Mitigating HPA axis dysregulation associated with placement changes in foster care

Maltreated foster children often exhibit alterations in diurnal hypothalamic-pituitary-adrenal (HPA) axis activity that are characterized by lower cortisol levels upon waking and smaller declines in morning-to-evening cortisol levels. Previous research has shown that this dysregulated pattern is associated with high caregiver stress levels over the course of foster care placements. In contrast, therapeutic interventions that emphasize consistent and responsive caregiving have been associated with more regulated cortisol rhythms. In this paper, two related issues were explored: whether placement changes (i.e., moving between foster homes or from a foster home to a permanent placement) were associated with more blunted daily cortisol rhythms and whether a caregiver-based intervention exerted a protective effect in this context. Because the intervention program has components specifically designed to prepare foster children for placement changes and to maintain consistent parenting techniques despite them, a prevention effect on HPA axis dysregulation during placement changes was hypothesized. The results of linear mixed modeling analyses showed that placement changes predicted dysregulation in cortisol rhythms in the regular foster care group but not in the intervention foster care group. These findings are discussed in terms of implications for child welfare policy and practice.     

The relation between early life adversity, cortisol awakening response and diurnal salivary cortisol levels in postpartum women

Early life adversity has been associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in both children and adults. However, in adulthood, most studies have focused on the effects of early adversity on HPA axis stress reactivity rather than the cortisol awakening response or diurnal cortisol profiles. The goal of this study was to examine the cumulative effects of early life adversity on the cortisol awakening response (CAR) and diurnal cortisol profiles in a sample of postpartum women. Ninety women between 2 and 6 months postpartum completed two retrospective reports assessing adverse early life experiences (maltreatment and consistency of care). Eighteen women reported having experienced both parental loss and some form of childhood maltreatment and 36 women reported having experienced one type of early life adversity, either parental loss or maltreatment. HPA axis function was assessed through salivary cortisol collections over two consecutive days for measurement of the cortisol awakening response (n=61) and diurnal cortisol rhythm (n=90). Women who reported experiencing adverse early life experiences exhibited a tendency towards higher levels of awakening cortisol compared to women who reported no adverse early life experiences (p=.07). These higher awakening cortisol levels were sustained throughout the morning in the groups who experienced early adversity, with all groups exhibiting the typical diurnal decline in the afternoon and evening (p<.05). Women reporting early adversity exhibited more heterogeneity in their diurnal cortisol levels across the two collection days (p<.01). Our findings suggest that in a community sample of postpartum women, early adversity is associated with current HPA axis function. These findings may have implications for the nature of mother-infant interactions.     

Diurnal cortisol after early institutional care—Age matters

Several studies have shown that young children who have experienced early caregiving adversity (e.g. previously institutionalization (PI)) exhibit flattened diurnal cortisol slopes; however, less is known about how these patterns might differ between children and adolescents, since the transition between childhood and adolescence is a time of purported plasticity in the hypothalamic-pituitary-adrenal (HPA) axis. PI youth experience a massive improvement in caregiving environment once adopted into families; therefore we anticipated that a developmental increase in HPA axis plasticity during adolescence might additionally allow for an enhanced enrichment effect by the adoptive family. In a cross-sectional sample of 197 youths (PI and Comparison; 4–15 years old) we observed age-related group differences in diurnal slope. First replicating previous findings, PI children exhibited flattened diurnal slope. This group difference, however, was not observed in adolescents. Moderation analyses showed that pubertal development, increased time with family, and early adoption contributed to the steeper diurnal cortisol slope in PI adolescents. These findings add support to existing theories positing that the transition between middle childhood and adolescence may mark an additional sensitive period for diurnal cortisol patterning, allowing PI youth to benefit from the enriched environment provided by adoptive parents during this period of development.     

Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior

Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behavior. Accordingly, the impact of IFN-alpha on diurnal secretion of hypothalamic-pituitary-adrenal (HPA) axis hormones was assessed in 33 patients eligible for treatment with IFN-alpha plus ribavirin for hepatitis C. In addition, the relationship between IFN-alpha-induced HPA axis changes and proinflammatory cytokines and behavior was examined. Plasma ACTH and cortisol as well as tumor necrosis factor (TNF)-alpha, interleukin-6 and their soluble receptors, were measured hourly between 0900 and 2100 hours at baseline and following approximately 12 weeks of either no treatment (n=13) or treatment with IFN-alpha/ribavirin (n=20). Plasma IFN-alpha was also measured at each visit. Depression and fatigue were assessed using the Montgomery-Asberg depression rating scale and the multidimensional fatigue inventory. Compared to no treatment, IFN-alpha/ribavirin administration was associated with significant flattening of the diurnal ACTH and cortisol slope and increased evening plasma ACTH and cortisol concentrations. Flattening of the cortisol slope and increases in evening cortisol were correlated with increases in depression (r=0.38, P<0.05 and r=0.36, P<0.05, respectively) and fatigue (r=0.43, P<0.05 and r=0.49, P<0.01, respectively). No relationship was found between immune and HPA axis measures, although increases in plasma IFN-alpha, TNF-alpha and soluble TNF-alpha receptor2 were independently correlated with behavioral endpoints. These data indicate that chronic exposure to innate immune cytokines may contribute to the altered diurnal HPA axis activity and behavior found in medically ill individuals. However, given the lack of correlation between HPA axis and immune measures, the mechanism by which chronic cytokine exposure influences HPA axis function remains to be determined.     

Examining cortisol rhythmicity and responsivity to stress in children with Tourette syndrome

BACKGROUND: Tourette syndrome (TS) is characterized by motor and vocal tics, which are often exacerbated by stress. The hypothalamic-pituitary-adrenocortical (HPA) axis, a major stress response system is thus of interest for understanding TS. METHODS: Diurnal cortisol rhythms were estimated in medication-free children 7-13 years with TS (N=20) and healthy age-matched controls (N=16). Salivary samples were collected on 3 consecutive days from the home. HPA responsivity was assessed by examining cortisol in response to a mock and real MRI scan. RESULTS: The results of diurnal rhythmicity revealed a trend showing marginally lower evening cortisol for the TS group. By contrast, the TS group had higher cortisol levels in response to the stressor. There were strong, negative correlations between evening cortisol and tic severity as well as diurnal cortisol and anxiety. CONCLUSIONS: The children with TS showed increased cortisol in response to the MRI environment, supporting a model of enhanced HPA responsivity. The lower evening cortisol may be the result of chronic daily stress. Alternatively, the negative associations between cortisol and reported anxiety and tics may reflect biologically based anxiolytic properties of tic expression. Taken together, the results clearly implicate involvement of the HPA axis in the neuropathology of TS.     

Moderate versus severe early life stress: associations with stress reactivity and regulation in 10-12-year-old children

Early life stress (ELS) is expected to increase reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis; however, several recent studies have shown diminished cortisol reactivity among adults and children with ELS exposure. The goal of this study was to examine cortisol activity in 10-12-year-old internationally adopted children to determine if moderate and severe ELS have different impacts on the HPA axis. Salivary cortisol and two measures of autonomic activity were collected in response to the Trier Social Stress Test for Children (TSST-C). Three groups reflecting moderate, severe, and little ELS were studied: early adopted children who came predominantly from foster care overseas (early adopted/foster care (EA/FC), n=44), later adopted children cared for predominantly in orphanages overseas (late adopted/post-institutionalized (LA/PI), n=42) and non-adopted (NA) children reared continuously by their middle- to upper-income parents in the United States (n=38). Diminished cortisol activity was noted for the EA/FC group (moderate ELS), while the LA/PI group (severe ELS) did not differ from the NA group. Overall, few children showed cortisol elevations to the TSST-C in any group. The presence/absence of severe growth delay at adoption proved to be a critical predictive factor in cortisol activity. Regardless of growth delay, however, LA/PI children exhibited higher sympathetic tone than did NA children. These results suggest that moderate ELS is associated with diminished cortisol activity; however, marked individual differences in cortisol activity among the LA/PI children suggest that child factors modify the impact of severe ELS. Lack of effects of severe ELS even for growth delayed children may reflect the restorative effects of adoption or the generally low responsiveness of this age group to the TSST-C.     

Latent state trait modeling of children's cortisol at two points of the diurnal cycle

One challenge in examining stable individual differences in basal activity of the HPA axis is controlling for internally or externally based situational factors that lead to day-to-day variation in ambulatory cortisol. Disturbed basal activity is of particular interest in studies with children, for whom a dysregulated HPA axis may play an etiologic role in emotional or health outcomes. The purpose of this study was to determine whether trait vs. situationally specific sources of variation can be identified at different points of the diurnal cycle in children and if so, whether state and trait components vary according to time of measurement. Early morning and late evening salivary cortisol was collected from 164 children aged 7 to 11 years. Samples were collected 30 min after wake-up and 30 min before bedtime on 3 weekdays. State, trait, and error components of cortisol levels were assessed using a latent state trait model. Possible influences of sampling day and outlier treatment on parameter estimates were examined. The results showed that a latent trait factor superimposed on state residuals and measurement error was identified for both early morning and late evening cortisol. Model fit was excellent and criteria for invariance tests were met. Trait factors accounted for 41% and 57% of the variance in morning and evening cortisol, respectively. These findings suggest cortisol attributed to trait factors can be identified and are of substantial magnitude at both the peak and nadir of the diurnal cycle. Latent state trait modeling is a potentially useful tool in understanding the role of stable individual differences in cortisol levels for development and health.     

With a little help from my friends: psychological, endocrine and health corollaries of social support in parental caregivers of children with autism or ADHD

Elevated psychological distress and concomitant dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated as one pathway that links the stress of caregiving with adverse health outcomes. This study assessed whether perceived social support might mitigate the psychological, endocrine and health consequences of caregiver stress in parents of children with autism and attention deficit hyperactivity disorder (ADHD). Parental caregivers completed measures of psychological distress, perceived availability of social support and physical health complaints. To capture important parameters of the basal diurnal cortisol pattern, caregivers collected salivary cortisol at waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Psychological distress and self reported physical health complaints were inversely related to scores on all support subscales: tangible, belonging, self esteem and appraisal. Results further revealed a significant, positive association between magnitude of the cortisol awakening response (CAR) and caregivers’ self esteem. As a buffer between the stress of caregiving and adverse physical health outcomes, social support acts to reduce stress appraisals and mitigate disturbances of the HPA axis. Moving forward, intervention programmes might seek to increase caregivers’ perceived availability of social resources.     

Co-occurring manic symptomatology influences HPA axis alterations in depression

Although dysfunctioning of the HPA axis is considered to be a core pathophysiological process in mood disorders, the evidence with regard to depression remains conflicting. This could partly be due to the large heterogeneity within mood disorders, since HPA axis abnormalities may also be associated with the extent of co-occurring manic symptomatology as is seen in bipolar disorder. In this study, patients with depressive disorder and bipolar spectrum disorders were studied with regard to their HPA axis functioning. In 304 healthy controls, 1134 patients with pure unipolar depressive disorder (UP), and 133 bipolar spectrum disorder patients (BD spectrum), cortisol was measured in 7 saliva samples to determine the 1 h cortisol awakening response (CAR), evening cortisol levels and cortisol suppression after a 0.5 mg dexamethasone suppression test. Both patient groups had overall higher CAR levels compared to controls, but only UP patients showed a higher increase over time in the CAR. A linear association was found between increasing bipolarity and cortisol diurnal slope: BD spectrum patients had a significantly higher diurnal slope than UP patients. Dexamethasone suppression did not differ between mood disorder diagnoses. The heterogeneity in HPA axis functioning in patients with depression can partially be explained by co-existing manic symptomatology, since an increase in the CAR appears to be more specific for pure depression whereas the presence of bipolarity is associated with an increase in the diurnal slope of cortisol.     

Exhaustion measured by the SF-36 vitality scale is associated with a flattened diurnal cortisol profile

The possible association between stress-related exhaustion and reduced activity in the hypothalamo-pituitary-adrenal (HPA) axis is increasingly in focus. The aim of the present study was to examine whether exhaustion measured in a non-patient population is associated with alterations in diurnal cortisol profile. The study population included 78 working individuals. The study group was dichotomised into exhausted and non-exhausted groups by means of the SF-36 vitality scale. Salivary cortisol was measured at three times during 1 workday: at awakening, 30min after awakening, and in the evening. The results showed that diurnal cortisol variation was significantly reduced in exhausted individuals. The difference in cortisol variation was mainly due to lowered morning cortisol in the exhausted group. Differences in cortisol levels at each sampling time or in mean diurnal output of cortisol were not statistically significant. The results would support the notion that exhaustion is associated with HPA axis hypoactivity as assessed by salivary cortisol. Furthermore, the SF-36 vitality provides a measure of exhaustion that may be useful in epidemiological studies in order to explore long-term health effects of stress-related exhaustion.