Impact of maternal trauma-related psychopathology and life stress on HPA axis stress response.

To understand and curb intergenerational transmission of stress-related disorder, it is important to identify how trauma-related psychopathology in mothers impacts their psychophysiological stress regulation, particularly in the context of parenting their infants. In this study we investigated associations between mothers' trauma-related psychopathology and life stress and HPA axis response to a personally relevant stressor (infant separation stress) in a non-clinical sample followed longitudinally postpartum. A community sample of low-income mothers (n = 73) and their infants completed laboratory sessions at 3, 6, 12, and 18 months postnatal, and salivary cortisol samples collected before and after dyadic stress tasks at the latter three sessions. These tasks were used to assess HPA function. A three-level hierarchical linear model of repeated cortisol measures nested within sessions within mother-infant dyads did not reveal significant main effects of trauma-related psychopathology on maternal cortisol response, but there was evidence that both a clinical interviewer-rated diagnosis of PTSD and ongoing self-reported trauma symptoms blunted effects of life events on cortisol reactivity. Region of significance analyses indicated that current life stress predicted more pronounced cortisol reactivity only among mothers without trauma-related psychopathology; for those with trauma-related psychopathology, life stress did not relate to cortisol response. Effects held when controlling for childhood trauma and previous (prenatal) maternal distress symptoms, suggesting they did not reflect ongoing impacts of past trauma exposure and/or psychopathology. Blunting effects of trauma-related psychopathology on maternal life stress responsiveness may help clarify how stress sensitivities and mental health are transmitted from parent to child.

Disentangling levels of mother-infant neuroendocrine attunement and longitudinal relations with maternal risk and protective factors.

Scientific understanding of mother-infant HPA axis attunement has been limited by discrepant methods for assessing attunement that often conflate different levels of association. We sought to refine the conceptualization of attunement by investigating whether mother-infant cortisol attunement exists as coupling of response trajectories within an acute stress episode, separate from shared developmental patterns and/or overall dyadic similarity in cortisol levels, and whether the degree of attunement depends on within- or between-dyad differences in maternal risk and protective factors. We examined these questions using a longitudinal study with mother/infant salivary cortisol during dyadic stressors at 6, 12, and 18 months postnatal. A three-level hierarchical linear model showed that sample-wide associations between mother and infant cortisol were not significant at any level, suggesting normative lack of attunement; however, there was significant variability in degree of attunement across dyads. Concurrent levels of family resources and social support satisfaction predicted lower mother-infant cortisol attunement within the session, and overall (mean) parenting stress predicted the opposite. Follow-up analyses showed this was typically due to an increase in infants' (but not their mothers') within-session cortisol response slopes with increasing support and decreasing stress. Implications for the role of mother-infant cortisol attunement in intergenerational stress transmission are discussed.

Maternal stress and social support prospectively predict infant inflammation.

Maternal stress has been suggested to be a risk factor for offspring health, while social support has been shown to be a protective factor for offspring functioning. Currently, research has yet to investigate how both of these factors may relate to infant inflammatory processes and associated biological aging in the first years of life. In 48 mother-infant dyads, we investigated whether maternal parenting stress and social support when infants were 12 and 18 months of age were cross-sectionally associated with infant salivary C-reactive protein (sCRP) during these times. In addition, we investigated whether parenting stress and social support were prospectively associated with later sCRP and changes in sCRP from 12 to 18 months of age, as well as whether those changes in sCRP were associated with subsequent infant salivary telomere length (sTL), a marker of biological aging. Analyses revealed that while there were no cross-sectional associations between maternal factors and infant sCRP, maternal parenting stress and social support when infants were 12 months of age predicted infant sCRP at 18 months of age. Further, maternal social support predicted changes in infant sCRP from 12 to 18 months of age. We observed a null association between infant sCRP and sTL. Implications for the ways that maternal mental health and social support may impact biological mechanisms related to disease processes in infants are discussed.

The quality of early infant-caregiver relational attachment and longitudinal changes in infant inflammation across 6 months.

The quality of early caregiver-infant relationships has powerful implications for health trajectories across the lifespan, including associations with adult inflammation. However, because relatively few studies have examined this association during infancy, it remains unclear when this impact occurs and whether it is associated with longitudinal changes in salivary concentrations of inflammation across infancy. In 45 infants, we investigated whether the quality of infant-caregiver attachment (secure vs. insecure) was associated not only with levels of salivary C-reactive protein (sCRP) cross-sectionally, but also with changes in sCRP across 6 months. Interestingly, while there were no cross-sectional associations between infant-caregiver attachment and inflammation at 12 months of age, infant-caregiver attachment security predicted lower levels of sCRP 6 months later. In addition, attachment security predicted decreasing levels of sCRP from 12 months to 18 months of age. Implications for understanding the influence of the quality of early relationships on biological mechanisms related to disease are discussed.

Perceived Discrimination, Racial Identity, and Multisystem Stress Response to Social Evaluative Threat Among African American Men and Women.

OBJECTIVE: Understanding individual differences in the psychobiology of the stress response is critical to grasping how psychosocial factors contribute to racial and ethnic health disparities. However, the ways in which environmentally sensitive biological systems coordinate in response to acute stress is not well understood. We used a social-evaluative stress task to investigate coordination among the autonomic nervous system, hypothalamic-pituitary-adrenal axis, and immune/inflammatory system in a community sample of 85 healthy African American men and women. METHODS: Six saliva samples, 2 at each of baseline, event, and recovery phases of the stressor task, were assayed for cortisol, dehydroepiandrosterone-sulfate, salivary alpha-amylase, and salivary C-reactive protein. Individual differences in perceived discrimination and racial identity were also measured. RESULTS: Factor analysis demonstrated that stress systems were largely dissociated before stressor exposure but became aligned during event and recovery phases into functional biological stress responses (factor loadings ≥ .58). Coordinated responses were related to interactions of perceived discrimination and racial identity: when racial identity was strong, highly perceived discrimination was associated with low hypothalamic-pituitary-adrenal axis activity at baseline (B's = .68-.72, p < .001), low stress mobilization during the task (B's = .46-.62, p < .049), and a robust inflammatory response (salivary C-reactive protein) during recovery (B's = .72-.94, p < .002). CONCLUSION: Culturally relevant social perceptions may be linked to a specific pattern of changing alignment in biological components of the stress response. Better understanding these links may significantly advance understanding of stress-related illnesses and disparities.

Mindfulness during romantic conflict moderates the impact of negative partner behaviors on cortisol responses.

This study was designed to test whether romantic partners' mindfulness-present moment, nonjudgmental awareness-during a conflict discussion could buffer the effects of negative partner behaviors on neuroendocrine stress responses. Heterosexual couples (n=88 dyads) provided 5 saliva samples for cortisol assay during a laboratory session involving a conflict discussion task. Conflict behaviors were coded by outside observers using the System for Coding Interactions in Dyads, and partners rated their mindfulness during the task using the Toronto Mindfulness Scale. Interactions tested using multilevel modeling revealed that participants with higher levels of mindfulness during the conflict showed either quicker cortisol recovery or an absence of slowed recovery in the presence of more negative partner behaviors. Whereas the attitudinal component of mindfulness (curiosity) moderated effects of negative partner engagement in the conflict (i.e., attempts to control, coerciveness, negativity and conflict), the attentional component of mindfulness (decentering) moderated the effect of partner disengagement (i.e., withdrawal). These findings lend support to the idea that mindfulness during a stressful interaction can mitigate the physiological impacts of negative behaviors.

Understanding the unfolding of stress regulation in infants.

Early identification of problems with psychosocial stress regulation is important for supporting mental and physical health. However, we currently lack knowledge about when reliable individual differences in stress-responsive physiology emerge and which aspects of maternal behavior determine the unfolding of infants' stress responses. Knowledge of these processes is further limited by analytic approaches that do not account for multiple levels of within- and between-family effects. In a low-risk sample (n = 100 dyads), we observed infant cortisol and mother/infant behavior during regular play and stress sessions longitudinally from age 1 to 3, and used a three-level model to separately examine variability in infant cortisol trajectories within sessions, across years, and across infants. Stable individual differences in hypothalamus-pituitary-adrenal axis regulation were observed in the first 3 years of life. Infants of less sensitive and more intrusive mothers manifested stress sensitization, that is, elevated cortisol levels during and following stress exposure, a profile related to behavioral distress. These findings have important practical implications, suggesting that children at risk for long-term stress dysregulation may be identified in the earliest years of life.

Combined Influences of Genes, Prenatal Environment, Cortisol, and Parenting on the Development of Children's Internalizing Versus Externalizing Problems.

Research suggests that genetic, prenatal, endocrine, and parenting influences across development individually contribute to internalizing and externalizing problems in children. The present study tests the combined contributions of genetic risk for psychopathology, prenatal environments (maternal drug use and internalizing symptoms), child cortisol at age 4.5 years, and overreactive parenting influences across childhood on 6-year-old children's internalizing and externalizing problems. We used data from an adoption design that included 361 domestically adopted children and their biological and adopted parents prospectively followed from birth. Only parenting influences contributed (independently) to externalizing problems. However, genetic influences were indirectly associated with internalizing problems (through increased prenatal risk and subsequent morning cortisol), and parenting factors were both directly and indirectly associated with internalizing problems (through morning cortisol). Results suggest that prenatal maternal drug use/symptoms and children's morning cortisol levels are mechanisms of genetic and environmental influences on internalizing problems, but not externalizing problems, in childhood.

HPA stability for children in foster care: mental health implications and moderation by early intervention.

Research on stress-sensitive biological systems has typically focused on activation at one time, yet recent theories emphasize dynamic, context-specific adaptation. This study tested hypothesized calibration of one such system by examining both mean levels and longitudinal stability of daily cortisol--reflecting hypothalamic-pituitary-adrenal axis activation--in children exposed to high-risk versus lower-risk caregiving contexts. Context-specific effects of longitudinal cortisol profiles were addressed via relations with child psychiatric symptoms. Children from regular foster care, foster children participating in a family-based intervention, and community comparison children (n = 96 total) collected saliva samples for cortisol assay at 29 timepoints across 6+ years. High-risk (regular foster care) children showed lower and more variable cortisol levels than their lower-risk (treatment foster care, community comparison) counterparts. For the high-risk children only, higher and more stable cortisol related to elevated anxiety symptoms. Implications for contextual calibration of stress systems and family intervention mechanisms are discussed.

Salivary nerve growth factor reactivity to acute psychosocial stress: a new frontier for stress research.

OBJECTIVE: Neurotrophins such as nerve growth factor (NGF) may represent a stress-responsive system complementing the better known neuroendocrine (hypothalamic-pituitary-adrenal axis) and autonomic nervous system, but there is little evidence for NGF response to acute stress in humans because noninvasive measures have not been available. We investigated salivary NGF (sNGF) in 40 healthy young adults confronting a romantic conflict stressor. METHODS: Five saliva samples-two collected before and three after the conflict-were assayed for sNGF, cortisol (hypothalamic-pituitary-adrenal marker), and α-amylase (sAA; ANS marker). In addition, a control group (n = 20) gave saliva samples at the same time intervals to determine whether sNGF changes were specific to the conflict stressor. RESULTS: sNGF showed significant reactivity from entry to the first poststress sample among study participants (ß = .13, p = .001), with nonsignificant change across poststress samples. Control participants showed no change in sNGF across the same period. Within-person changes in sNGF were generally aligned with both cortisol (ß = .17, p = .003) and sAA (ß = .17, p = .021) responses. Preconflict negative emotion predicted lower sNGF reactivity (ß = -.08, p = .009) and less alignment with sAA (ß = -.09, p = .040), whereas positive emotion predicted less alignment with cortisol (ß = -.10, p = .019). CONCLUSIONS: This study is the first to document sNGF as a marker that responds to stress in humans.

Effects of parental depressive symptoms on child adjustment moderated by hypothalamic pituitary adrenal activity: within- and between-family risk.

Child hypothalamic pituitary adrenal (HPA) activity was investigated as a moderator of parental depressive symptom effects on child behavior in an adoption sample (n = 210 families). Adoptive parents' depressive symptoms and child internalizing and externalizing were assessed at 18, 27, and 54 months, and child morning and evening HPA activity measured through salivary cortisol at 54 months. Children's daily cortisol levels and day-to-day variability were tested as moderators of longitudinal associations between parent and child symptoms at within- and between-family levels. Mothers' symptoms related directly to child internalizing, but child evening cortisol moderated effects of fathers' symptoms on internalizing, and of both parents' symptoms on externalizing. Different paths of within-family risk dynamics versus between-family risk synergy were found for internalizing versus externalizing outcomes.

Gender discrimination and women's HPA activation to psychosocial stress during the postnatal period.

Stress due to discrimination may contribute to physiological dysregulation and health risk during the postnatal period. This study examined longitudinal associations between gender discrimination and women's cortisol responses to subsequent stress. Mothers (N = 79) reported gender discrimination and completed mother-infant stress tasks with saliva sampling for cortisol at 6, 12, and 18 months postnatal. Multilevel modeling results indicated more overall gender discrimination was associated with higher cortisol. Changes in gender discrimination were not associated with cortisol over time. Gender discrimination may be a factor in women's postnatal stress and associated health risk via the sensitization of physiological stress responses.

Risky shifts: how the timing and course of mothers' depressive symptoms across the perinatal period shape their own and infant's stress response profiles.

We investigated the effects of timing and the course of maternal perinatal depressive symptoms on mother-infant hypothalamic-pituitary-adrenal (HPA) response profiles during an attachment stressor, as well as on within-dyad synchrony of stress profiles: coordination of HPA and sympathetic nervous system and infant-mother HPA attunement. Mothers (n = 86) completed the Center for Epidemiological Studies Depression Scale during pregnancy (Time 1 [T1]) and at 5 months (T2) and 18 months (T3) postnatal. At T3 mother-infant dyads completed the Strange Situation, and four saliva samples collected from both mothers and infants were assayed for cortisol and α-amylase. Hierarchical linear modeling was used to predict mother-infant cortisol response trajectories and within-dyad synchronies by main and interactive effects of T1-T3 Center for Epidemiological Studies Depression Scale scores. Main effects of earlier (T1, T2) depressive symptoms predicted mothers' cortisol trajectories and coordination, and interactions of T1 with postnatal (T2 and T3) symptoms predicted infants' cortisol trajectories, coordination, and attunement. Decomposition of interactions revealed more marked effects on infant cortisol trajectories when the mother shifted from higher to lower depressive symptoms (or vice versa) across the perinatal period. Shifts from lower to higher symptoms also predicted inverse coordination of cortisol with salivary α-amylase and greater attunement of infant with mother cortisol. Implications for the development and transmission of stress dysregulation are discussed.

Childhood abuse predicts affective symptoms via HPA reactivity during mother-infant stress.

Despite extensive literature positing the hypothalamic-pituitary-adrenal (HPA) axis as a mechanism in the association between early childhood maltreatment and later adult psychopathology, empirical support for this full pathway is lacking. We tested indirect effects of childhood maltreatment on women's later affective symptomatology via HPA axis responding to a stressor involving their own infant. Women (n = 47) in a larger longitudinal study were assessed following the birth of their infant from 3 to 18 months postnatal. They reported childhood maltreatment history at 3 months and participated in a dyadic stress task with their infant at 12 months, at which time four salivary cortisol samples were collected to assess HPA response. Depression and anxiety symptoms at 18 months (controlling for symptom levels reported at 12 months) served as the primary outcome. Multilevel modeling was used to estimate both levels and dynamics of women's cortisol response trajectories. Tests of indirect effects revealed a significant effect of total Childhood Trauma Questionnaire (CTQ) scores on anxiety symptoms and a marginally significant effect on depression symptoms. Follow-up analyses with CTQ subscales revealed significant indirect effects of emotional and physical abuse on women's ongoing anxiety symptoms via more pronounced cortisol reactivity curves during the mother-infant stressor. We discuss methodological choices that may have allowed these effects to be detected in the present study and implications for stress-related risk and intervention.

Mindful parenting predicts mothers' and infants' hypothalamic-pituitary-adrenal activity during a dyadic stressor.

Mindfulness in the parenting relationship has been proposed to help both parents and children better regulate stress, though this has not yet been shown at the physiological level. In this study, we tested relations between maternal mindfulness in parenting and both mothers' and their infants' hypothalamic-pituitary-adrenal (HPA) axis activity during a dyadic stressor 3 months later. Participants were 73 mother-infant dyads from a larger longitudinal study. At 3 months postpartum, mothers completed self-report measures of general dispositional mindfulness and parenting-specific mindfulness, as well as stressful life events. At 6 months postpartum, mother-infant dyads completed the Still Face task. Four saliva samples were collected from each dyad member for cortisol assay to index the HPA axis response. Hierarchical linear modeling of cortisol trajectories revealed a main effect of maternal parenting-specific mindfulness (mindful parenting), but not general dispositional mindfulness, on mothers' cortisol; mothers with higher mindful parenting showed steeper cortisol recovery slopes. In addition, maternal mindful parenting moderated the effect of life stress on later mother and infant cortisol. In the context of high life stress, maternal mindful parenting predicted lower infant cortisol levels, but more extended maternal cortisol elevations. Implications for a biobehavioral model of mindful parenting are discussed. (PsycINFO Database Record

Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect.

Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

Depression and anxiety predict sex-specific cortisol responses to interpersonal stress.

Clinical theories posit interpersonal stress as an important factor in the emergence and exacerbation of depression and anxiety, while neuroendocrine research confirms the association of these syndromes with dysregulation in a major stress response system, the hypothalamic-pituitary-adrenal (HPA) axis. However, the proposal that depression and anxiety symptoms and diagnoses are associated with problematic HPA responses to close relationship stress has not been directly tested. We examined 196 heterosexual dating couples' depression and anxiety symptoms and diagnoses, assessed with questionnaires and diagnostic interviews, in relation to cortisol responses to discussion of an unresolved relationship conflict. Participants provided seven salivary samples in anticipation of and directly following the discussion, and throughout an hour-long recovery period, which were assayed for cortisol. Multilevel models of the HPA response predicted by symptoms or diagnoses showed that women's depressive symptoms predicted attenuated cortisol levels, with a flatter response curve. In contrast, men's depression symptoms and women's anxiety symptoms and diagnoses predicted higher cortisol levels. These findings highlight the importance of examining sex differences in responses to interpersonal stressors for understanding HPA dysregulation in internalizing psychopathology.

Measuring nerve growth factor in saliva by immunoassay: A cautionary note.

Nerve growth factor (NGF), a neurotrophin, modulates a diverse set of physiologic processes in the nervous, immune, and endocrine systems. Studies suggest that NGF can be measured in saliva (sNGF). Historically, the method for measuring sNGF involves the off-label use of an enzyme immunoassay designed for use with cell-culture supernatants/tissue extracts (Nam et al., 2007; Ruhl et al., 2004). In a series of experiments we reveal this measurement strategy is subject to non-specific interference by constituents present in oral fluids. We conclude that the measurement of sNGF by this assay is not optimal for use with oral fluid specimens.

Secretory IgA reactivity to social threat in youth: Relations with HPA, ANS, and behavior.

Although the role of immune marker secretory immunoglobulin A (SIgA) in stress-related health outcomes is gaining recognition, SIgA responsiveness to acute stress has rarely been assessed in adults, and not at all in children. This study was designed to clarify developmental origins of differential immune function-related health risks by investigating youth SIgA responses to psychosocial stressors, including both normative responses and variability related to behavioral problems. Children and adolescents from a larger study (n=82) gave 6 saliva samples during a laboratory session in which they were exposed to a series of performance or interpersonal stressors. Samples were assayed for SIgA, as well as cortisol (representing hypothalamic-pituitary-adrenal axis activity) and alpha-amylase (sAA; representing autonomic nervous system activity). Behavioral problems were assessed with parent-report measures of youth internalizing and externalizing. Youth SIgA trajectories followed a normative pattern of reactivity and recovery around the stressors; however, these responses were blunted in youth with higher externalizing scores. SIgA showed differential associations with cortisol and sAA, and with positive and negative affect; whereas overall levels of SIgA related to cortisol output and positive affect, changes in SIgA over time synchronized with changes in sAA and negative affect. In contrast to SIgA, neither cortisol nor sAA related significantly to behavioral problems. Implications for the role of SIgA during psychosocial stress in the development of immune function-related health risks are discussed.

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high < SS/low = L/high < L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings.