different developmental correlates [7] , most studies of children’s temperament employ indicesof negative emotionality that are not conceptually pure, sometimes even including measures of behavioral dys-regulation. Taking this conceptual and measurement ca-veat into account, negative emotional reactivity has been shown to predict higher levels of both internalizing and externalizing symptoms across childhood and adoles-cence [8–11] . Moreover, negative emotionality has been reported to uniquely predict the co-occurrence of exter-nalizing and internalizing symptoms [10] . In addition to associations with presyndromal psychopathology, nega-tive emotionality has been found to predict lower social competence [12] , lower attentional control [13] , and more consistent behavioral inhibition [14] .

Although behaviorally reactive children seem to be at higher risk for various developmental problems than their less reactive peers, this risk is moderated by the quality of environmental influences to which they are ex-posed. Studies have shown that behaviorally reactive in-fants may be more susceptible than less reactive peers to maternal care-giving behaviors. Maternal insensitivity and lack of warmth was found to be a stronger predictor of later distress, poor control, and ineffective self-regula-tion in infants and toddlers who showed high levels of negative emotionality, compared to infants with low lev-els of negative emotionality [15–17] . Furthermore, sev-eral studies have found that negative emotionality was associated with higher levels of externalizing behaviors only among children exposed to intrusive, negative, harsh or hostile parenting [9, 18–21] . Finally, Belsky [20] found that associations between child care quality and behavior problems were significant only for children high in nega-tive emotionality, suggesting that temperamentally reac-tive children may show higher susceptibility to adverse environmental influences. Thus, it appears that negative emotionality represents a risk for maladjustment espe-cially or solely in the context of high adversity.

Behaviorally reactive children may also be more sus-ceptible to positive contextual influences. Negative emo-tionality has been linked to greater behavioral and cogni-tive improvements in response to interventions [22, 23] . Moreover, children with negative emotionality showed higher levels of behavioral problems and lower social competence if exposed to low-quality childcare, butwhen exposed to high-quality childcare, they showed better adjustment than their low-reactive peers [24] .

Physiological Sensitivity At a physiological level of analysis, individual differ-

ences in autonomic stress reactivity have been associated with various developmental problems. In general, two different profiles of autonomic reactivity emerge. Under-arousal during the resting state or in response to chal-lenging stimuli tends to be related to externalizing symp-toms, while overarousal is associated with internalizing symptoms. This pattern of findings has been found across various indices of sympathetic and parasympathetic ner-vous system reactivity, and is briefly reviewed here. For a more detailed description of various stress reactivity in-dices and a more extensive overview of the current litera-ture, consult [25] .

Diminished skin-conductance level (SCL) reactivity, an index of peripheral sympathetic nervous system (SNS) activity, has been associated with a variety of externa l-izing problems in children and adolescents [26–28] .Both low basal SCL and low SCL reactivity to negatively charged stimuli have been associated with conduct prob-lems in children [29] and with attention-deficit/hyperac-tivity disorder in preschoolers and adolescents [28, 30] . In contrast, high SCL reactivity to stressful or challeng-ing stimuli has been linked to higher levels of internal-izing problems in children, including behavioral inhibi-tion [31] , anxiety [32] , and fearfulness [33] . Although studied to a lesser extent, individual differences in car-diac pre-ejection period (PEP), the only noninvasive car-diac measure of pure SNS activation, have also been linked to developmental psychopathology. Lower PEP re-activity in response to a series of challenges was observed in children with high levels of externalizing symptoms in comparison to children with low levels of behavioral symptoms [34] . Furthermore, children with clinical lev-els of externalizing symptoms showed both a longer base-line PEP and lower PEP reactivity in response to reward, indicating hyporesponsivity of the SNS and reward in-sensitivity [28, 35] .

Respiratory sinus arrhythmia (RSA), a measure of parasympathetic nervous system (PNS) response indexed

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by heart period variability within the frequency range as-sociated with the respiratory cycle, has been conceptual-ized as an index of children’s regulatory abilities in re-sponding to positive and negative environmental de-mands [35, 36–39] . RSA reflects the efferent projections of the vagal nerve, which in situations of rest and calm suppresses sympathetic tone to the heart and produces the baseline heart rate. In stressful or challenging situa-tions, on the other hand, vagal efferent signal withdraw-al removes sympathetic suppression, allowing the SNS to generate a faster heart rate [38–40] . Low basal levels of RSA may reflect emotional lability and dysregulation and have been linked to behavior problems in at-risk and clin-ical samples across childhood and adolescence [35, 36, 41–44] . Moreover, low RSA reactivity in response to labo-ratory challenge has been associated with externalizing symptoms in normative, nonclinical samples of young children [34, 45] .

On the other hand, high RSA reactivity (i.e. greater vagal withdrawal) during challenging tasks has been as-sociated with more sustained attention, better emotion regulation, and increased engagement [46, 47] . In com-munity samples of kindergarten children, higher RSA re-activity has been associated with some positive indices of adaptation, such as sociability, attention, and capacity for work [48, 49] . However, high RSA reactivity has been also linked to high levels of internalizing symptoms and co-occurring internalizing and externalizing behavioral problems [34, 45, 50, 51] . In addition, high RSA reactivity has been observed in children with clinical levels of be-havior problems [35, 52] . Thus, while low PNS reactivity is associated with poor regulatory capacities, emotional lability, and risk for externalizing problems, high PNS reactivity is associated with both positive and negative indices of adaptation, underscoring the need for research-ers to go beyond simple linear tests of associations be-tween psychophysiology and behavior and also consider sample characteristics.

Although the current literature indicates that indi-vidual differences in ANS reactivity to stress represent important correlates of health and adaptation in chil-dren and adolescents, recent studies emphasize the need to examine interactions between reactivity and environ-mental influences. Children who respond to challenging laboratory tasks with heightened stress responses across different ANS indices tend to be more susceptible to con-textual factors in their lives. As such, highly reactive children may show poor adaptation and health in con-texts of high adversity exposure, but may show success-ful adaptation and good health in supportive and nur-

turing contexts. Indeed, both sympathetic and parasym-pathetic reactivity have been associated with lower competence and lower mental and physical health in the context of high adversity, but higher competence and health in the context of low adversity. For example, high SCL reactivity to emotional and cognitive tasks was as-sociated with high or increasing levels of internalizing symptoms, externalizing symptoms, and social and cog-nitive problems, but only in children who were exposed to high levels of paternal depression [53] or marital con-flict [54, 55] . Similarly, a recent study of kindergartners demonstrated that high RSA reactivity was associated with higher levels of externalizing problems and lower levels of prosocial behavior, school engagement, and ac-ademic competence in the context of high family adver-sity. Equally high RSA reactivity was associated, on the other hand, with better adaptation and lower symptoms in the context of low family adversity [56] . Further, in a clinical sample, parental psychopathology had a nega-tive effect on children’s emotional and behavioral prob-lems only in children with high baseline RSA [57] . Fi-nally, Boyce et al. [58] examined whether an aggregate measure of SNS and PNS reactivity, mean arterial pres-sure (MAP), was a risk factor for short-term physical health problems in children. Interactions between MAP reactivity and exposure to environmental stressors pre-dicted the incidence of respiratory illnesses, such that highly reactive children had the highest incidence of ill-nesses in the context of high stress and the lowest inci-dence of illnesses in the context of low stress.

It is important to note, as well, that several studies have shown that high RSA reactivity may protect children against the deleterious effects of emotional negativity within family interactions. For example, high basal RSA levels and high RSA reactivity in response to emotional stimuli buffered children from the negative effects of marital conflict and hostile-withdrawn parenting on ac-ademic achievement, peer competence, and physical and mental health [59–64] . Thus, more research is needed to examine the specific implications of different physiolog-ical responses for developmental outcomes under varied environmental circumstances. Moreover, researchers must examine how the nature of stimuli used to elicit ANS response affects the relation between reactivity and adaptation across different levels of exposure to adversity. Children who confront certain types of adversities may react differently to laboratory stressors that embody the types of adversity salient in their lives than to stressors that are less personal [65] .

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Genetic Sensitivity In recent years researchers have begun to identify

functional genetic polymorphisms that are associated with various indices of adaptive functioning or that are more prevalent among children with developmental problems. A full review of allelic variations that put groups of children at risk for developmental problems is beyond the scope of this paper. However, nascent research indicates that, as with behavioral and physiological reac-tivity, allelic variation within certain genes moderates the effects of environmental adversity on children’s adapta-tion and health. We describe only a few exemplary studies of gene-environment interactions; for a more detailed re-view, see Rutter et al. [66] . The longitudinal birth cohort study in Dunedin, New Zealand represents landmark work on how genes and contexts interactively influence behavior. In a pioneering paper, Caspi et al. [67] found that individuals who experienced maltreatment in child-hood were more likely to develop antisocial behavior in adulthood if they possessed an allele coding for low levels of the enzyme metabolizing the neurotransmitters sero-tonin, epinephrine and norepinephrine (monoamine ox-idase A, MAOA) than if they possessed an allele that cod-ed for high levels.

In another paper utilizing data from the Dunedin study, Caspi et al. [68] reported that individuals with one or two copies of the short allele in the promoter region of the serotonin transporter gene (5-HTTLPR, the sero-tonin-transporter-linked polymorphic region) were at greater risk for development of depressive problems when exposed to high levels of stressful life events. In a sample of maltreated children, Kaufman et al. [69] corroborated these findings by showing that children who had both the short allele of the 5-HTTLPR gene and low social support had higher levels of depression symptoms than all other groups of children. Genetic sensitivity associated with an allelic variation in the serotonin transporter gene has also been found in nonhuman primates [70] . Rhesus ma-caques with a short allele of the 5-HTTLPR gene were especially vulnerable to increased alcohol consumption when raised in more stressful peer-only rearing condi-tions, as compared to macaques raised by mothers. Yet another example of genetic sensitivity to environmental influences has been found in the dopamine receptor gene (DRD4) 7-repeat polymorphism, which has been associ-ated with disorganized attachment classification in in-fants [71] and externalizing symptoms in children [72] . Van Ijzendoorn and Bakermans-Kranenburg [73] found that infants with the 7-repeat allele who were exposed to their mothers’ unresolved loss and trauma were many

times more likely to be classified as having disorganized attachment than infants without the allele. Bakermans-Kranenburg and Van Ijzendoorn [74] have also shown that children with the 7-repeat allele who were exposed to insensitive care were more likely to develop external-izing behavior problems than other groups of children. Most importantly, children who had the 7-repeat allele and whose parents showed an increase in positive disci-pline as a result of parenting intervention showed the largest decreases in externalizing symptoms [75] .

Integrating Multiple Levels of Analyses As expanding empirical evidence converges on the ob-

servation that not all children are equally susceptible to either negative or positive environmental effects, re-searchers have theorized that reactivity, whether mea-sured at the behavioral or biological level, is not a unitary, pathogenic response to adversity that invariably leads to maladaptation. Boyce and colleagues have challenged the traditional view of stress reactivity as a risk factor for physical and mental morbidities, arguing that reactivity is better conceptualized as a high biological sensitivity to both positive and negative contexts [4, 76] . They argue that the effects of high biological sensitivity may be mal-adaptive in the context of adversity but positive in re-sponse to nurturing and supportive environments [77] . Likewise, Belsky and colleagues have posited that tem-peramentally vulnerable children may show higher sus-ceptibility to environmental influences that may lead to better or worse adaptive outcomes depending on the quality of contextual factors [20, 78] . Finally, recent re-search demonstrating the multiplicative effects of genet-ic polymorphisms and contextual factors [67, 73, 79, 80] suggests that this differential susceptibility to environ-mental influences can be studied at multiple levels of analyses. Future studies are needed to determine wheth-er these behavioral, physiological, and genetic markers of sensitivity to contextual factors constitute the same phe-nomena expressed at different levels of assessment or rep-resent different types of susceptibility that may have cu-mulative or multiplicative effects on development.

Currently available evidence suggests significant as-sociations between measures of negative emotionality and physiological indices of stress reactivity. Most studies examining links between behavioral and biological reac-tivity have focused on expressions of fear and anxiety(i.e. behavioral inhibition), emotions that fall under the broad conceptualization of negative emotionality but have a different biological basis than expressions of frus-tration, irritability, and a lack of soothability [7] . Higher

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heart rate and lower resting RSA have been observed in temperamentally fearful children when compared to less-fearful age mates [81] . Moreover, some researchers have argued that SCL reactivity reflects individual differences in behavioral inhibition and the passive avoidance ten-dencies associated with fear and anxiety. SCL reactivity has been found to increase under the threat of punish-ment but to be unaffected by reward [33, 36, 57] . Finally, fearful temperament, as indexed by freezing behavior in the presence of a stranger, has been associated with short-er resting PEP in toddlers [82] .

In a recent study, Buss et al. [83] examined associa-tions in observer-rated indices of negative affect (e.g. fa-cial distress, crying, escape) and indices of ANS reactiv-ity (i.e. HR, RSA, and PEP) in toddlers during cognitive and fear- and anger-inducing challenges. Expressions of negative affect were positively related to concurrent heart rate during emotion-evocative challenges. Moreover, in girls, changes in HR from baseline levels in response to cognitive and emotional challenges were related to chang-es in negative affectivity. This study highlights the im-portance of examining whether associations between be-havioral and biological reactivity vary systematically by gender. In addition, researchers should employ a develop-mental framework, as these associations may change with the maturation of systems subserving reactive pro-clivities. For example, higher levels of basal RSA in in-fancy have been linked to temperamental difficulty and emotional negativity [84, 85] , whereas high levels of bas-al RSA later in toddlerhood and childhood have been as-sociated with higher social competence, empathy, emo-tion regulation, and lower aggression [36, 48, 50, 86–88] .

Although significant associations between behavioral and physiological reactivity have been noted, the magni-tude of these associations is relatively low, and these stud-ies are far from corroborating the notion that behavioral and physiological reactivity represent the same phenom-ena. Moreover, some studies have reported no significant association between ANS reactivity and concurrent ex-pression of distress [89] or behavioral inhibition [90] . There is, at present, a paucity of studies examining asso-ciations between behavioral and physiological reactivity across different socioeconomic contexts and levels of ad-versity exposure. This is an important new direction for research, as the coupling of two types of reactivity may vary across different contexts. A few recent studies have shown that the quality of the parent-child relationship moderated the effect of temperament on SCL reactivity to fear-inducing films, such that fearful children with

low-quality parenting showed high reactivity, while fear-ful children with high-quality parenting showed low re-activity [91, 92] .

Finally, a few recent studies have examined associa-tions between genetic polymorphisms and behavioral and physiological reactivity. Studies of a functional poly-morphism in the promoter region of the serotonin trans-porter gene (5-HTTLPR) have revealed mixed associa-tions with behavioral inhibition, fearfulness, and shyness in children [72, 93] . However, interactions between al-lelic variation within the 5-HTTLPR gene and environ-mental influences have been found to predict behavioral inhibition in children and nonhuman primates [94, 95] . The short allele of the 5-HTTLPR gene, associated with diminished gene transcription and lower serotonin reup-take, has been linked to higher levels of behavioral inhi-bition among children whose mothers reported low levels of social support [95] . Lastly, Derijk et al. [96] have dem-onstrated associations among polymorphisms in the genes coding for mineralocorticoid receptors (MR) and HR reactivity in response to a laboratory psychosocial challenge.

Overall, more research is needed to examine how dif-ferent indices of sensitivity to contexts relate within dif-ferent groups of children and across varied contexts. In addition to hierarchical integration of indices across mul-tiple levels of analysis, researchers should strive to gain a deeper understanding of how different indices of behav-ioral, biological, and genetic sensitivity interact at the same level of analysis. Infants high in negative emotion-ality and motoric reactivity are more likely to consistent-ly exhibit behavioral inhibition across the first 4 years of life [14] . However, Belsky et al. [19] revealed that infants high in negative emotionality were less behaviorally in-hibited toddlers if they were exposed to harsh fathering, whereas behavioral inhibition of infants low in negative emotionality was unaffected by fathering quality. More-over, associations between negative emotionality and adaptive functioning have been shown to depend on the regulatory dimension of temperament, such that negative emotionality represents a risk factor only for children who also show low levels of self-regulation [97] . Similarly, studying the interplay among different aspects of the physiological stress response may reveal a more nuanced understanding of susceptibilities to context than study-ing one system at a time. Boyce et al. [34] examined how different ANS stress reactivity profiles – as indexed by PNS and SNS reactivity to various laboratory challeng-es – related to behavior problems. Stress reactivity pro-files differentiated four groups of children who showed

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either high internalizing symptoms, high externalizing symptoms, high co-occurring internalizing and exter-nalizing symptoms, or low symptoms. In comparison with the low symptom group, internalizers were char-acterized by heightened PNS reactivity, externalizers showed diminished PNS and SNS reactivity, and chil-dren with comorbid symptoms exhibited only lower SNS reactivity.

The Importance of Early Experience Individual differences in behaviorally, physiologically

and genetically indexed sensitivities to social contexts may predispose certain children to positive and negative environmental influences, but the quality of environ-ment may also play a reverse role in shaping the develop-ment of children’s contextual sensitivity. Boyce and col-leagues [4, 76] have proposed, in an evolutionary argu-ment, that the quality of early experience may influence children’s biological sensitivity to context. Children raised in stimulating and nurturing contexts may dispro-portionately develop high biological sensitivity in order to take maximal advantage of positive environmental in-fluences. Children growing up in harsh and threatening environments might also develop high biological sensi-tivity as a means of maintaining the high levels of vigi-lance required for survival. In contrast, the majority of children, raised in environments that fall within neither of these two extremes, may develop lower biological sen-sitivity, as the environments to which they are exposed are neither highly nurturant nor highly threatening. Boyce and colleagues thus suggest that the relation be-tween early experience and biological sensitivity maybe curvilinear or U-shaped, with high-reactivity pheno-types most prevalent in the contexts of low and high adversity exposure [4, 76] .

Some recent empirical work supports the idea that early experience may ‘program’ an individual’s sensitiv-ity to later contextual influences. Studies of stress reactiv-ity in preterm infants indicate that neonatal exposure to pain affects biological and behavioral reactivity to pain and novelty [98–100] . Grunau et al. [100] suggest that there is a re-setting of the endocrine stress response sys-tem across the first year of life, as there is a shift in asso-ciation between pain-stress and basal cortisol levels in infants born at extremely low gestational age. The qual-ity of early parent-child relationships may also play an important role in shaping children’s responses to stress and adversity. Infants classified as having insecure-avoid-ant attachment have been found to show higher PNS re-activity during the Strange Situation paradigm and high-

er overall SNS responses [101] . In contrast, Burgess et al. [102] found that an avoidant attachment classification in infancy was unrelated to concurrent ANS reactivity, but it predicted underarousal, as indexed by lower HR and high levels of RSA, when children were four years old. Although insecure attachment can serve as a proxy of early exposure to insensitive care-giving, it may not ac-curately represent the level of adversity exposure. How-ever, a recent study of traumatized 1.5- to 6-year-olds who had experienced a life-threatening event or wit-nessed an event that threatened the life of an immediate relative revealed that the interaction between the severity of children’s PTSD symptoms and the observed quality of parental discipline predicted children’s ANS reactivity [103] . Children who had high levels of PTSD symptoms and were exposed to low levels of positive discipline showed the highest PNS reactivity in response to recall-ing a traumatic personal event.

Finally, it is important to consider how the modifica-tions of stress-responsive gene expression, via epigenetic modifications of chromatin structure, DNA methylation, and histone acetylation, may contribute to individual dif-ferences in reactivity. Experience-based alterations in the chromatin packaging of DNA may calibrate the tran-scription of genes involved, either peripherally or cen-trally, in the development and regulation of stress reac-tivity. Rokutan and colleagues, for example, studied 1,467 genes in peripheral blood leukocytes before and after a 6-hour examination of Japanese doctoral students [104, 105] . Their comparisons yielded 49 upregulated genes and 21 downregulated genes, most of which coded for cytokines, cytokine receptors, growth- or apoptosis-re-lated molecules, and heat-shock proteins. These findings suggest that stressful events can trigger acute responses in leukocytes that are mediated by changes in gene ex-pression. McGowan et al. [106] have summarized evi-dence that naturally occurring variation in both mater-nal behavior and diet in rats can effect changes in off-spring stress reactivity through glucocorticoid receptor gene expression. These regulatory influences are associ-ated with altered histone acetylation, DNA methylation, and nerve growth factor-inducible protein A (NGFI-A) transcription factor binding. Further, in a study of hu-man infants, Oberlander et al. [107] have presented data indicating that fetal exposure to third-trimester mater-nal depression is related to increased methylation of the glucocorticoid receptor gene (NR3C1) at an NGFI-A binding site and exaggerated salivary cortisol responses to a stressor at 3 months of age. Taken together, these hu-man and animal studies offer promising new insights

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into epigenetic processes by which early environmental exposures and the expression of stress-responsive genes may shape the individual’s sensitivity to environmental influences.

Conclusion

This review highlights the importance of studying in-dividual differences in children’s sensitivity to context at the behavioral, physiological, and genetic levels in order

to gain a more comprehensive understanding of how dif-ferent social contexts may shape children’s adaptation and health. Many studies demonstrate that certain chil-dren may be particularly susceptible to both positive and negative environmental influences, and nascent research indicates that the quality of early experiences may shape development of such reactivity. Future studies should employ developmental frameworks and longitudinal study designs in order to identify processes contributing to development of reactivity phenotypes and their influ-ences on development across multiple social contexts.

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