Developmental Change in Cortisol Reactivity Following Early Deprivation: Potential Links to Emotional Adjustment

Cortisol Stress Reactivity

Animal and human studies identify infancy as a sensitive period for shaping HPA axis regulation, including diurnal cortisol, the cortisol awakening response, and cortisol reactivity and recovery. Evidence suggests that cortisol reactivity may be especially sensitive to experiences of early deprivation (Howland et al., 2020). Cortisol reactivity reflects how strongly the HPA axis activates when a person encounters an acute stressor, typically measured as an increase from baseline to a poststressor peak. This response is driven by a coordinated HPA cascade that culminates in the release of glucocorticoids (cortisol in humans and corticosterone in rodents) that bind to mineralocorticoid and glucocorticoid receptors to mobilize energy, sharpen attention, and support coping. A negative feedback loop typically returns cortisol to baseline within 30 to 60 min after acute stress. However, prolonged or frequent stress can disrupt this regulatory process, leading to either blunted or elevated cortisol responses, both of which have been linked to negative health outcomes (McEwen & Wingfield, 2010).

Institutional Care and Blunted Cortisol Stress Reactivity During Childhood

Institutional care is marked by inconsistent adult responsiveness, increased exposure to neglect, and the absence of a stable caregiver who can coregulate and buffer stress. These conditions are thought to produce initially elevated cortisol levels that then activate biological mechanisms to reduce cortisol production (Miller et al., 2007). Dampening of the stress response may be adaptive in chronically stressful environments because it protects the developing child from the neurobiological costs of prolonged cortisol exposure (Lupien et al., 2009). However, calibration toward blunted cortisol reactivity may involve trade-offs that become particularly apparent when youth are removed from adverse early rearing conditions (Ellis & Boyce, 2008) because acute increases in cortisol support critical processes such as coordinating threat-related emotional responses and forming memories of stressful events (Sapolsky et al., 2000). Thus, dampened cortisol stress reactivity, although once adaptive, may also increase vulnerability to later emotional dysfunction.

Blunted cortisol reactivity has been documented across several samples of previously institutionalized children even years after removal from institutional care (DePasquale et al., 2020; Wade et al., 2024). Experimental evidence further supports a causal link between the duration of institutional care and blunted reactivity such that previously institutionalized children randomized to foster-care intervention in the Bucharest Early Intervention Project (BEIP) did not show a blunted cortisol response if they were removed from the institution before age 24 months (McLaughlin et al., 2015). Moreover, blunted cortisol reactivity is not limited to early institutional deprivation because it has also been observed following other types of maltreatment, abuse, and neglect (Bunea et al., 2017).

Blunted Cortisol Stress Reactivity and Emotional Problems During Childhood

Compared with peers raised in their birth families, previously institutionalized children show elevated emotional and behavioral problems (e.g., Juffer & Van Ijzendoorn, 2005; Merz & McCall, 2010). Whether blunted cortisol reactivity plays a causal role in previously institutionalized children’s emotional health, however, is not clear. In a longitudinal study assessing previously institutionalized children’s HPA functioning over the first 2 years after adoption, blunted cortisol reactivity served as a statistical mediator between early institutional care and teacher-reported attention and externalizing behaviors in kindergarten (Koss et al., 2016). In the BEIP sample, researchers found that blunted cortisol reactivity at age 12 statistically mediated the association between early institutionalization and later psychopathology (Wade et al., 2024). A comparable pattern was reported for adolescent boys who reported more early-life stress (Lee et al., 2024). Thus, blunted cortisol reactivity may be one mechanism underlying poorer emotional well-being in childhood, although it is certainly not the sole contributor because other biological and behavioral factors are integral to psychological health.

Because cortisol exerts its effects through mineralocorticoid and glucocorticoid receptors, the roles of these receptors in supporting healthy brain and emotional processes may help explain why blunted HPA stress responses are associated with poorer emotional functioning. Mineralocorticoid receptors support general neural processing and plasticity and are largely occupied at basal cortisol levels, whereas glucocorticoid receptors mediate neural activity in response to emotional challenge or threat and become more heavily occupied during periods of stress. Lower cortisol production, as observed in blunted HPA stress responses following adverse early rearing, may therefore result in reduced glucocorticoid receptor activation during environmental challenge, potentially limiting adaptive neural and physiological responses necessary for active coping. Indeed, reduced glucocorticoid receptor occupancy is associated with poorer cognitive performance (Herbert et al., 2006), and similar mechanisms may underlie emotional difficulties given the high concentration of mineralocorticoid and glucocorticoid receptors in emotion-related brain regions (McEwen & Morrison, 2013).

Puberty and Recalibration of Cortisol Stress Reactivity

How long, and for whom, cortisol reactivity remains blunted after early deprived rearing is unknown. Evidence suggests that the hormonal and biological changes of puberty may open a second sensitive period of plasticity during which the HPA stress response can be recalibrated to align with current environmental conditions. If the environment remains harsh, recalibration of the HPA axis is unlikely because the stress response is already down-regulated to cope with chronic stress at the adrenal level. However, if environmental conditions improve, recalibration during puberty would involve adjusting HPA stress responding to align with the less stressful context. Research on rodents shows that rats exposed to enriched environments after early chronic stress exhibit HPA stress responses similar to rats without early adversity (Francis et al., 2002; Romeo, 2018). Conversely, when infancy is benign, but puberty involves intense stress, HPA recalibration occurs to match the harsh environment, an effect not observed if the later stress occurs in adulthood (Romeo, 2018).

Gunnar and colleagues were the first to investigate whether puberty allows for a recalibration of cortisol reactivity in humans. They found that prepubertal previously institutionalized children showed significantly blunted cortisol reactivity during a social evaluative stressor. However, as youth progressed through pubertal stages, cortisol reactivity increased, and, by late puberty, previously institutionalized youth’s cortisol reactivity to psychosocial stress was not statistically different from that of youth raised in birth families (Gunnar et al., 2019). Notably, youth raised in their birth families showed no significant pubertal change in cortisol reactivity. This was as hypothesized because children reared in birth families were living in comparable environments in infancy and during puberty. Similar findings have been reported in children experiencing prolonged parent-child separation, for whom blunted cortisol reactivity normalized after reunion during the pubertal transition (Zhang et al., 2021). Together, these studies provide compelling evidence that HPA axis stress reactivity can recalibrate during puberty when environmental conditions differ from those experienced in early childhood. It remains unclear whether the increases in cortisol reactivity that occur during pubertal recalibration contribute to improvements in emotional health.

Recalibration of Cortisol Stress Reactivity and Pubertal Emotional Adjustment

If cortisol reactivity supports adaptive emotional functioning, pubertal recalibration to typical levels in previously institutionalized youth may result in postpubertal mental health similar to children raised in birth families. However, psychopathology increases with puberty more for previously institutionalized than family-reared youth (Perry, DePasquale, et al., 2022; Wade et al., 2024). Associations between pubertal increases in cortisol reactivity and previously institutionalized youth’s emotional health symptoms have been examined to better understand this phenomenon. Pubertal increases in HPA cortisol reactivity in previously institutionalized youth were unexpectedly accompanied by both greater parent-reported internalizing behaviors (Perry et al., 2020) and observed anxiety (Perry, DePasquale, et al., 2022). Notably, these associations persisted after accounting for stability in internalizing symptoms over time. Similar patterns were not observed in family-reared peers, suggesting that the increases cannot be explained by normative adolescent psychopathology. Increases in cortisol reactivity were not associated with externalizing behavior. To explore whether previously institutionalized youth require additional time after puberty for recalibrated cortisol reactivity to translate into improvements in emotional health, participants were recontacted approximately 4 years later for a follow-up mental-health assessment. The effects were not transient; previously institutionalized youth who showed pubertal increases in cortisol continued to exhibit higher levels of both internalizing and externalizing symptoms compared with youth raised in their birth families (Perry, Donzella, & Gunnar, 2022). It is important to acknowledge, however, that pubertal increases in cortisol reactivity were not associated with clinical levels of distress. Less than 10% of previously institutionalized youth scored in the clinical range for internalizing or externalizing symptoms on the MacArthur Health and Behavior Questionnaire (Lemery-Chalfant et al., 2007). Nonetheless, it is still unclear why HPA recalibration toward normative cortisol reactivity would be associated with greater emotional problems in previously institutionalized youth.

The specific pathways remain speculative because animal models are needed to clarify the mechanisms. After years of blunted responding, pubertal increases in cortisol reactivity may have neurobiological consequences for fear- and emotion-regulation circuitry (McLaughlin et al., 2014). The hippocampus, amygdala, and prefrontal cortex, regions rich in glucocorticoid receptors, are particularly sensitive to stress hormones (McEwen & Morrison, 2013). Animal models indicate that heightened HPA activity strengthens synaptic connections in the amygdala while weakening those in the prefrontal cortex and hippocampus, disrupting fear regulation (McEwen & Morrison, 2013). Thus, even if systemic cortisol levels are comparable in previously institutionalized and family-reared youth, pubertal increases in cortisol may be interpreted as heightened activation in the brain of a previously institutionalized child, potentially producing differential neural effects linked to psychopathology. Maternally deprived rats have been shown to have elevated corticotropin-releasing hormone and greater helplessness compared with typically reared rats despite similar systemic corticosterone levels (Plotsky & Meaney, 1993), consistent with this possibility. Furthermore, there is evidence that the early deprivation of maternal stimulation in rodents alters the ratio of mineralocorticoid to glucocorticoid receptors in the brain, thus resulting in altered patterns of response to the same increases in glucocorticoid levels (de Kloet et al., 2000).

Cortisol Reactivity and Emotional Adjustment in Young Adulthood

Internalizing symptoms are shown to persist into late adolescence and early adulthood for previously institutionalized individuals (Wade et al., 2024), with some evidence suggesting a marked increase over time (Sonuga-Barke et al., 2017). It remains unclear whether the typical levels of cortisol reactivity observed during pubertal recalibration persist into adulthood. No studies to date have examined cortisol reactivity from middle childhood through adulthood in either typical or early-adversity populations, leaving its long-term impact on emotional health unclear.

If the cortisol reactivity of previously institutionalized youth recalibrates during puberty and levels remain within the typical range in adulthood, positive associations between cortisol reactivity and mental-health symptoms may reflect differing neurobiological effects of early deprivation (McLaughlin et al., 2014). A blunted stress response could also reemerge in early adulthood, particularly if pubertal increases in cortisol contribute to unmanaged emotional symptoms that themselves act as chronic stressors. Prior work has demonstrated bidirectional effects, with increases in internalizing behaviors predicting subsequent rises in cortisol reactivity, suggesting that ongoing mental-health challenges may function as stressors even when other adversities subside (Perry, DePasquale, et al., 2022).

Alternatively, cortisol reactivity may continue to rise to abnormally high levels after puberty if years of hypofunctioning leave the negative feedback system underdeveloped and unable to regulate pubertal cortisol surges. Earlier pubertal stages are associated with blunted cortisol awakening responses among youth with higher early adversity, whereas later stages show atypically heightened responses (King et al., 2017), consistent with this possibility.

Although the typical trajectory is unknown, a postpubertal return to a blunted state or a shift toward cortisol hyperreactivity may carry negative implications for young adult mental health given the U-shaped relation between glucocorticoids and adaptive behavior (Herbert et al., 2006) and links between both hypo- and hypercortisolism and greater psychological and behavioral problems (Lopez-Duran et al., 2009; Ouellet-Morin et al., 2011; Wade et al., 2024). This underscores the importance of longitudinal research to clarify the developmental trajectories of cortisol reactivity and their interactions with neurobiological and psychosocial factors in shaping young adult emotional functioning.

Conclusions

Research with samples from previously institutionalized children offers a unique opportunity to clarify how early adverse rearing and deprivation shape the developing stress response system, raising key questions about how the timing and severity of early adverse care contribute to varying patterns in cortisol reactivity. Although cortisol is not the primary driver of emotion, substantial evidence links patterns of cortisol reactivity to emotional behavior across development in both previously institutionalized children and children exposed to other forms of adversity. This convergence suggests that developmental variation in cortisol stress reactivity over time may be one key mechanism through which early experiences exert long-term effects on emotional development. Future research should chart developmental patterns of cortisol reactivity from early childhood through adulthood among at-risk and typically developing children to determine whether cortisol reactivity stabilizes, increases, or returns to a blunted state postpuberty. Doing so may provide valuable insight into the etiology of emotional health in adults with histories of adverse care. In addition, research is needed to examine how ongoing stressors, such as discrimination in transracially adopted previously institutionalized youth, and factors such as genetics, sex, emotional support, and environmental resources shape cortisol reactivity trajectories and potentially amplify or buffer the influence of early adversity on adult psychological well-being.

Recommended Reading

Gunnar, M. R., DePasquale, C. E., Reid, B. M., Donzella, B., & Miller, B. S. (2019). (See References). Demonstrates evidence of HPA axis recalibration in a sample of previously institutionalized youth across the pubertal period.

Koss, K. J., & Gunnar, M. R. (2018). Annual Research Review: Early adversity, the hypothalamic–pituitary–adrenocortical axis, and child psychopathology. Journal of Child Psychology and Psychiatry, 59(4), 327–346. https://doi.org/10.1111/jcpp.12784. Describes the role of the HPA axis as a mediating mechanism between various forms of childhood adversity and psychopathology.

Perry, N. B., & Gunnar, M. R. (2019). Early deprivation and children’s emotional development: A developmental perspective. In V. LoBue, K. Pérez-Edgar, & K. A. Buss (Eds.), Handbook of emotional development (pp. 787–811). Springer. https://doi.org/10.1007/978-3-030-17332-6_29. Uses a developmental perspective to address how early neglect and deprivation may impact biobehavioral systems underlying emotional functioning.

Sonuga-Barke, E. J. S., Kennedy, M., Kumsta, R., Knights, N., Golm, D., Rutter, M., Maughan, B., Schlotz, W., & Kreppner, J. (2017). (See References). Assesses psychopathology symptoms from childhood to adulthood in English and Romanian adoptees, separating groups by age at adoption to isolate the duration of deprivation.

Wade, M., Parsons, J., Humphreys, K. L., McLaughlin, K. A., Sheridan, M. A., Zeanah, C. H., Nelson, C. A., & Fox, N. A. (2022). The Bucharest Early Intervention Project: Adolescent mental health and adaptation following early deprivation. Child Development Perspectives, 16(3), 157–164. Details the association between early deprivation and mental health during adolescence, highlighting the underpinning mechanisms across social-emotional, cognitive, stress, and neurobiological domains.