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The functioning of the hypothalamic–pituitary–adrenal (HPA) axis is implicated in the etiology and maintenance of depressive and posttraumatic stress disorder (PTSD) symptoms. However, different maltreatment experiences as well as the increased sensitivity of the HPA axis during puberty may alter associations between the HPA axis and mental health. To address these gaps, the current study examined the potential bidirectional associations between cortisol reactivity to a stressor, PTSD symptoms, and depressive symptoms among early adolescents across two time points, 1 year apart (n = 454; Mage = 10.98 at Time 1 and Mage = 12.11 at Time 2). Multiple-group path models tested the pathways between cortiol reactivity and mental health prior to and during puberty, for different types of maltreatment . Overall, the results showed that associations between cortisol output and symptoms of PTSD and depression were driven by those in the midst of puberty. Specifically, higher cortisol output at Time 1 was linked with higher levels of subsequent PTSD and depressive symptoms for neglected youth who had reached puberty. However, depressive symptoms predicted subsequent lower cortisol output for the physical abuse and emotional abuse groups. These findings demonstrate longitudinal links between cortisol, depressive symptoms, and PTSD symptoms among youth with different types of maltreatment histories and highlight the need to consider the reorganization of the stress system during puberty in order to advance our understanding of the HPA axis and mental health.
Testosterone (T) and cortisol (C) are steroid hormones that have been argued to play opposing roles in shaping physical and behavioral development in humans. While there is evidence linking T and C to different memory processes during adulthood, it remains unclear how the relative levels of T and C (TC ratio) may influence brain and behavioral development, whether they are influenced by sex of the child, and whether or not they occur as a result of stable changes in brain structure (organizational changes), as opposed to transient changes in brain function (activational changes). As such, we tested for associations among TC ratio, cortico-hippocampal structure, and standardized tests of executive, verbal, and visuo-spatial function in a longitudinal sample of typically developing 4–22-year-old children and adolescents. We found greater TC ratios to be associated with greater coordinated growth (i.e. covariance) between the hippocampus and cortical thickness in several areas primarily devoted to visual function. In addition, there was an age-related association between TC ratio and parieto-hippocampal covariance, as well as a sex-specific association between TC ratio and prefrontal-hippocampal covariance. Differences in brain structure related to TC ratio were in turn associated with lower verbal/executive function, as well as greater attention in tests of visuo-spatial abilities. These results support the notion that TC ratio may shift the balance between top-down (cortex to hippocampus) and bottom-up (hippocampus to cortex) processes, impairing more complex, cortical-based tasks and optimizing visuospatial tasks relying primarily on the hippocampus.
Adolescent risk for self-injurious thoughts and behaviors (STBs) involves disturbance across multiple systems (e.g., affective valence, arousal regulatory, cognitive and social processes). However, research integrating information across these systems is lacking. Utilizing a multiple-levels-of-analysis approach, this person-centered study identified psychobiological stress response profiles and linked them to cognitive processes, interpersonal behaviors, and STBs. At baseline, adolescent girls (N = 241, Mage = 14.68 years, Range = 12–17) at risk for STBs completed the Trier Social Stress Test (TSST), questionnaires, and STB interviews. Positive affect (PA), negative affect (NA), and salivary cortisol (SC) were assessed before and after the TSST. STBs were assessed again during 3, 6, and 9 month follow-up interviews. Multitrajectory modeling of girls’ PA, NA, and SC revealed four profiles, which were compared on cognitive and behavioral correlates as well as STB outcomes. Relative to normative, girls in the affective distress, hyperresponsive, and hyporesponsive subgroups were more likely to report negative cognitive style (all three groups) and excessive reassurance seeking (hyporesponsive only) at baseline, as well as nonsuicidal self-injury (all three groups) and suicidal ideation and attempt (hyporesponsive only) at follow-up. Girls’ close friendship characteristics moderated several profile–STB links. A synthesis of the findings is presented alongside implications for person-centered tailoring of intervention efforts.
Chaetodon striatus is a cosmopolitan seawater species present in aquaria all over the world and its extractivism is quite high. The lack of studies on the reproductive biology of C. striatus contributes to the difficulty in managing the species outside its natural habitat. Without knowledge of the mechanisms that control or affect gonadal changes, reproduction of C. striatus in captivity has become almost impossible, considering that the species is quite sensitive and the effect of captive conditions on its reproductive biology is unknown. Therefore, this study aimed to evaluate the effect on its reproductive biology of the animal’s confinement and possible alteration in structure of the ovaries. In C. striatus, after oocyte development, for animals confined in small spaces, maturing oocytes undergo atresia. During atresia, ovarian follicles were at different stages of degeneration, characterized by the progressive loss of the basement membrane and disorganization of the follicle complex. In the advanced stage of follicular atresia, there was total loss of the basement membrane, culminating in degradation of the follicle complex. In unconfined animals, oocyte development and maturation were not affected. Confinement also affected the cell structure of the germinal epithelium, which showed large numbers of apoptotic bodies. The difference in cortisol and glucose levels between the unconfined and confined groups was significant, which may have to do with the change found in the ovaries, such as extensive follicular atresia and loss of the basement membrane.
Stress during pregnancy has been widely studied and associated to different variables, usually with negative results for the health of the mother and the newborn, such as having a higher risk of suffering postpartum depression, premature birth, obstetrics complications or low birthweight, among others. However, there are not many lines of research that study the role that the sex of the baby plays on this specific stress and vice versa. Thus, the main objective was to analyse the relationship between the sex of the offspring and the stress of the mothers in the first trimester of pregnancy. In order to achieve this, 108 women had their biological stress measured (trough hair cortisol levels) and psychological stress evaluated (the Prenatal Distress Questionnaire (PSS), the Perceived Stress Scale (PDQ) and the Stress Vulnerability Inventory (IVE)). The results revealed significant differences in maternal hair cortisol levels in the first trimester based on the sex of the baby they had given birth to (t = −2.04; P < 0.05): the concentration of the hormone was higher if the baby was a girl (164.36:54.45-284.87 pg/mg) than if it was a boy (101.13:37.95-193.56 pg/mg). These findings show that the sex of the future baby could be conditioned, among many other variables, by the mother´s stress levels during conception and first weeks of pregnancy. Further research is needed in this area to support our findings.
Megan Gunnar's pubertal stress recalibration hypothesis was supported in a recent study of previously institutionalized (PI) youth such that increases in pubertal stage were associated with increases in cortisol stress reactivity. This work provides evidence that puberty may open up a window of recalibration for PI youth, resulting in a shift from a blunted to a more typical cortisol stress response. Using the same sample (N = 132), the current study aimed to elucidate whether increases in cortisol are associated with increases in adaptive functioning or whether they further underlie potential links to developmental psychopathology. Specifically, we examined the bidirectional associations between cortisol stress reactivity and both internalizing and externalizing symptoms across three timepoints during the pubertal period. Youth reported on their own internalizing symptoms and parents reported on youths’ externalizing symptoms. Cortisol reactivity was assessed during the Trier social stress test. Analyses revealed no associations between cortisol reactivity and externalizing symptoms across puberty for PI youth. However, longitudinal bidirectional associations did emerge for internalizing symptoms such that increases in cortisol reactivity predicted increases in internalizing symptoms and increases in internalizing symptoms predicted increases in cortisol reactivity. Findings suggest that recalibrating to more normative levels of cortisol reactivity may not always be associated with adaptive outcomes for PI youth.
Children who have been adopted internationally commonly experience institutional care and other forms of adversity prior to adoption that can alter the functioning of the hypothalamic–pituitary–adrenal (HPA) axis. In particular, internationally adopted children tend to have blunted diurnal declines compared to children raised in their birth families. The Attachment and Biobehavioral Catch-Up (ABC) intervention was developed to enhance young children's biological and behavioral regulation by promoting sensitive parenting. The current study used a randomized controlled trial to assess whether ABC improved the diurnal functioning of the HPA axis among 85 children who had been adopted internationally when they were between the ages of 4 and 33 months (M = 16.12). Prior to the intervention, there were no significant differences in diurnal cortisol production between children whose parents were randomly assigned to receive ABC and children whose parents were randomly assigned to receive a control intervention. After the intervention, children whose parents had received the ABC intervention exhibited steeper declines in cortisol levels throughout the day than children whose parents had received the control intervention. These results indicate that the ABC intervention is effective in enhancing a healthy pattern of diurnal HPA axis regulation for young children who have been adopted internationally.
We review evidence of racial discrimination as a critical and understudied form of adversity that has the potential to impact stress biology, particularly hypothalamic–pituitary–adrenal (HPA) axis activity. We highlight ethnic racial identity (ERI) as a positive regulatory influence on HPA axis activity, as indexed by levels of salivary cortisol. In past research by our group, Black individuals with high adolescent discrimination had low adult cortisol levels (hypocortisolism). Here, we present new analyses showing that ERI, measured prospectively from ages 12 through 32 in 112 Black and white individuals, is related to better-regulated cortisol levels in adulthood, particularly for Black participants. We also describe ongoing research that explores whether the promotion of ERI during adolescence can reduce ethnic–racial disparities in stress biology and in emotional health and academic outcomes.
Environmental adversity increases child susceptibility to disrupted developmental outcomes, but the mechanisms by which adversity can shape development remain unclear. A translational cross-species approach was used to examine stress-mediated pathways by which poverty-related adversity can influence infant social development. Findings from a longitudinal sample of low-income mother–infant dyads indicated that infant cortisol (CORT) on its own did not mediate relations between early-life scarcity-adversity exposure and later infant behavior in a mother-child interaction task. However, maternal CORT through infant CORT served as a mediating pathway, even when controlling for parenting behavior. Findings using a rodent “scarcity-adversity” model indicated that pharmacologically blocking pup corticosterone (CORT, rodent equivalent to cortisol) in the presence of a stressed mother causally prevented social transmission of scarcity-adversity effects on pup social behavior. Furthermore, pharmacologically increasing pup CORT without the mother present was not sufficient to disrupt pup social behavior. Integration of our cross-species results suggests that elevated infant CORT may be necessary, but without elevated caregiver CORT, may not be sufficient in mediating the effects of environmental adversity on development. These findings underscore the importance of considering infant stress physiology in relation to the broader social context, including caregiver stress physiology, in research and interventional efforts.
Understanding individual differences in neural responses to stressful environments is an important avenue of research throughout development. These differences may be especially critical during adolescence, which is characterized by opportunities for healthy development and increased susceptibility to the development of psychopathology. While the neural correlates of the psychosocial stress response have been investigated in adults, these links have not been explored during development. Using a new task, the Minnesota Imaging Stress Test in Children (MISTiC), differences in activation are found in fusiform gyrus, superior frontal gyrus, insula, and anterior cingulate cortex when comparing a stressful math task to a nonstressful math task. The MISTiC task successfully elicits cortisol responses in a similar proportion of adolescents as in behavioral studies while collecting brain imaging data. Cortisol responders and nonresponders did not differ in their perceived stress level or behavioral performance during the task despite differences in neuroendocrine function. Future research will be able to leverage the MISTiC task for many purposes, including probing associations between individual differences in stress responses with environmental conditions, personality differences, and the development of psychopathology.
Stress associated with caring for a mentally ill spouse can adversely affect the health status of caregivers and their children. Adding to the stress of caregiving is the stigma often placed against spouses and children of people with mental illness. Contrary to mental illness, many physical disorders such as cancer may be less stigmatized (expect pulmonary cancer). In this study, we measured externalized and internalized stigma, as well as psychological (depressive symptoms and stressful life events) and physiological (basal salivary cortisol levels) markers of stress in 115 spouses and 154 children of parents suffering from major depressive disorder, cancer, or no illness (control group). The results show that spouses and children from families with parental depression present significantly more externalized stigma than spouses and children from families with parental cancer or no illness, although we find no group differences on internalized stigma. The analysis did not show a significant group difference either for spouses or their children on depressive symptomatology, although spouses from the parental depression group reported greater work/family stress. Finally, we found that although for both spouses children the awakening cortisol response was greater on weekdays than on weekend days, salivary cortisol levels did not differ between groups. Bayes factor calculated on the null result for cortisol levels was greater than 100, providing strong evidence for the null hypothesis H0. Altogether, these results suggest an impact of stigma toward mental health disorder on psychological markers of stress but no impact of stigma on physiological markers of stress. We suggest that these results may be due to the characteristics of the families who participated in the present study.
Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested.
A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure.
The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; M = −0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; M = −275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms.
The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.
If performance goals (i.e., motivation to prove ability) increase children's vulnerability to depression (Dykman, 1998), why are they overlooked in the psychopathology literature? Evidence has relied on self-report or observational methods and has yet to articulate how this vulnerability unfolds across levels of analysis implicated in stress–depression linkages; for example, hypothalamic–pituitaryadrenal axis (HPA), sympathetic nervous system (SNS). Utilizing a multiple-levels-of-analysis approach (Cicchetti, 2010), this experimental study tested Dykman's goal orientation model of depression vulnerability in a community sample of preadolescents (N = 121, Mage = 10.60 years, Range = 9.08–12.00 years, 51.6% male). Self-reports of performance goals, attachment security, and subjective experience of internalizing difficulties were obtained in addition to objective behavioral (i.e., task persistence) and physiologic arousal (i.e., salivary cortisol, skin conductance level) responses to the Trier Social Stress Test (TSST) and two randomly assigned coping conditions: avoidance, distraction. Children with performance goals reported greater internalizing difficulties and exhibited more dysregulated TSST physiologic responses (i.e., HPA hyperreactivity, SNS protracted recovery), yet unexpectedly displayed greater TSST task persistence and more efficient physiologic recovery during avoidance relative to distraction. These associations were stronger and nonsignificant in the context of insecure and secure attachment, respectively. Findings illustrate a complex matrix of in-the-moment, integrative psychobiological relationships linking performance goals to depression vulnerability.
Welfare of dairy cows can be assessed using welfare assessment protocols consisting of resource, management and animal-based measures. Welfare Quality® Assessment Protocol is one of the best-known protocols, which depends almost entirely on animal-based measures. To gain more objective and rapid welfare assessment, new techniques have been developed to measure welfare of animals, such as hair cortisol concentration. As cortisol is released in response to stress, it has long been used as a biomarker of stress in animals. While the precise mechanism of cortisol incorporation into hair is unknown, hair cortisol concentration seems to be a marker of long-term systemic cortisol concentration. Hair cortisol is, therefore, a potential marker of chronic stress and is not likely to be affected by acute stress. Studies on cattle show connections between hair cortisol concentration and factors such as pregnancy, parity, diseases, ectoparasites, body condition score, environmental changes, stocking density and milk yield. Hair cortisol concentration appears to be affected by time of sampling, cow age and breed, UV radiation, season, body region of sampled hair and hair colour. Its concentration also depends on sampling and analytical methods. Hair cortisol is a promising non-invasive tool to evaluate welfare of dairy cows, however, more research is needed to determine the extent of effects on its concentration and the appropriate method of sampling and analysis. Correlations between Welfare Quality® Assessment Protocol scores and pooled hair cortisol concentrations have not yet been found, and more research is needed with larger sample size, a standardized protocol of hair sampling, processing and analysis. With proper attention to detail, hair cortisol levels in pooled hair samples might come to be used as a reliable indicator of dairy animal welfare.
Dysregulation in children's physiological stress systems is a key process linking early adversity to poor health and psychopathology. Thus, interventions that improve children's stress physiology may help prevent deleterious health outcomes. Reminiscing and Emotion Training (RET) is a brief relational intervention designed to improve maternal caregiving support by enhancing maltreating mothers’ capacity to reminisce with their young children. This study evaluated associations between maltreatment, intimate partner violence, and the RET intervention with changes in children's diurnal cortisol regulation across the 1 year following the intervention, and the extent to which improvements in maternal elaborative reminiscing differed between intervention groups and mediated change in children's physiological functioning. Participants were 237 children (aged 36 to 86 months) and their mothers. Results indicated that the RET intervention was associated with significant positive change in elaborative reminiscing, which was sustained over time. Mothers’ elaboration immediately after the intervention served as a mediator of RET's effects on improvements in children's diurnal cortisol regulation (steeper diurnal slopes) from baseline to 1 year following intervention. This suggests RET is effective in facilitating physiological regulation among maltreated children.
Maltreatment adversely impacts the development of children across a host of domains. One way in which maltreatment may exert its deleterious effects is by becoming embedded in the activity of neurophysiological systems that regulate metabolic function. This paper reviews the literature regarding the association between childhood maltreatment and the activity of three systems: the parasympathetic nervous system, the sympathetic nervous system, and the hypothalamic–pituitary–adrenal axis. A particular emphasis is placed on the extent to which the literature supports a common account of activity across these systems under conditions of homeostasis and stress. The paper concludes with an outline of directions for future research and the implications of the literature for policy and practice.
This study examined the link between two biological markers of stress vulnerability at 22–26 years of age and telomere length at 30–35 among extremely low birth weight (ELBW; <1000 g) survivors and normal birth weight (NBW; >2500 g) control participants. Sixteen ELBW and 22 NBW participants provided baseline afternoon salivary cortisol samples and resting frontal electroencephalogram (EEG) alpha asymmetry data at 22–26 years. Buccal cells were assayed for telomere length at 30–35 years. Analyses controlled for sex, postnatal steroid exposure, childhood socioeconomic status, time of cortisol sample collection, and body mass index at 22–26 years. Salivary cortisol and frontal asymmetry at age 22–26 independently predicted telomere length at age 30–35, such that relatively higher cortisol and greater relative right frontal asymmetry at rest predicted telomere shortening among NBW controls, but not among ELBW survivors. However, similar associations were not noted in ELBW survivors, suggesting that ELBW survivors may have different mechanisms of stress coping as a result of their early-life exposures. These findings offer preliminary evidence in support of the role of stress in the genesis of cellular senescence at least among those born at NBW, but that these links may differ in those born preterm.
Free cortisol was investigated in BPD patients and healthy controls. A positive association was found between cortisol and depression scores, while the number of PTSD symptoms was negatively correlated with cortisol release. These findings suggest that alterations in cortisol release in BPD are strongly associated with the severity of psychopathology.
Emotional processing and cortisol were investigated in non-depressed young adults whose mothers experienced PND. PND-exposed participants (n = 11) had higher waking salivary cortisol and slower performance on an emotional categorization task than controls (n = 15). This supports the hypothesis that early exposure to maternal depression is associated with characteristics reminiscent of vulnerability to depression.
The aim of this study was to identify possible peripheral biological markers (both lipidic and hormonal) which can be easily used for the early detection of parasuicidal behaviour and to propose a predictive biological model of such behaviour. A case-control analytical study was undertaken at least 3 months after attempted suicide. Study was made of 128 patients who presented at the University General Hospital of Oviedo (Spain) with signs of self-intoxication. Lipidic and hormonal profiles were measured under basal conditions and comparison was made with a control group of healthy volunteer donors obtained from the Oviedo General Hospital blood bank. A discriminant analysis was later made with the aim of establishing a predictive biological model. This included the following variables: cholesterol, HDL-C, LDL-C and cortisol. Sensitivity and specificity were 62.5% and 65.6%, respectively. Replication and improvement of this model, through other prospective studies, could lead to the use of serum cholesterol and cortisol levels as inexpensive and readily available markers of suicide risk.