Critical Period in Stress Response System Functioning as Influenced by Early Caregiving Experience

Written by: Emiliya Akhundova

Edited by: Julia Holder, William Jang, Xavier Westergaard

Illustrated by: Gefen Mor

Recent literature suggests that there are specified periods in early development of increased brain plasticity, which is the ability of brain networks to mold as a result of growth and remodeling [1]. This challenges previous beliefs about the role of nature and nurture in shaping the adult brain. Disruptions in the physiological response to stress, or the stress response system, have long been attributed to adverse early experiences [2]. New studies are now investigating the critical period for the development of a functional stress response system and the influence of early caregiving experiences during that time [1,2].

As the brain develops, it is shaped by both genetics and external environmental sensory experiences [3]. Adversities during development, especially when combined with genetic factors, can lead to negative outcomes, such as limitations in mental and physical health, and atypical social functioning [4]. The early environment is critical in healthy neurobiological and emotional development, and traumatic experiences can lead to alterations in coping style, emotional regulation, and neurochemistry [4]. Gaining a comprehension of the sensitive period of development is essential to establish windows of opportunity for intervention to better mitigate the consequences of adverse experience [4]. This article explores the relationship between early caregiving during a specified period of development and the subsequent reactivity of the stress response system in adulthood.

Sensitive periods are windows of time in development during which the brain is especially plastic and responsive to the environment, and include critical periods [5]. These developmental landmarks are important in the acquisition of proper cognitive functioning, like social, language and visual skills [6]. While critical periods are a subtype of sensitive period, there are certain factors that make them distinct [7]. Critical periods are more rigid and less forgiving, with well defined, shorter periods of time and sustained, mostly irreversible, consequences of development disturbances [7]. During this time, sensory milestones, including touch, talk, sight, and sound, are necessary for the shaping of the brain [1, 3]. Critical periods linked to sensory systems, such as in the visual and auditory systems, have been well studied [8, 9]. More recently, critical periods have started being classified for the development of social functions [10].

At the onset of a critical period, the developing brain is highly adaptable and needs to experience the aforementioned sensory milestones to establish optimal neural development and function [11]. These experiences morph the brain, laying the foundation for the development of proper functionality, which can be sequentially consolidated through life post-closure of the period [11]. If such experiences are lacking/absent, the formation of the necessary neural representations is significantly limited, and is usually irreversible without medical interventions post-closure [11]. For example, the absence of supportive early caregiving environments leading to functional dysregulation [8].

Early traumas can cause chronic stress in children, leading to emotional, behavioral, and developmental consequences [12, 13]. Developing healthy regulatory stress response systems relies on early attachment—defined as a “psychological connectedness between human beings– and socialization, which provide the framework for the maturation of healthy regulatory stress response systems [14, 15]. Research suggests that disruptions due to trauma in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis, a hormonal stress response system, during development can result in mood disorders or social dysfunction [4]. Understanding the timing of maximal brain plasticity is key to understanding how the environment shapes brain function and for developing therapeutic interventions for those with dysregulated stress responses [4, 16, 17].

Powered by the secretions of various glucocorticoids, which are steroid hormones such as the stress hormone cortisol, our ability to respond to stressful events arises from the functioning along this LHPA axis [18]. In rodents and primates, research shows that the proper development of the LHPA system for functioning in adulthood is molded by early experiences with caregivers [4, 19, 20]. This seems to be similar in humans, whereby adversities in early caregiving experiences predispose individuals to the development of various abnormalities caused by stress sensitivity such as depression and post traumatic stress disorder (PTSD) [21, 22].

The quality of caregiving experience in early childhood is complex and comprises availability, sensitivity, and attentiveness of the caregiver, and it has implications on basal cortisol levels of young children [22]. Rodent models show that supportive caregiving experience establishes lower cortisol levels during early years and in its absence children have elevated glucocorticoids levels that persist into adulthood [23]. Interestingly, children with insecure attachment styles, a negative parent-child relationship characterized by a lack of trust, experience spikes in cortisol during periods of separation with their caregivers, unlike their counterparts with secure attachments, a positive parent-child relationship characterized by confidence and trust, providing further evidence for the effect of caregiving on cortisol signaling as there are differences between the two attachment styles [24-26]. Since insecure attachment is a type of developmental adversity, its harmful effects on hormonal signaling yield further evidence in the context of caregiving as an environmental influence on biological stress buffering.

Studies indicate that social experience in early life is critical for the proper functioning of the LHPA axis in buffering stress response in adulthood [27]. This study shows that proper caregiving experience lowers the ability to elicit heightened cortisol responses in toddlers, preventing spikes in stress hormone signaling. Further the study showed, in cases of abuse causing chronic PTSD, high cortisol levels are closely correlated with the duration of the abuse. Early life social experience regulates cortisol regulation, and without responsible care, proper buffering capacities cannot develop further exacerbating the adult response to stress [27].

A recent breakthrough in establishing a causal relationship between early caregiving experience and the successful maturation of the stress response system came from studying the Bucharest Early Intervention Project (BEIP), where the placement of children into high quality foster care (which stimulated supportive environments) versus institutional rearing (which simulated adverse early experiences) was evaluated [2]. This long-term analysis shed light on the abnormalities of the development of the LHPA axis of children who were exposed to deprivations of caregiving in the form of institutional rearing [2]. In regard to institutionalized care, the central deviation from ‘normal’ experience is the lack of responsiveness and sensitivity caregiving and, in the past, placement into foster care in the BEIP was correlated to higher quality of caregiving and security of attachment in children [28, 29].

The investigators employed the Trier Social Stress Test , which utilizes a social stressor, to evaluate LHPA functionality [2]. By measuring cortisol and another major stress hormone, DHEA-sulfate, the study showed that the deprivation experienced by institutional care children in the BEIP closely resembled adverse early caregiving experiences of neglectful caregivers in animal studies [2, 30]. This indicates that stress response is influenced by early development of stress responsive systems in humans [2].

In observing the timing of placement into foster/institutional care, the researchers were also able to draw conclusions about the presence of a sensitive period in establishing a stress reactivity in children. Earlier age of placement into foster care was correlated with cortisol reactivity that resembled results associated with those that had never been institutionalized [2]. Children placed before 24 months of age in this study exhibited overall significantly higher cortisol reactivity. This result narrows down the timing of the sensitive period to before 24 months in development during which the environment has the strongest influence on the development of stress responses and functioning along the LHPA axis [2].

This study suggests that there is a period of fundamental plasticity which can be negatively impacted by the deprivation of caregiving causing psychological damage [2]. Furthermore, this research supports the importance of placing abandoned children into family care in an effort to minimize the consequence of persistent effects of adverse caregiving experience on healthy stress response.

Future research needs to focus on establishing specific determinants in improving the quality of caregiving experience to ensure the proper maturation along the LHPA axis. Comprehensive insight into the environmental cues which influence this process will allow for the mediation of adverse early life exposures. This research has the potential to not only inform caregiving practices for many abandoned/neglected children but also to shed light on potential remedies to mitigate those consequences.

References

[1] Cisneros-Franco, H.M., Voss, P., Thomas, M. E., Villers-Sidani, E. (2020). Chapter 8 - Critical periods of brain development. Handbook of Clinical Neurology, Elsevier, 173, 75-88.

[2] McLaughlin, K. A., Sheridan, M. A., Tibu, F., Nelson III, C. A. (2015). Causal effects of the early caregiving environment on development of stress response systems in children. PNAS, 112, 5637-5642.

[3] Huberman, A. D., Feller, M. B., Chapman, B. (2008). Mechanisms underlying development of visual maps and receptive fields. Annu Rev Neurosci, 31, 479-509.

[4] Sanchez, M. M., Ladd, C. O., Plotsky, P. M. (2001). Early adverse experience as a developmental risk factor for later psychopathology: Evidence from rodent and primate models. Development and Psychopathology, 13, 419-449.

[5] Knudsen, E. I. (2004) Sensitive periods in the development of the brain and behavior, J Cogn Neurosci, 16, 1412-25.

[6] White, E. J., Hutka, S. A., Williams, L. J., Moreno, S. (2013) Learning, neural plasticity and sensitivity periods: implications for language acquisition, music training and transfer across the lifespan, Front Syst Neurosci, 7, 90.

[7] Oyama, S. (1979) The Concept of the Sensitive Period in Developmental Studies. Merill-Palmer Quarterly of Behavior and Development, 25, 83-103.

[8] Hubel, D. H., Wiesel, T. N. (1970) The period of susceptibility to the physiological effects of unilateral eye closure in kittens, J Physiol, 206, 419-436.

[9] Whitton, J. P, Polley, D. B. (2011) Evaluating the perceptual and pathophysiological consequences of auditory deprivation in early postnatal life: a comparison of basic and clinical studies. J Assoc Res Otolaryngol, 12, 535-47.

[10] Weder, N., Kaufman, J. (2013) Critical Periods Revisited: Implications for Intervention with Traumatized Children, J Am Acad Child Adolesc Psychiatry, 50, 1087-1089.

[11] Hensch, T. K., (2005). Critical period plasticity in local cortical circuits, Nature Reviews Neuroscience, 6, 877-888.

[12] Pynoos, R. S., Steinberg, A. M., & Wraith, R. (1995). A developmental model of childhood traumatic stress. Developmental psychopathology, 2, 72-95.

[13] Luecken, L. J., Lemery, K. S. (2004). Early caregiving and physiological stress responses, Clinical Psychology Review, 24, 171-191.

[14] Cassidy, J. (1994) Emotion regulation: influences of attachment relationships, Monogr Soc Res Child Dev, 59, 228-49.

[15] Bowlby, J. (1982). Attachment and loss: retrospect and prospect. American journal of Orthopsychiatry, 52(4), 664.

[16] De Bellis, M. D. (2002) Developmental traumatology: a contributory mechanism for alcohol and substance use disorders, Psychoneuroendocrinology, 27, 155-170.

[17] Welberg, L. A., Seckl, J. R. (2001) Prenatal stress, glucocorticoids and the programming of the brain, J Neuroendocrinol., 13, 113-28.

[18] Vasquez, D. M. (1997) Stress and the Developing Limbic-Hypothalamic-Pituitary-Adrenal Axis, Psychoneuroendocrinology, 23, 663-700.

[19] Conrad, C. D., LeDoux, J. E., Magarinos, A. M., McEwen, B. S. (1999) Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy, Behav Neurosci, 113, 902-13.

[20] Sackett, G., et al. (1973). Adrenocortical and behavioral reactions by differentially raised rhesus monkeys. Physiological Psychology, 1, 209-212.

[21] Graham, Y. P., Heim, C., Goodman, S. H., Miller, A. H., Nemeroff, C. B. (1999) The effects of neonatal stress on brain development: implications for psychopathy, Dev Psychopathol, 11, 545-65.

[22] Heim, C., Owens, M. J., Plotsky, P. M., Nemeroff, C. B. (1997) The role of early adverse life events in the etiology of depression and post traumatic stress disorder. Focus on the corticotropin-releasing factor, Ann N Y Acad Sci, 821, 194-207.

[23] Ronald de Kloet, E. R., Rots, N. Y., Cools, A. R. (1996) Brain-corticosteroid hormone dialogue: slow and persistent, Cell Mol Neurobiol, 16, 345-56.

[24] Gunnar, M. R., Brodersen, L., Nachmias, M., Buss, K., Rigatuso (1996) Stress reactivity and attachment security, Dev Psychobiol, 29, 191-204.

[25] American Psychological Association. (n.d.). Apa Dictionary of Psychology. American Psychological Association. https://dictionary.apa.org/insecure-attachment

[26] American Psychological Association. (n.d.). Apa Dictionary of Psychology. American Psychological Association. https://dictionary.apa.org/secure-attachment

[27] Heim, C., Ehlert, U., Hellhammer, D. H. (2000) The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders, Psychoneuroendocrinology, 25, 1-35.

[28] Smyke, A. T., Zeanah Jr, C. H., Fox, N. A., Nelson 3rd, C. A. (2009) A new model of foster care for young children: the Bucharest early intervention project, Child Adolesc Psychiatr Clin N Am, 18, 721-34.

[29] Smyke, A. T., Zeanah, C. H., Fox, N. A., Nelson, C. A., Guthrie, D. (2010) Placement in Foster Care Enhances Quality of Attachment Among Young Institutionalized Children, Child Dev, 81, 212-223.

[30] Corpechot, C., Robel, P., Axelson, M., Sjövall, J., Baulieu, E. E. (1981) Characterization and measurement of dehydroepiandrosterone sulfate in rat brain, Proc Natl Acad Sci U S A, 78, 4704-4707.