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Part IV

Applications to Development

Handbook of Developmental Science, Behavior, and GeneticsEdited by Kathryn E. Hood, Carolyn Tucker Halpern, Gary Greenberg, and Richard M. Lerner© 2010 Blackwell Publishing Ltd. ISBN: 978-1-405-18782-4

17

Gene-Parenting Interplay in theDevelopment of Infant Emotionality

Cathi B. Propper, Ginger A. Moore,and W. Roger Mills-Koonce

Why do some infants become happy, even-tempered, and agreeable children,whereas others become irritable, anxious, or emotionally intense and labile? Thesequalities of emotionality are often apparent in early infancy and reflect processesthat are integral components of temperament (e.g., Buss & Plomin, 1984;Goldsmith & Campos, 1982; Rothbart & Derryberry, 1981). Temperament isgenerally thought to be a set of inherited personality traits that are observable andstable from early infancy onward (Buss & Plomin, 1984; Rothbart, Ahadi, &Evans, 2000). Despite the emphasis on the genetic underpinnings of temperamentand its stability across the lifespan, theory and empirical research suggest that corecomponents of temperament, particularly emotionality, can be substantiallymodified by early environmental experiences (e.g., Kagan, 1989).

The origins of infant emotion reactivity and regulation, fundamental compo-nents of temperament, have been studied from various perspectives over the pastseveral decades. Emotion reactivity is defined as an individual’s response to astimulus change, or an alteration in the environment, which is reflected in changesin the somatic, endocrine, and autonomic nervous systems. This change isobserved in the excitability or arousability of response systems in both temporalfeatures (e.g., how fast responses begin after stimuli, how rapidly they escalate,how long they last, how slowly they go away) and intensity features (e.g., howstrongly responses are expressed, how sensitive they are to stimulation). Emotionregulation has been defined as “extrinsic and intrinsic processes responsible formonitoring, evaluating, and modifying emotional reactions, especially their in-tensive and temporal features, to accomplish one’s goals” (Thompson, 1994,p. 27–28).

Handbook of Developmental Science, Behavior, and GeneticsEdited by Kathryn E. Hood, Carolyn Tucker Halpern, Gary Greenberg, and Richard M. Lerner© 2010 Blackwell Publishing Ltd. ISBN: 978-1-405-18782-4

Developmental theories focus on experiences within families, especiallyparenting, as the primary influence on child development. During the first yearsof life, parent--infant relationships may have an impact on the developmentof emotionality by altering biological processes that are involved withfundamental component processes of reactivity and regulation, including geneticactivity (e.g., Caspi et al., 2003), physiological or hormonal responses (e.g., Gunnar& Donzella, 2002), and neural networking (e.g., Schore, 2000). Various theoreticalperspectives propose that sensitive and responsive parenting may facilitate theorganization of infants’ physiological systems needed to support optimal emotionreactivity and effective emotion regulation (Panksepp, 1986; Schore, 2000;Siegel, 2001).

Despite the primacy of parenting in developmental theories, causality cannotbe attributed to one factor as the origin of a given developmental outcome. Instead,as Gottlieb proposed in his theoretical expositions of a developmental systemsmodel, it is the coaction among environmental, behavioral, neural, and geneticlevels over time that pushes development forward (Gottlieb, 1991, 1998; Gottlieb&Halpern, 2002). The bidirectional movement of traffic within and among severallevels of analyses results in probabilistic epigenesis, that is, outcomes that areprobabilistic, rather than pre-determined (Gottlieb, 1970). Consequently, organ-isms with a similar genetic makeup may sustain very different outcomes based oncoactions with diverse life experience (Caspi et al., 2002; Heim et al., 2000).

Chapter Structure

In this chapter,we useGottlieb’s developmental systemsmodel to frame discussionof coactions between genetic mechanisms and parenting as contributors todevelopment of infants’ temperament, specifically via endophenotypic develop-ment of physiological processes that are related to emotion reactivity and regula-tion. We propose that the coaction of parenting and genetic processes affects theexpression of infants’ temperament through their impact on rapidly developingphysiological systems of emotion reactivity and emotion regulation. The impact ofparenting during developmentally sensitive periods, such as early infancy, mayhave an important adaptive function, affording a plasticity that prepares individualsto adaptmost successfully to the environment intowhich they are born (e.g., Boyce& Ellis, 2005).

Consistent with Gottlieb’s delineation of the limited utility of broadmeasures ofheritability for developmental analysis and the proposal of Moffitt, Caspi, andRutter (2006, p. 9) that the search for gene-environment mechanisms should betheoretically driven beginning with “plausible triads” (i.e., gene, environmentalfactor, behavioral phenotype), in this chapter we focus on literature that hasexamined specific candidate genes, on parenting as an environmental factor, and on

530 Propper, Moore, and Mills-Koonce

stability and change in infants’ emotionality, indexed by physiological and beha-vioral functioning, as phenotype.

First we briefly define the mechanisms of gene-environment correlation (rGE)and gene-environment interaction (G�E), where E is defined here as parenting,and discuss how these mechanisms may affect the development of infants’emotionality. A consideration of gene-environment correlation is necessary inanalyses of gene-environment interactions. Next we describe genetic literaturerelated to dopamine and serotonin, and interactions between relevant candidategenes and parenting in relation to elements of temperament. We then provide anexplanation of physiological processes associated with emotional regulation, as anelement of temperament, and describe literature linking these processeswith infantbehavior and development.We also describe how these processesmaymediate thecoactional contributions of parenting and genetic expression to infant emotionaldevelopment. We conclude with a discussion of implications for future research.

Gene-Environment Correlation

Gene-Environment Correlation and Stability In Infants’ Emotionality

Genetic contributions to a child’s emotionality may be related to measures ofparenting because of rGE. Although three types of rGE are defined: passive, active,and evocative (e.g., Scarr & McCartney, 1983), evocative rGE, described below, ismost relevant to the current discussion of coactions between children’s geneticmakeup and parenting. Passive rGE occurs when genes shared between the childand parent contribute to both infant emotionality and parenting. Active rGE occurswhen genetic characteristics of the child contribute to his or her active choice ofenvironmental experiences. Because the genetics of parenting are beyond the focusof this chapter (see Ganiban, Leve, Moore, & Neiderhiser, 2008 for a recentdiscussion of this topic) and because infants are not able to make active choicesabout the parenting environments intowhich they are born, passive and active rGEwill not be considered further in this chapter.

Evocative rGE occurs when genetically influenced characteristics of the child,such as emotionality, elicit specific responses from the parent. For example, a childwho shows a high level of negative reactivity to events and is difficult to soothemayhave a parent who becomes overwhelmed or frustrated and, in response, is morenegative or intrusive and therefore less sensitive. Passive and evocative rGEmay bedifficult to disentangle. For example, a child whose parent has a geneticallyinfluenced tendency towards negative emotionality that affects his or her parent-ing, may inherit those genetic factors, increasing the likelihood of displayingbehaviors that elicit negative, insensitive parenting. In this case, parenting does notnecessarily have a causal influence on the expression of child emotionality. Rather,

Gene-Parenting Interplay in Infant Emotionality 531

the twomay be associated because of genetic influences shared between parent andchild, or because of evocative rGE.

Research provides evidence for evocative rGE. O’Connor, Neiderhiser, Reiss,Hetherington, & Plomin (1998) found that children born to mothers with higherrates of antisocial behaviors, who are more likely than other children to inheritnegative emotionality, were more likely to receive negative parenting from theiradoptive caregivers, and that this associationwasmediated by children’s disruptivebehaviors. Ge, Conger, Cadoret, & Neiderhiser (1996), also using an adoptiondesign, found comparable results, whereas Riggins-Caspers, Cadoret, Knutson, &Langebehn (2003) found that such evocative child effects were primarily found inadoptive families with high cumulative social risk (e.g., alcohol abuse, depression,divorce). Although adoption studies have been fruitful in identifying children’sgenetic variability as a potential source of variation in parenting behaviors, theability to examine directly candidate genes and their contributions to the familysystem is a relatively new approach to examining coactions among genes andenvironments (Rutter, Moffitt, & Caspi, 2006).

Molecular genetics research has made many advances in recent developmentaland family studies. Research by Propper, Willoughby, Halpern, Carbone, &Cox (2007), Propper et al. (2008) and Mills-Koonce et al. (2007) suggest thatchildren with specific polymorphic variations in two dopamine receptor genes(DRD2 and DRD4) that are associated with behaviors indicative of problematicemotion reactivity and regulation (e.g., novelty seeking, impulsivity; see Clonin-ger, 1987; Ebstein et al., 1998; Noble et al., 1998; Suhara et al., 2001) receive lowerlevels of sensitive caregiving from their mothers. Mills-Koonce et al. (2007) foundthat this association was not due to maternal variations in the DRD2 polymorph-ism, suggesting that thismaybe an evocative rather than passive gene-environmentcorrelation.

Regardless of whether any given correlation between child genotype andparental behavior is passive or evocative in nature, an appreciation of gene-environment correlations within a research sample may be critical for under-standing the implications (and potential limitations) of specific interactions be-tween genes and environment. Furthermore, these associations highlight theimportance of differentiating the statistical term, interaction, from the epigeneticterm, coaction. In this light, it is important to remember that child genotype andparental phenotypic behavior are both part of one family (Cox & Paley, 2003) andone developmental epigenetic (Gottlieb, 1998) system, and that the co-dependen-cies between these separate genetic and behavioral subsystemsmust be consideredwith respect to how they jointly organize the function and activities of eachmember of the family system (Cairns, 1997).

Nevertheless, to the extent that infant emotionality is influenced by geneticfactors, in most cases we would expect mechanisms of rGE to increase stability ofemotionality over time. Examining mechanisms of gene-environment interaction(G�E) may provide a clearer understanding of change in emotionality and how


parenting could modify aspects of infant emotionality that are initially geneticallyinfluenced.

Gene-Environment Interaction and Change in Infant Emotionality

Gene-environment interaction occurs when individuals with different genotypeshave differential responses to the same environmental factor. For example, theimpact of harsh, negative parenting may be greater (or lesser) on a child with agenetic risk for negative emotionality. Here it is important to note that processes ofrGE and G�E can occur simultaneously. Passive rGE and evocative rGE, asdescribed above, andG�Emay all be operating in the following example: A parentand child have a shared genetic tendency toward negative emotionality (passiverGE), the parents’ negative emotionality is elicited frequently by the child’snegative emotionality (evocative rGE), and the child’s genotype may make himdifferentially sensitive to the harmful effects of harsh, negative parenting (G�E).Again, however, we would expect these processes working in tandem to result insubstantial stability in infants’ emotionality. Thus, in a context where rGE isexpected, that is, biological parents rearing their children, developmental theoriesshould take into account that parentingmaynot have a consistently strong effect onchange in a child’s emotionality.

One of the lessons ofmuch of the behavioral genetics research of the past decadeis that for children who do not carry specific risk genotypes, some presumablynegative environmental experiences, such as harsh, negative parenting, may havelittle, or variable, effects on aspects of their functioning. For example, recentresearch found that infants who did not carry a specific form of the dopaminereceptor gene DRD2 (taq1 A1) that has been associated with negative outcomesshowed effective physiological regulation of emotion (measured as change in vagaltone in response to maternal separation) regardless of parenting sensitivity. Infantswho did carry the taq1 A1allele showed ineffective physiological regulation at 3 and6 months, again regardless of parenting sensitivity, but, by 12 months, showedeffective physiological regulation if their mothers were rated as being higher insensitivity (Propper et al., 2008; see Figure 17.1). This example of G�E illustrates adifferential sensitivity to parenting as a function of genotype.

TheG�E interaction described above unfolds over time. At 3 and 6months, thepresence of the taq1 A1 DRD2 allele was associated with atypical lack of vagalwithdrawal in a challenging situation, suggesting less effective physiologicalregulation. This pattern represents a fixed strategies pattern (Belsky, 2005) witha main effect for genotype. By 12 months, the statistical interaction betweengenotype and parenting was evident, such that only infants at dual risk, geneticallyand environmentally, showed the atypical lack of vagal withdrawal. This unfoldingof an interaction between genotype and parenting over time illustrates the conceptof coactions between genes and environment.


Differential Susceptibility Hypothesis

In a variation of G�E theory, the differential susceptibility hypothesis (e.g.,Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007), individuals with aspecific genotype are proposed to be more susceptible than other children toenvironmental influences, whether those influences act as risk or protectivefactors. This formulation of G�E proposes that specific genotypes may makesome children show enhanced negative effects when interacting with environ-mental risk factors, but also show enhanced positive effects when interacting withenvironmental protective factors.

Assume, hypothetically, in the research previously discussed, that infants withthe taq1 A1 DRD2 allele that appears to confer risk for ineffective physiologicalregulation, showed a differential susceptibility to parenting. In this case, infants inthe risk genotype group with mothers rated low in sensitivity would showsignificantly lower values of the expected physiological response than all otherinfants, regardless of genotype, whereas infants in the risk genotype group withhighly sensitive mothers would show significantly higher values of theexpected physiological response than all other infants, including those withoutthe “risk” allele. This pattern of results would support the differential susceptibilityhypothesis, providing evidence that infants with a particular genotype showedincreased negative effects when exposed to an environmental risk factor (insensi-tive parenting) and increased positive effects when exposed to an environmentalprotective factor (sensitive parenting). In this hypothetical example, as in theactual research, the physiological regulation of children without the risk genotypeis not affected by parenting, although that is not a condition of the differentialsusceptibility model.

RSA Reactivity at 12 months

–1 SD Average + 1 SD

Maternal sensitivity

Non-Risk genotypeRisk genotype

B = –.24, n.s.

B = .36, p = .02

–0.4

–0.3

–0.2

–0.1

0

0.1

0.2

0.3

0.4

0.5

0.6

Figure 17.1. Gene-parenting interaction effect: Amount of infants’ RSA reactivity in achallenge task as a function of maternal sensitivity.


The differential susceptibility model differs from the traditional G�E sensitivitymodel in that it does not assume that a particular genotype confers a susceptibility toenvironmental influences in only one direction (i.e., either risk or protective), butthat a particular genotypemay confer a heightened susceptibility to bothpositive andnegative rearing influences (Belsky et al., 2007). Furthermore, the model suggeststhat specific genes may have been selected over time because of the differentialadvantage they confer in favorable environments. Of note, this model emphasizesthat a more appropriate way of conceptualizing risk or protective factors is in termsof coactions between genes and environment over time rather than conceptualizingeither genes or environments as risk or protective factors in and of themselves.

We propose that genetic contributions to emotionality can bemodified by earlyexperience in parent-child relationships and that this process may occur primarilythrough G�E mechanisms, with some genotypes being more sensitive orsusceptible than others to parenting. As before, we do not rule out the impactof rGE on emotionality, but suggest that, to the extent that emotionality is afunction of genotype, rGE may influence emotionality in the direction of stability.Next we review evidence for the association between specific genotypes andelements of infants’ emotionality, followed by evidence for interactions betweengenes and parenting on developing emotionality. Fundamental to this discussion isthe supposition that emotion reactivity and emotion regulation are criticalprocesses involved in human adaptation that influence individuals’ interactionswith the social environment.

Genetics of Infants’ Emotionality

Using a molecular genetics approach, which attempts to make associationsbetween complex behavioral traits and specific genes that regulate neurotrans-mitter systems, the first step in understanding the genetic underpinnings of infantemotionality has been through an examination of the genes commonly associatedwith adult personality characteristics. Several recent studies have investigated theseassociations in samples of infants and young children, however, many questionsremain regarding the pathways between these genes and the physiological andbehavioral characteristics to which they are linked. The following discussionoutlines research in this area, with a specific focus on two of the most commonlystudied genes in relation to infant and adult behavior: dopamine and serotonin.

Dopamine

Dopaminergic system genes have been the most consistently studied in relation tobehavior, personality, and temperament. Dopamine has been suggested as an


underlying neurotransmitter influencing the behavioral system of approach (Clo-ninger, 1987; Gray, 1982; Zukerman, 1994) and the activation and intensity ofphysiological responses in reward situations (Panksepp, 1986). In adults (Benjaminet al., 1996; Ebstein, et al., 1996) and animals (Bailey, Breidenthal, Jorgensen,McCracken, & Fairbanks, 2007; Grandy & Kruzich, 2004; Livak, Rogers, &Lichter, 1995) specific polymorphisms of dopamine genes have been related tohigher levels of novelty seeking and exploratory behavior.

One of the first groups to look at a dopamine gene in relation to emotionality inan infant sample examined the D4 dopamine receptor gene (Auerbach, Faroy,Ebstein, Kahana, & Levine, 2001; Auerbach et al., 1999; Ebstein et al., 1998). Thisgene contains a repeated sequence polymorphism (i.e., variations in DNA) withinits coding sequences that changes the length of the receptor protein, which hasbeen shown to have functional significance (Asgahari et al., 1994). There is a longpolymorphism (L-DRD4; 6-8 repeats or presence of 7-repeat allele) and a shortpolymorphism (S-DRD4; 2-5 repeats or absence of 7-repeat allele); the shorter theallele, the more efficient the receptor is in binding dopamine (Plomin &Rutter, 1998). Infants with the long polymorphism of DRD4 (L-DRD4) wererated as lower on negative emotionality and distress to limitations at 2 months ofage (Ebstein et al., 1998) and exhibited lower levels of anger-related negativeemotionality at 12 months of age (Auerbach et al., 2001) than those possessing theshort polymorphism of DRD4 (S-DRD4). Furthermore, at age 12-months, infantswith L-DRD4 also showed higher levels of activity during a free play situation thanthose with S-DRD4. In sum, this line of research found that infants possessing thelong version of the DRD4 gene were less negative, not as easily distressed, andmore active than those with the short version of this gene, suggesting (as does theadult literature) that this gene may be related to exploratory or stimulus-seekingbehavior even before the age of one. Similarly, other studies in children have foundassociations between L-DRD4 and approach, or novelty-seeking, behaviors such asexternalizing problems (LaHoste et al., 1996; Sunohara et al., 2000), oppositionaldefiant behaviors (Kirley et al., 2004), and aggression (Schmidt, Fox, Rubin, Hu, &Hamer, 2002).

Serotonin

Another neurotransmitter that has been found to be linked to human behavior andemotion is serotonin. The human serotonin transporter (5-HTT) gene has apolymorphism in the promoter region called the serotonin transporter gene-linkedpolymorphic region (5-HTTLPR), which has been associatedwith the regulation ofmood and emotional states in adults (see review in Westernberg, Murphy, & DenBoer, 1996) through inhibition of behavioral and emotional responses(Sourbrie, 1986). Human adult studies have found that low levels of serotoninare associated with depression, alcohol abuse, impulsivity, risk taking, aggression,


and difficulties in regulatory and emotional functioning (Barr et al., 2004;Suomi, 2000). The serotonin transporter gene has also been associated with with-drawn behaviors and anxiety-related symptoms (Lesch et al., 1996). Studies illustratethat there is less gene transcription, and therefore less protein production, inindividuals with the short allele (s) than the long allele (l) of the serotonin transportergene (5-HTTLPR) (Greenberg et al., 1999; Heinz et al., 2000; Lesch et al., 1996).Therefore, low 5-HTTLPR expression may lead to lower serotonergic function.

Initial studies looked at bivariate associations between serotonin and infant andchild behavioral functioning. Findings of one study revealed that the short allele ofserotoninwas associatedwith shyness in third and fourth grade children (Battaglia etal., 2005). Similarly, preschool-aged children carrying the short alleles of the5-HTTLPR gene were also rated (by mothers) as significantly shyer than thosecarrying at least one of the long alleles (Hayden et al., 2007). These findings,consistentwith the adult literature, confirm the role of this genotype inmechanismsof emotion reactivity and regulation related to internalizing types of behaviors.

Although studies of dopamine and serotonin in infants and children haverevealed some interesting links that parallel work in the adult and animal literature,there have beenmanymixed results and failed replications. For example, one studyfound the opposite association between L-DRD4 and aggressive behavior in 6-year-old children than the ones reported above (i.e., elevated externalizing problemscores in the absence of L-DRD4; Birkas et al., 2005). Similarly, several studies havefound no relationship between the short allele of serotonin and shyness or otherinternalizing behaviors in children (Arbelle et al., 2003; Schmidt et al., 2002; Young,Smolen, Stallings, Corley, & Hewitt, 2003). These studies share a commonlimitation, namely the adoption of a main effects modeling approach in whichpolymorphisms were used as predictors of behavioral outcomes without con-sideration of relevant experience or other genetic effects.

Gene x Parenting Interactions

These initial studies are important in that they identify candidate genes for variousemotional characteristics in infants and young children, however, these studieslooked at genes in relation to outcomes without taking environmental factors intoaccount. Although identifying associations between a specific gene and outcome isan important starting point, it is becoming increasingly clear that it is impossible tounderstand genetic effects without taking into account environmental factors andlife experiences. This limitation may be one reason for mixed results and failedreplications in the literature.

For example, one line of research found that as early as 1-month of age, infantspossessing the L-DRD4 genotype exhibited significantly less difficulty in modifyingtheir reactions to a change in stimuli (i.e., adaptation, perhaps a rudimentaryform of emotion regulation), such as objects, food, or clothes, than those with the


S-DRD4 form (DeLuca et al., 2001). However, a follow-up study at 5-months-old,and again at 3-years-old, evaluated individual differences in adaptability behaviorand results at both time points failed to find an association between the DRD4polymorphism with the measured trait (DeLuca et al., 2003). Although there wasnomain effect of DRD4 at the two later time points, the possibility of an interactionwith parenting cannot be ruled out. Over time, infants’ increased interactions withthe external environment and their caregivers may provide the necessary experi-ence to effect change in genetic expression.

The first studies that examined gene by environment interactions were con-ducted with non-human animals and human adults. Several studies found thatrhesus monkeys who possessed the short allele of serotonin and were raised bypeers, rather than their mothers, exhibited more behavioral and physiologicalproblems (i.e., aggression, alcohol consumption, stress reactivity) than those whodid not possess the short allele (Barr et al., 2004; Bennett et al., 2002). Similarly,Caspi et al. (2003) found that adults carrying the short allele of serotoninweremorelikely to be depressed when they experienced stressful life events than adultswithout the short allele or those with the short allele who did not experiencestressful life events.

Recent research of infant and child emotionality has examined interactionsbetween genes and parenting and found consistent results across studies. Theinteraction of the L-DRD4 polymorphism and insensitive maternal caregivingduring infancy predicted increased externalizing behaviors, including oppositionaland aggressive behaviors, in preschool-age children (Bakermans-Kranenburg&vanIJzendoorn, 2006). Consistent with this research, the interaction of S-DRD4 andhigher maternal warm-responsive parenting in another recent study predicteddecreased externalizing behavior in African American children by 30months of age(Propper et al., 2007). A third study that examined these relations in youngerchildren found that children 18–21 months of age possessing the L-DRD4 poly-morphism who received lower quality parenting were reported, by caregivers, asexhibiting more sensation seeking behavior than children with the L-DRD4 allelewho received higher quality parenting (and those children with the S-DRD4 andhigh or low quality parenting) (Sheese, Voelker, Rothbart, & Posner, 2007).Interestingly, those children with the L-DRD4 polymorphismwho received higherquality parenting were reported to have the least sensation seeking behavior of allthe groups. Furthermore, childrenwho did not possess the L-DRD4 polymorphismwere unaffected by parenting, potentially providing support for the differentialsusceptibility hypothesis discussed above.

Similar studies of the interaction between the serotonin gene and the earlycaregiving environment have been done in samples of children, although, to date,none have examined serotonin-parenting interactions in infancy. One study foundthat observed behavioral inhibition andmother- reported shyness in children wereassociated with the short allele of 5-HTTLPR only when families reported lowlevels of social support (Fox et al., 2005), which is associatedwith greater difficulties


in parenting. Stein, Schork, and Gelernter (2007) found that children whoexperienced emotional or physical maltreatment, and were homozygous for theshort allele of 5-HTTLPR, displayed higher levels of anxiety-sensitivity than thosewithout the short allele. Consistent with that research, Kaufman et al. (2004) foundthat maltreated children with two short alleles (s/s) of 5-HTTLPR and no positivesupport, from parent, relative, other adult, or friend, scored almost twice as high ondepression ratings as those possessing the long allele, or those with the s/sgenotype and positive support. Finally, in a non-risk sample, an interactionbetween serotonin and attachment security predicted electrodermal reactivityduring a psychosocial stress task in 7-year-old children (Gilissen, Bakermans-Kranenburg, van IJzendoorn, & Linting, 2008). Although no direct associationwas found between 5-HTTLPR and electrodermal reactivity in that study, childrenwith secure attachment relationships who also possessed two long alleles of5-HTTLPR (l/l) experienced less stress than did children in every other geno-type/attachment group (i.e., short allele/secure, short allele/insecure, long allele/insecure).

In summary, these findings provide consistent evidence for the importance ofparenting as a moderator of genetic effects on behavioral and physiological indicesof infant emotionality. An important next direction in the study of gene-parentinginteractions is to understand the mediating mechanisms by which parenting maymoderate genetic effects. We propose that, in infancy, parenting may moderategenetic effects through its impact on infants’ developing physiological systems ofemotion reactivity and emotion regulation. In the next section, we discuss researchsupporting this theory. First we discuss research that describes the physiologicalbasis of infant emotionality. Then we provide evidence for parenting effects oninfant emotionality and for genetic effects on infant emotionality. Finally, wediscuss research on gene-parenting interactions in the study of infants’ physiolo-gical mechanisms of emotionality.

Infant Emotionality and Physiological Responses

In infancy, much of the research on physiological processes associated with infants’temperament and emotionality has focused on vagal tone functioning. The termvagal tone refers to control of the heart via the vagus nerve and is typicallymeasured as the amplitude of respiratory sinus arrythima (RSA), which representsparasympathetic influence on heart rate variability (Porges, 1996; Porges &Byrne, 1992). The vagal system has been suggested as one possible biologicalsubstrate for regulation of arousal state and reactivity underlying individualdifferences in temperament (Fox & Stifter, 1989; Stifter, 1995; Stifter & Fox, 1990;Stifter, Fox, & Porges, 1989). In the extant literature, RSA is commonly equatedwith vagal tone, however, it is important to remember that RSA is only one


component of vagal tone and that there are many other influences on heart ratevariability (Grossman & Taylor, 2007). Of these various components, however,RSA has been the most consistently examined in relation to dimensions oftemperament and emotionality in infants.

Baseline RSA

Baseline or resting RSA is considered to be a stable neurophysiological mechanismunderlying autonomic and behavioral reactivity that provides a measure of thepotential capacity of the system to react to emotion eliciting stimuli, with higherbaseline RSA indicating flexibility and greater capacity to respond. Baseline RSA isalso thought to reflect an infant’s regulatory capacity, independent of caregivers’assistance, to return to behavioral and physiological homeostasis after a stressor(Porges, 1996). Research has explored the relationship between baseline RSA andinfant emotionality during positive, novel, andmildly stressful situations and foundpositive correlations between the two measures.

Developmentally, neonates who cried in response to pacifier withdrawal hadhigher restingRSA than thosewho did not cry and, at 5months,weremore likely tocry in response to arm restraint (Stifter & Fox, 1990). Five-month-old infants whocried in response to arm restraint had higher resting RSA than those who did notcry, and infants who cried as neonates and at 5 months in response to stressors hadhigher resting RSA than infants who cried at neither age, and they were rated bytheir mothers as being more easily distressed by limitations (Stifter & Fox, 1990).Similarly, at 14, 20, and 26weeks of age, infants with higher baseline RSA tended tobe more behaviorally reactive (DiPietro, Larson, & Porges, 1987; Porges,Doussard-Roosevelt, Portales, & Suess, 1994) and exhibited more frequentapproach behaviors. This work suggests that, in early infancy, higher resting RSAis associated with behavioral indices of negative emotionality, greater emotionreactivity, and temperamental difficulty.

However, longitudinal investigations have identified shifts in associationsbetween RSA and functional behaviors. Although Stifter and Fox (1990) observedthat at 5 months of age, negative behavioral reactivity to arm-restraint occurredmore quickly and intensely in infants with higher RSA than those with lower RSA,at 14 months of age, during an interaction with an unfamiliar adult, infants withhigher RSA showed more positive approach behaviors towards the stranger andtowards a novel toy than infants with lower RSA. One explanation for theunexpected findings that higher RSA is associated with negative emotionality andreactivity at 5 months and with positive and sociable behavior at 14 months is thatparenting modified the expression of infants’ temperamental emotionality overtime. Young infants with higher RSAmay react more strongly to emotion-elicitingstimuli in the early months of life and influence the way in which their caregiversrespond to them, an example of evocative rGE.Highly reactive infants that respond


appropriately to aversive stimuli (with distress and crying) may be better able tosignal their caregivers and receive the parenting support that they need, whichmaylead to more socially appropriate and effective behavioral expressions of emotion-ality later in development.

An alternate interpretation is that the different contexts at the two different agesaccount for the findings, with infants with high RSA showing themore appropriateand effective responses for the specific context at each age, regardless of interveningparenting. Measures of parenting in longitudinal research examining the associa-tions between infants’ physiological functioning and observed emotionality areneeded to clarify the meaning of these findings.

There is consistent evidence of a normative developmental increase in meanlevels of baseline RSA as physiological systems becomemore organized over time.Research has shown that mean baseline RSA increases from infancy throughmiddle childhood (Bornstein & Suess, 2000; Izard et al., 1991; Porges et al., 1994;Richards & Cameron, 1989; Stifter et al., 1989). However, there is inconsistentevidence for stability of baseline RSA over time. Several studies have found nostability over the first year of life (Porter, Bryan,&Hsu, 1995; Stifter et al., 1989), yetother studies have reported stability from 3 months to 3 years of age (Izardet al., 1991; Porges et al., 1994; Porter et al., 1995), and moderate stability from 4months to 4 years of age (Bar-Haim, Marshall, & Fox, 2000). Once more, thesemixed findings may be due to the lack of attention given to the influence thatexperience in parent-infant relationships exerts on the developing physiologicalsystems from birth onward that may help to maintain or modify existing RSAresponse patterns.

RSA Reactivity

Vagal tone functioning represents a dynamic physiological process. Because of this,measures of RSA are sensitive to environmental demands or challenge.Porges’ (2007) polyvagal theory of social engagement asserts that the autonomicnervous system enhances restoration and growth by regulating the “vagal brake,”which slows down the heart (i.e., activated vagal tone) during situations that donot present a challenge or in some contexts that elicit calm, focused attention.A decrease in RSA, or RSA withdrawal, however, typically occurs when anindividual is involved in an activity that requires active coping (Porges,1991, 1996), at which time the vagal “brake” is withdrawn (i.e., vagal tone isinhibited) to support an increase in heart rate.When environmental demands haveceased, the brake is reengaged (i.e., vagal tone is activated) to promote decreases inmetabolic output and a return to a calm state. Thus, effective RSA reactivity hasbeen related to the ability tomaintain homeostasis in the face of changing demandsby allowing a shift from attention on internal demands to external ones that includethe use of coping strategies to regulate affective or behavioral arousal.


RSA reactivity in terms of RSA withdrawal during a challenging situation hasbeen related to positive outcomes in infants and children, including highersoothability (Huffman et al., 1998), more attentional control (Huffman et al., 1998;Suess, Porges, & Plude, 1994), and better emotion regulation (Calkins, 1997). Onestudy of 9-month-olds found that infants with lower levels of RSA withdrawalduring a social/attentional task exhibited more behavioral problems at 3 years ofage than peers who showed higher levels of RSA withdrawal (Porges, Doussard-Roosevelt, Portales, & Greenspan, 1996). Thus, Posner and Rothbart (2000)asserted that dynamic RSA reactivity may be an index of social and attentionalcontrol that underlies the behavioral strategies necessary for regulation of emo-tionality. Although supporting data (Bazhenova, Plonskaia, & Porges, 2001; Moore& Calkins, 2004) are not conclusive, empirical research has led to the assumptionthat greater RSA withdrawal during a challenge condition reflects more effectivedynamic regulation, whereas, as previously discussed, baseline RSA reflects thepotential capacity of the individual to respond effectively.

Parenting, Infants’ RSA Regulation, and Emotionality

In early infancy, caregivers facilitate physiological homeostasis as they assistinfants in attaining a balance between endogenous needs and exogenousstimuli (Hofer, 1987). Due to the rapid amount of neurological growth duringthis stage, parenting may have long-term effects on development of physiologicalsystems related to emotionality (Black & Greenough, 1986; Cichetti &Lynch, 1995). The way in which caregivers respond to the needs of their infantsmay have an impact on infants’ ensuing abilities to modulate physiologicalreactivity and developmore adaptivemethods of regulation over time (Derryberry& Rothbart, 1984).

RSA functioning, therefore, is a potential mediator of the relation betweenparenting and changes in the expression of infant emotionality across development.A number of studies have explored developing patterns of RSA functioning inrelation to qualities of parent-infant interaction. Infants of dyads that spent moretime in joint communicative states with responsive adjustment to each other’sbehaviors, had higher baseline RSA than those in dyads that did not display thispattern ofmutual dyadic regulation (Porter, 2003).Moore andCalkins (2004) foundthat as early as 3 months of age, infants of dyads exhibiting lower behavioralsynchrony showed higher RSA withdrawal during a normal play episode and lessRSA withdrawal during a situation meant to elicit distress, both of which wereatypical responses. Following an experimentally disrupted social interaction at6months of age (the still-face procedure), only infants of sensitivemothers and theirmothers showed a significant decrease in RSA from baseline, suggesting thattheir mutual RSA withdrawal may have been a function of mutual behavioral


responsiveness and that both were equally active and engaged in repairing theirsocial interaction (Moore et al., 2009).

Attachment theorists (e.g., Cassidy, 1994) propose that the attachment relation-ship consolidates, over time, the behavioral and physiological responses used byinfants to successfully interact and cope with stress within the parent-childrelationship. Consistent with this theory, infants classified as insecure-avoidantdisplay greater cardiac arousal and RSA withdrawal during separation and reunionepisodes of the Strange Situation procedure than do infants classified as securelyattached (Hill-Soderlund et al., 2008). According to attachment theory, a mismatchbetween a high level of RSA withdrawal and a low level of observed behavioraldistress may occur if infants have developed the need to rely on self-regulationrather than caregiver support for regulation of distress.

Support for the theory that parenting influences the consolidation of infants’physiological regulation extends into toddlerhood. In a sample of two-year-olds,maternal negative control was associated with lower infant RSA withdrawal in anemotion-eliciting task, reflecting less effective physiological regulation (Calkins,Smith, Gill, & Johnson, 1998). The authors proposed that children with morecontrolling mothers may be less able to regulate their own physiological arousalbecause they are accustomed to receiving high amounts of external regulation orare not exposed to a range of effective regulatory strategies for use in differentsituations. Alternatively, mothers may exert more negative control with childrenwho have difficulty regulating their emotions, another example of evocative rGE.Cross-sectional studies of biological families are unable to disentangle these variousinterpretations.

Longitudinal research, however, does provide evidence for the influence ofearly parent-infant relationships on later physiological functioning. Burgess,Marshall, Rubin, and Fox (2003) found that, although attachment classificationat 14 months of age was not concurrently associated with heart period or baselineRSA, it did predict these autonomic measures at 4 years of age. More specifically,children classified as having insecure-avoidant attachment relationships, assessedat age 14 months, had significantly higher heart period (i.e., lower heart rate)and higher baseline RSA at 4 years than did children classified as having secure orinsecure-ambivalent relationships. One possible explanation for this change maybe that hyperactivation of the vagal system in early infancy, due to the lack ofcaregiver support for infant regulation, may lead to a “burn out” phenomenon(see Hill-Soderlund et al., 2008). As described above, infants classified as insecure-avoidant may regulate their own distress, rather than openly communicate totheir caregivers, which may be more physiologically challenging (e.g., Hill-Soderlund et al., 2008; Spangler & Grossman, 1993). Although in the short termthis may be an adaptive response, this increased physiological load may lead topoor functioning in the long term. As the infant matures, the vagal systemmay become autonomically under-reactive, which may in turn lead to under-controlled behaviors.


Physiological regulatory fatigue has been demonstrated in adults over shortperiods of time in conditions that require self-control (Muraven & Baumeister,2000; Muraven & Slessareva, 2003), suggesting that chronic activation of self-regulatory mechanisms could lead to a diminished reactivity and also detract fromresources that could be utilized to promote optimal social and cognitive devel-opment. Prospective longitudinal work is valuable in that it supports the possibilitythat autonomic functioning at age 4 may be the result of, rather than the cause of,the quality of parent-child relationships.

Depression

Mothers with high levels of depressive symptoms are less likely to providecontingent responsive behavior towards their infants during interactions (Field,Healy, Goldstein, & Guthertz, 1990; Forbes, Cohn, Allen, & Lewinsohn, 2004), inpart due to less matching of affective states and more matching of negativestates (Cohn, Campbell, Matias, & Hopkins, 1990; Field et al., 1990). Motherswith higher levels of depressive symptoms have been found to display lowerlevels of synchrony during face-to-face interaction with their infants than othermothers (Moore & Calkins, 2004). Compared to other infants, infants ofmothers with higher levels of depressive symptoms may receive less positivefeedback, less exposure to a range of emotions, or may need to do more work toengage their mothers, which in turn may create long term changes in the vagalsystem. This type of interaction may inhibit the development of behavioraland physiological responses necessary for effective emotion regulation. Consistentwith this theory, infants of depressed mothers did not show the normativeincrease in baseline RSA between 3 and 6 months of age (Field, Pickens, Fox,& Nawrocki, 1995).

Maternal depression is associated with several influences, including genetic andprenatal factors, that may affect offspring. Future research should examine infantemotion development in a way that differentiates impaired neurological function-ing due to such genetic or prenatal circumstances from long term changes thatmayoccur due to parenting.

Parent Conflict

In older children, vagal regulation is related to behavioral adjustment to conflictbetween parents. Higher measures of RSA withdrawal appeared to buffer childrenfrom the negative effects of inter-parent conflict (Katz & Gottman, 1997) and arelation between high levels of inter-parent conflict and child externalizingbehaviors was found for children with low baseline RSA, but not for childrenwith high baseline RSA (Katz & Gottman, 1995). These results were replicated and


extended to show that higher baseline RSAmoderated relations between exposureto inter-adult conflict and child internalizing behavior problems and healthproblems (El-Sheikh, Harger, & Whitson, 2001).

Only two studies of which we are aware have examined infants’ RSA in relationto parent conflict. The first found that 6-month-old infants in families reportinghighermarital conflict showed lower baseline RSA, suggesting a decreased capacityfor effective regulation (Porter, Wouden-Miller, Silva, & Porter, 2003). In thatstudy, infants with lower baseline RSA also showed lower levels of behavioralregulation as assessed by the Behavior Rating Scales (Bayley, 1993). In a secondstudy, 6-month-old infants in higher conflict families showed diminished RSAwithdrawal in a challenge condition relative to other infants and unexpected RSAwithdrawal when interacting withmothers (Moore, 2010), although no differencesin baseline RSA. This pattern of findings suggests atypical RSA regulation and areliance on self-regulation for infants in families with moderate levels of parentconflict. In contrast, Gottman and Katz (1989) found that preschool-aged childrenin families reporting greater parent conflict showed higher RSA than otherchildren. Gottman and Katz (1989) proposed that this unexpected finding repre-sented a temporary adaptation that, over the course of development, couldoverburden children’s capacities for self-regulation.

Exposure to parent conflict may increase demands on infants to regulate arousaland/or higher conflict between parents in a family may diminish parents’ abilitiesto respond sensitively to their infant’s need for support in regulating behaviorand emotions, requiring the child to become more dependent on self-regulation(e.g., Davies & Cummings, 2006; Donovan, Leavitt, & Walsh, 1998). Morefrequent demands to regulate arousal and the necessity of relying on self-regulationcould either overwhelm infants’ rudimentary abilities to regulate RSA, consistentwith the regulatory fatigue theory discussed earlier (Muraven & Baumeister, 2000;Muraven & Slessareva, 2003). Thus, as Gottman and Katz (1989) suggested, apattern of RSA regulation that may be an effective adaptation in early childhood,with time could become a maladaptive regulatory response.

On the other hand, the physiological toughness model (Dienstbier, 1989;Dienstbier & Zillig, 2002) proposes that experiencing intermittent and mild tomoderate stress has a beneficial effect on some biological systems. Dienstbier(1989), for example, found that the neuroendocrine system increases availability ofepinephrine under intermittent and moderate stress conditions, which protectsagainst depletion of epinephrine when the individual encounters more intense ormore chronic stressors in the future. Therefore, increased frequency of the need toemploy RSA regulation and a need to rely more on self-regulation than externalsupport from parents, which may occur in environments with higher parentconflict, could facilitate the effectiveness of a child’s RSA functioning, particularlyif he or she is living in an environment where conflict is mild but common. Thiscould explain why some children develop effective RSA regulation in families withhigh conflict, which then buffers them from negative behavioral outcomes


typically associatedwith parent conflict later in development (El-Sheikh et al., 2001;Katz & Gottman, 1995, 1997).

It is also possible that infants’ difficulty regulating their own emotionmay lead toparental irritability, creating more stress within the marital relationship (evocativerGE), or that parents who have difficulty regulating their own emotions andthus engage in more conflict have infants who have inherited a physiologicalvulnerability to problems with emotion regulation (passive rGE). Consistent withthis, a study using the Children of Twins design found that genetic influencesmediated the association between marital conflict and conduct problems (Hardenet al., 2007).

In summary, the importance of the parent-infant relationship as an agent ofchange in infant emotionality over time has been supported by numerous studiesutilizing a variety of research designs, including longitudinal, at-risk samples, andtwin studies. However, it is less clear from that body of researchwhether parentingmodifies physiological mechanisms or behavioral expression of emotionalityrelated to these physiological mechanisms. Research is needed to clarify thoserelations. In addition to understanding whether parenting serves as an environ-mental influence on the development of infants’ emotion reactivity and regulation,it is important to also consider the genetic contributions to these physiologicalmechanisms, and how genetic processes and parenting interact.

G � E (Parenting) Predictors of RSA

A recent study provides support for the importance of this approach by taking intoaccount the effect of both genotype and infant-caregiver relationships on physio-logical change over time. Findings revealed that the direct effect of the dopaminereceptor gene D2 (DRD2) on infant physiological responses to stress changedover the first year of life in relation to infants’ experiences with caregivers (Propperet al., 2008). At 3 and 6 months of age, infants with the taq1 A1 polymorphism ofthe DRD2 gene, which has been found in adolescents and adults to be associatedwith impulse control problems and sensation seeking behaviors, did not exhibitexpected physiological regulation during an age-appropriate stressful situation(i.e., separation from mother) as measured by vagal reactivity (i.e., decrease inrespiratory sinus arrhythmia, or RSA). However, results revealed that maternalcaregiving behavior moderated the change in RSA response to stress by 12 monthsof age. Those infants possessing the taq1 A1 polymorphism of DRD2, who werealso exposed to sensitive maternal caregiving over the first year of life, exhibited amore optimal and expected RSA response to stress at 12months of age, comparableto the RSA reactivity of those infants possessing the non-risk version of the gene. Atthis time, this study is the only one of which we are aware that has looked at theinterplay of genes and parenting as predictors of RSA reactivity in infants.


However, these findings provide a promising new direction for examiningindividual differences in trajectories of physiological functioning. Furthermore,studies such as this one contribute to our understanding of the origins of infanttemperament through the identification of specific genes and parenting behaviorsthat influence infant physiological processes associated with emotion reactivityand regulation.

Conclusion

In summary, recent studies have made great strides towards understanding theorigins of infant temperament and emotionality. Although there have beennumerous studies of the influence of parenting and genetics on infant behaviorand physiology,many questions still remain. The developmental systems approachthat we have described here seeks to examine infant behavioral and physiologicalphenotypes by taking into account all of these predictors through the explorationof the interplay between specific candidate genes and the environment (i.e., infant-parent relationship) over time. This multi-level methodology has yielded someexciting results and has provided a new and encouraging direction for research oninfant temperament. Extant research has supported the theory that parentingbehavior may moderate genetic effects on temperament, whether directly viabehavior or through the impact on the endophenotypic development of physio-logical systems, as we have proposed, leading to individual differences in emotionreactivity and regulation.

The univariate approach (studying only genes or environment or using singlemeasures as outcomes) that has often been used in the past to predict complexbehavioral and physiological outcomes is oversimplified. In order to truly under-stand the contributing mechanisms and developmental pathways of infant beha-vior and physiology over time, we must begin to examine in one model relationsbetween infant behaviors (reactivity and regulation), multiple candidate genes,multiple measures of autonomic and neuroendocrine functioning (e.g., vagal tone,cortisol, alpha-amalyase), and neurological variables (e.g., assessed via ERP, EEG),along with sophisticated measurement of the environment. Future researchusing this developmental systems approach could become increasingly productiveby incorporating even more precise measurement at various levels (Mooreet al., 2009). Global ratings or self-reports of parenting are likely to provide lessmeaningful measures of the environment when analyzed in relation to specific,dynamic physiological processes of infant functioning, as global ratings andself-reports of parenting tend to reflect trait-like characteristics of parents ratherthan reflecting a parent’s unique responses to an individual child’s behavior in aspecific context. On a different temporal scale, the same properties that Gottliebdescribes as emerging across development from coactions among environmental,


behavioral, neural, and genetic levels (Gottlieb, 1991, 1998; Gottlieb &Halpern, 2002) may also occur in the everyday, moment-to-moment interactionsbetween parents and children.

Furthermore, it has become increasingly clear that the study of gene-environ-ment correlations and interactions is an integral part of understanding develop-mental outcomes. The conceptual differentiation of the statistical term, interaction,from the epigenetic term, coaction, is particularly important in this regard. To thiseffect, appreciating that the notion of risk and resiliency must be understood asproperties of gene-environment coaction, rather than of individual genotypes andenvironments, is paramount for understanding and accurately representing thecomplexities of infant temperament and emotion development. As describedpreviously in this chapter, it is important to remember that child genotype andparental behavior are both part of one family (Cox & Paley, 2003) and onedevelopmental epigenetic (Gottlieb, 1998) system. Only when our theoretical andmethodological approaches achieve sufficient sophistication to incorporate multi-ple relations across time will we better model the dynamic complexity ofdevelopment.

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