Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior.
Journal: 2006/January - Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
Abstract:
The formation of social attachments is a critical component of human relationships. Infants begin to bond to their caregivers from the moment of birth, and these social bonds continue to provide regulatory emotional functions throughout adulthood. It is difficult to examine the interactions between social experience and the biological origins of these complex behaviors because children undergo both brain development and accumulate social experience at the same time. We had a rare opportunity to examine children who were reared in extremely aberrant social environments where they were deprived of the kind of care-giving typical for our species. The present experiment in nature provides insight into the role of early experience on the brain systems underlying the development of emotional behavior. These data indicate that the vasopressin and oxytocin neuropeptide systems, which are critical in the establishment of social bonds and the regulation of emotional behaviors, are affected by early social experience. The results of this experiment suggest a potential mechanism whose atypical function may explain the pervasive social and emotional difficulties observed in many children who have experienced aberrant care-giving. The present findings are consistent with the view that there is a critical role for early experience in the development of the brain systems underlying basic aspects of human social behavior.
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Proc Natl Acad Sci U S A 102(47): 17237-17240

Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior

Department of Psychology, University of Wisconsin, 1202 West Johnson Street, Madison, WI 53706-1696; Waisman Center for Human Development, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705; Wisconsin National Primate Research Center, 1220 Capitol Court, Madison, WI 53715; and Molecular and Environmental Toxicology Center, University of Wisconsin, 777 Highland Avenue, STE 2233, Madison, WI 53705-2222
To whom correspondence should be addressed. E-mail: ude.csiw@kallops.
Edited by William T. Greenough, University of Illinois at Urbana-Champaign, Urbana, IL
Edited by William T. Greenough, University of Illinois at Urbana-Champaign, Urbana, IL
Received 2005 Jun 7; Accepted 2005 Sep 20.

Freely available online through the PNAS open access option.

Abstract

The formation of social attachments is a critical component of human relationships. Infants begin to bond to their caregivers from the moment of birth, and these social bonds continue to provide regulatory emotional functions throughout adulthood. It is difficult to examine the interactions between social experience and the biological origins of these complex behaviors because children undergo both brain development and accumulate social experience at the same time. We had a rare opportunity to examine children who were reared in extremely aberrant social environments where they were deprived of the kind of care-giving typical for our species. The present experiment in nature provides insight into the role of early experience on the brain systems underlying the development of emotional behavior. These data indicate that the vasopressin and oxytocin neuropeptide systems, which are critical in the establishment of social bonds and the regulation of emotional behaviors, are affected by early social experience. The results of this experiment suggest a potential mechanism whose atypical function may explain the pervasive social and emotional difficulties observed in many children who have experienced aberrant care-giving. The present findings are consistent with the view that there is a critical role for early experience in the development of the brain systems underlying basic aspects of human social behavior.

Keywords: attachment, emotion, oxytocin, vasopressin, child abuse
Abstract

The social attachments formed between human infants and their caregivers begin very early in postnatal life and play a critical role in children's survival and healthy adaptation. Typically, adults provide infants with a social environment that is fairly consistent. Caregivers learn how to recognize and respond to the infants' needs, thereby creating predictable contingencies in the environment; these regularities, in turn, make the infant's environment secure and conducive to further social learning (1, 2). Multiple perceptual, sensory, cognitive, and affective systems must become synchronized so that a social bond can develop between an infant and caregiver; this bond is then reflected in the child's adaptive behavioral responses to the environment. The goal of this experiment was to address a fundamental evolutionary and developmental question: To what extent are the neurobiological systems that regulate affiliative behaviors dependent on the social experiences afforded to most infants by their caregivers?

It is difficult to evaluate the effects of early social experience on the organization of the developing brain because, within seconds of postnatal life, the human infant experiences a vast amount of emotional input. In this regard, the maturation of the brain is confounded with the accumulation of social experience. One way to address this problem is to experimentally manipulate the social environment. Although this approach is successful with nonhuman animals, such studies are neither possible nor desirable to undertake with human children. Therefore, to examine the effects of early experience on emotional development, we studied a sample of children who did not receive the kind of emotionally responsive care-giving typically received by human infants. These children were reared in institutionalized (orphanage) settings, where a prominent lack of emotional and physical contact from caregivers is a consistent adverse feature of the environment (3). Previously institutionalized children frequently experience problems in establishing social bonds and regulating social behavior, including a lack of developmentally appropriate wariness of strangers, atypical and disinhibited patterns of attachment, and difficulties developing close friendships (4-6). Fortunately, when these children are adopted, they move into family environments that provide normative contexts for child development. In this regard, children's adoption marks a dramatic (and measurable) termination of social deprivation that allows us to assess the impact of a circumscribed period of early neglect on the neurobiological mechanisms implicated in the regulation of emotional behavior.

To explore the neurobiological mechanisms underlying the formation of social attachments, we examined the oxytocin (OT) and arginine vasopressin (AVP) neurohypophyseal peptide systems in previously institutionalized children. We chose to study OT (7-12) and AVP (13-16) based upon research with nonhuman animals and humans suggesting that these systems are an integral part of mammalian emotional circuitry. These neuropeptides are associated with the emergence of social bonding, parental care, stress regulation, social communication, and emotional reactivity (17-22). OT and AVP levels are increased by socially pleasant sensory experiences, such as comforting touches and smells. Studies with nonhuman animals have demonstrated that as levels of these hormones rise, animals increase their positive social interactions: they form social bonds (23-25), display selective infant-parent attachments (26, 27), and form memories of these social interactions (28). OT receptors are part of the neural system of reward circuitry that includes the nucleus accumbens (29); a critical feature of this system for infant development is that it likely confers a sense of security and protection that makes social interactions rewarding. Indeed, higher levels of OT are associated with decreases in stress (24).

Our goal was to illuminate the role of early social experience in subsequent brain-behavioral development. Little is currently known about how developmental history can influence the organization and functioning of this emotion-regulatory system in humans. However, a growing body of research suggests that early social experience, through changes in corticotrophin-releasing hormone, may alter OT and AVP receptor binding (30-34). Therefore, we predicted that early social experience would influence the feedback loops involving social reward circuitry, thereby affecting the regulatory capacities of the OT and AVP systems. This mechanism would have developmental implications for stress reactivity and behavioral regulation as the infant matures. Toward this end, we compared the children who began their lives in institutionalized settings to a group of children who were raised in typical family environments.

Children were tested in their homes on two occasions. During one visit, children interacted with their mothers, and on the second visit, children engaged in the same physical interactions with an unfamiliar adult female. The order of these visits was counterbalanced. To ensure that the interactions were similar across children and familiar-unfamiliar adult conditions, an animated computer program guided the physical contacts between child and adult in the form of a game. To avoid the stress involved in the physical discomfort of measuring cerebrospinal fluid or blood, we developed a noninvasive procedure to obtain peripheral measures of OT and AVP (see supporting information, which is published on the PNAS web site).

Little is known about the relationship between central and peripheral OT and AVP levels in humans, and available data suggest that the relationship is complex. However, research with nonhuman animals indicates that under certain conditions, central and peripheral release is coordinated (35-37). For example, suckling leads to increases in OT levels both within the CNS and peripherally in rats (38). Similarly, increased central (39) and peripheral (40) OT levels have been demonstrated after exposure to an emotional stressor. Although little is actually known about the peripheral-central relationship of these peptide systems in humans, nonhuman primates reared in socially deprived environments exhibit alterations of the central OT system (41), consistent with the findings reported here with humans.

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Acknowledgments

We thank Christopher Coe, Megan Gunnar, Catherine Marler, Jenny Saffran, and Charles Snowdon for early discussion about this project and helpful comments on a previous draft of this manuscript. This research was funded by National Institute of Mental Health Grant R01 MH 068858 and grants from the Jane Bradley Pettit Foundation and the University of Wisconsin Graduate School (to S.D.P.). Additional support was provided by Waisman Center, University of Wisconsin Core Grant P30 HD03352, National Institute of Mental Health Grant R01 035215 (to Charles T. Snowdon and T.E.Z.), and the National Center for Research Resources-Wisconsin National Primate Research Center Grant 5P51 RR 000167. A.B.W.F. was supported by National Institutes of Health Training Program in Emotion Research Grant T32 MH 18931. The institutional review board of the University of Wisconsin approved this study.

Acknowledgments

Notes

Author contributions: A.B.W.F. and S.D.P. designed research; A.B.W.F., J.R.K., S.J., and S.D.P. performed research; T.E.Z. contributed new reagents/analytic tools; A.B.W.F., T.E.Z., and S.D.P. analyzed data; and A.B.W.F., T.E.Z., and S.D.P. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: OT, oxytocin; AVP, arginine vasopressin.

Notes
Author contributions: A.B.W.F. and S.D.P. designed research; A.B.W.F., J.R.K., S.J., and S.D.P. performed research; T.E.Z. contributed new reagents/analytic tools; A.B.W.F., T.E.Z., and S.D.P. analyzed data; and A.B.W.F., T.E.Z., and S.D.P. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: OT, oxytocin; AVP, arginine vasopressin.

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