Unique and interactive effects of threat and deprivation on latent trait cortisol among emerging adults.

Though considerable work supports the Dimensional Model of Adversity and Psychopathology, prior research has not tested whether the dimensions-threat (e.g., abuse) and deprivation (e.g., neglect)-are uniquely related to salivary trait indicators of hypothalamic pituitary adrenal (HPA) axis activity. We examined the unique and interactive effects of threat and deprivation on latent trait cortisol (LTC)-and whether these effects were modified by co-occurring adversities. Emerging adults (n = 90; Mage = 19.36 years; 99.88% cisgender women) provided salivary cortisol samples four times a day (waking, 30 min and 45 min postwaking, bedtime) over three 3-day measurement waves over 13 weeks. Contextual life stress interviews assessed early adversity. Though the effects varied according to the conceptualization of early adversity, overall, threat-but not deprivation, nor other co-occurring adversities-was uniquely associated with the across-wave LTC. Specifically, the incidence and frequency of threat were each negatively related to the across-wave LTC. Threat severity was also associated with the across-wave LTC, but only among those with no deprivation. Finally, the effects of threat were modified by other co-occurring adversities. Findings suggest that threat has unique implications for individual differences in HPA axis activity among emerging adults, and that co-occurring adversities modify such effects.

Early adversity and depressive symptoms among early adolescent girls: the mediating role of exposure to recent interpersonal acute stress.

Early adversity confers risk for depression in part through its association with recent (i.e., proximal) acute stress. However, it remains unresolved whether: a) early adversity predicts increases in recent acute stress over time; b) all - or only certain types - of recent events mediate the relationship between early adversity and depression; and c) early adversity places individuals at greater risk for depression via greater exposure to independent (i.e., fateful) interpersonal events or via greater generation of dependent (i.e., partially self-initiated) interpersonal events (i.e., stress generation) or both. These questions were examined in a 3-wave longitudinal study of early adolescent girls (N = 125; M = 12.35 years [SD = .77]) with no history of diagnosable depression using contextual life stress and diagnostic interviews. Path analyses indicated that increases in past-year acute interpersonal, but not non-interpersonal, stress mediated the link between early adversity and depressive symptoms. The mediating role of interpersonal events was limited to independent ones, suggesting increases in interpersonal event exposure, not interpersonal stress generation, acted as a mediator. Finally, findings support prior evidence that early adversity may not directly predict future depressive symptoms. Implications for understanding the role of recent stress in the association between early adversity and adolescent depression are discussed.

Stress sensitization to depression following childhood adversity: Moderation by HPA axis and serotonergic multilocus profile scores.

Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic-pituitary-adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a "gene-by-environment-by-environment" interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.

Overestimating Self-Blame for Stressful Life Events and Adolescents' Latent Trait Cortisol: The Moderating Role of Parental Warmth.

Cognitive interpretations of stressful events impact their implications for physiological stress processes. However, whether such interpretations are related to trait cortisol-an indicator of individual differences in stress physiology-is unknown. In 112 early adolescent girls (M age = 12.39 years), this study examined the association between self-blame estimates for past year events and latent trait cortisol, and whether maternal warmth moderated effects. Overestimating self-blame (versus objective indices) for independent (uncontrollable) events was associated with lower latent trait cortisol, and maternal warmth moderated the effect of self-blame estimates on latent trait cortisol for each dependent (at least partially controllable) and interpersonal events. Implications for understanding the impact of cognitive and interpersonal factors on trait cortisol during early adolescence are discussed.

Cortisol awakening response and additive serotonergic genetic risk interactively predict depression in two samples: The 2019 Donald F. Klein Early Career Investigator Award Paper.

BACKGROUND: The serotonin system and hypothalamic pituitary-adrenal (HPA)-axis are each implicated in the pathway to depression; human and animal research support these systems' cross-talk. Our work implicates a 5-variant additive serotoninergic multilocus genetic profile score (MGPS) and separately the cortisol awakening response (CAR) in the prospective prediction of depression; other work has shown that the serotonin transporter polymorphism 5HTTLPR predicts CAR and interacts with the CAR to predict depression. METHODS: We tested the hypothesis that a 6-variant MGPS (original plus 5HTTLPR) would interact with CAR to predict prospective depressive episode onsets in 201 emerging adults using four annual follow-up interviews. We also tested whether MGPS predicted CAR. We attempted replication of significant findings in a sample of 77 early adolescents predicting depression symptoms. RESULTS: In sample 1, MGPS did not significantly predict CAR. MGPS interacted with CAR to predict depressive episodes; CAR slopes for depression steepened as MGPS increased, for risk or protection. No single variant accounted for results, though CAR's interactions with 5HTTLPR and the original MGPS were both significant. In sample 2, the 6-variant MGPS significantly interacted with CAR to predict depression symptoms. CONCLUSIONS: Higher serotonergic MGPS appears to sensitize individuals to CAR level-for better and worse-in predicting depression.

Early adversity and internalizing symptoms in adolescence: Mediation by individual differences in latent trait cortisol.

Research suggests that early adversity places individuals at risk for psychopathology across the life span. Guided by concepts of allostasis and allostatic load, the present study examined whether early adversity contributes to the development of subsequent internalizing symptoms through its association with traitlike individual differences in hypothalamic-pituitary-adrenal axis regulation. Early adolescent girls (n = 113; M age = 12.30 years) provided saliva samples at waking, 30 min postwaking, and bedtime over 3 days (later assayed for cortisol). Objective contextual stress interviews with adolescents and their mothers were used to assess the accumulation of nine types of early adversity within the family environment. Greater early adversity predicted subsequent increases in internalizing symptoms through lower levels of latent trait cortisol. Traitlike individual differences in hypothalamic-pituitary-adrenal axis activity may be among the mechanisms through which early adversity confers risk for the development of psychopathology.

Rumination, Excessive Reassurance Seeking, and Stress Generation Among Early Adolescent Girls.

Nolen-Hoeksema proposed that rumination increases stressful events and circumstances; however, few studies have examined this question. Thus, we explored whether (a) rumination predicted increases in the generation of chronic and acute stress, (b) excessive reassurance seeking (ERS) mediated links between rumination and stress generation, (c) rumination increased exposure to acute independent (uncontrollable) stress, and (d) rumination predicted chronic stress generation in certain domains, but not others. These questions were examined in a 1-year study of 126 early adolescent girls ( M age = 12.39 years) using contextual objective stress interviews. Findings indicated that rumination predicted increases in acute dependent interpersonal stress and chronic interpersonal stress, and ERS mediated these associations. Moreover, rumination was not associated with acute independent stress. Finally, the effect of rumination on chronic stress generation was most salient in adolescents' romantic lives and in parent-adolescent relationships. These findings suggest that ruminators create stressful interpersonal environments.

Childhood adversity moderates the influence of proximal episodic stress on the cortisol awakening response and depressive symptoms in adolescents.

Childhood adversity (CA) is known to predict sensitization to proximal stressors. Researchers have suggested that disruptions in hypothalamus-pituitary-adrenal axis functioning may be a biological mechanism. If so, CA may predict altered associations between proximal life stress and markers of cortisol secretion. We examined whether CA moderates associations between recent episodic stress and (a) the cortisol awakening response (CAR), and (b) depressive symptoms, in 241 adolescents aged 14-17 years (cortisol n = 196). Salivary cortisol was sampled at 0, 30, and 60 min postawakening for 2 days. The CAR was calculated as the area under the curve with respect to increase and waking cortisol. CA and episodic stress were assessed using contextual-threat-method-coded objective interviews. CA significantly interacted with episodic stress to predict both the CAR and depression. Among those with low CA, episodic stress predicted increased CAR but did not predict depression. For adolescents with high CA, episodic stress predicted lower CAR and higher depression. These interactions were found only for independent (uncontrollable, fateful) events, and not for dependent (self-generated) stress. Increased allostatic load resulting from CA exposure may interfere with adolescents' ability to optimally regulate their CAR in relation to recent stress, contributing to increased depression risk.

Rumination in Early Adolescent Girls: Interactive Contributions of Mother-Adolescent Relationship Quality and Maternal Coping Suggestions.

Research suggests that rumination places adolescents at risk for psychopathology. However, little is known about the association between parenting and rumination. Moreover, relevant theoretical models suggest that parents contribute to the development of rumination both explicitly through their suggestions about how to cope and implicitly through the context of the mother-adolescent relationship. However, prior work has not examined implicit and explicit factors within the same investigation, precluding exploration of their unique and interactive effects. To address these gaps, the present study examined links between mother-adolescent relationship quality, maternal coping suggestions, and adolescent rumination. Participants were early adolescent girls (M age = 12.41 years) and their primary female caregivers. Findings suggested that maternal disengagement suggestions and mother-adolescent relationship quality were each uniquely associated with adolescent rumination. Moreover, the effect of maternal disengagement suggestions depended on the level of maternal engagement suggestions and mother-adolescent relationship quality. Follow-up analyses revealed that these findings were specific to the maladaptive ruminative brooding component of rumination. Future directions for research were elaborated.

Daily and trait rumination: diurnal cortisol patterns in adolescent girls.

Rumination is a maladaptive form of emotion regulation associated with psychopathology. Research with adults suggests that rumination covaries with diurnal cortisol rhythms, yet this has not been examined among adolescents. Here, we examine the day-to-day covariation between rumination and cortisol, and explore whether trait rumination is associated with alterations in diurnal cortisol rhythms among adolescent girls. Participants (N = 122) provided saliva samples 3 times per day over 3 days, along with daily reports of stress and rumination, questionnaires assessing trait rumination related to peer stress, and diagnostic interviews assessing depression and anxiety. Greater rumination than usual during the day was associated with lower cortisol awakening responses the following morning, but this effect was not significant after accounting for wake time and an objective measure of adherence to the saliva sampling protocol. Trait rumination was associated with lower average cortisol levels at waking and flatter diurnal slopes, accounting for wake time, protocol compliance, and other factors. These patterns may help to explain why rumination is related to the development of psychopathology.

Individual and Day-to-Day Differences in Active Coping Predict Diurnal Cortisol Patterns among Early Adolescent Girls.

Prior work has identified alterations in activity of the hypothalamic-pituitary-adrenal axis as a potential mechanism underlying stress-induced emotional health problems, which disproportionately impact girls beginning in mid-adolescence. How adolescent girls differ from one another in dispositional coping tendencies and shift specific coping strategies in response to varying stressors have been theorized as important predictors of their adaptation, health, and well-being during this dynamic period of development. The goal of this study was to examine whether individual and day-to-day (within-person) differences in adolescent girls' coping responses are associated with daily patterns of hypothalamic-pituitary-adrenal axis activity, indexed by cortisol. Participants were 122 early adolescent girls (M age = 12.39) who provided three saliva samples per day for 3 days and completed daily coping reports, as well as a standard coping survey. Participants and primary caregivers also completed objective life stress interviews. On average, girls who were more likely to respond to interpersonal stress with voluntary engagement (active) coping exhibited generally adaptive daily physiological regulation-steeper diurnal cortisol slopes, lower total diurnal cortisol output, and lower cortisol awakening responses. Chronic interpersonal stress level significantly moderated these associations in different ways for two distinct components of the diurnal pattern-the slope and cortisol awakening responses. Regarding within-person differences, using active coping more than usual was associated with higher waking cortisol the following morning, which may help to prepare adolescent girls for perceived daily demands. These findings highlight the interactive influence of stress and coping in the prediction of daily hypothalamic-pituitary-adrenal axis activity and support the stress-buffering role of active coping for adolescent girls.

Respiratory Health and Related Quality of Life in Patients with Congenital Agammaglobulinemia in the Northern Region of the UK.

INTRODUCTION: Patients with congenital agammaglobulinemia, characterized by a defect in B lymphocyte differentiation causing B alymphocytosis, require life-long IgG replacement. There is scant literature regarding the effectiveness of IgG treatment at preventing mucosal (particularly sinopulmonary tract) infection and whether current management adequately restores "normal" health and quality of life (QoL). We aimed to document infective episodes pre- and post-commencing IgG replacement, determine any change in lung function and structure and assess respiratory status and QoL in a cohort of patients treated in Newcastle. METHODS: Clinical data were extracted from medical records of 15 patients identified from the immunology database, focusing on infective episodes, serial chest CT and spirometry results. Thirteen patients completed a selection of standardized and validated questionnaires assessing physical health, respiratory health and QoL. RESULTS: Pediatric patients on IgG therapy suffered fewer infections per patient year (0.74) than adults (2.13). 6/14 patients showed deteriorating respiratory status despite adequate therapy. Health questionnaires revealed a significant burden of respiratory disease on a patient's life. CONCLUSION: Clinical data showed patients with congenital agammaglobulinemia receiving immunoglobulin therapy retained a higher than average infection rate, most of which affected mucosal barriers. Most patients self-reported worse respiratory symptoms, a lower respiratory-related QoL and a lower general health QoL relative to a healthy population. Most participants had progressive structural lung damage and decreased lung function. These results suggest that current management is not entirely effective at preventing deterioration of respiratory health or restoring QoL.

Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016.

Marital Quality Spillover and Young Children's Adjustment: Evidence for Dyadic and Triadic Parenting as Mechanisms.

Research has evidenced support for the spillover model, which posits that parents' marital functioning influences child adjustment by eroding parenting and coparenting in dyadic (mother-child and father-child) and triadic (mother-father-child) contexts. However, prior work has not simultaneously investigated dyadic and triadic parenting as mechanisms of spillover. Furthermore, although evidence indicates that the marital system affects child adjustment by influencing parents' behavior, research has not explored whether child behaviors in parent-child interactions also serve as mechanisms. To address these gaps, we examined the spillover model using observational measures of parent and child behavior in parent-child dyadic interactions as well as coparenting in triadic interactions. We also explored parent and child gender differences in spillover effects. Participants were families with children 3 to 6 years of age (n=149; 62% Caucasian). Findings indicated that marital functioning influences child adjustment by disrupting parent-child interactions in dyadic and triadic contexts, although results differed by child/parent gender and outcome examined. First, children's responsiveness to their mothers emerged as a significant mechanism of spillover effects for boys' internalizing and girls' externalizing behavior. Second, for girls and boys, marital functioning was indirectly related to children's internalizing and externalizing behavior through reductions in coparenting warmth. Finally, there was little evidence that parent gender moderated the indirect effect of dyadic parenting, except that child responsiveness to mothers (vs. to fathers) was more strongly related to child adjustment. These findings underscore the need for interventions targeting dyadic and triadic parent-child interactions in the face of marital distress.

A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom.

BACKGROUND: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care. OBJECTIVE: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients. METHODS: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data. RESULTS: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home. CONCLUSIONS: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients.

Love hurts (in more ways than one): specificity of psychological symptoms as predictors and consequences of romantic activity among early adolescent girls.

OBJECTIVE: Research has linked adolescent romantic and sexual activities to depressive symptoms. The current study examines whether such activities are uniquely linked to depressive symptoms versus symptoms of other disorders (including anxiety, externalizing, and eating disorders), and whether co-occurring symptoms more precisely account for the association between depressive symptoms and romantic involvement. METHOD: Early adolescent girls (N = 83; mean age = 13.45) participated in baseline and 1-year follow up data collection. RESULTS: Romantic (i.e., dating and sexual) activities were longitudinally related to numerous types of symptoms. The association between depressive symptoms and romantic variables remained when considering co-occurring symptoms. Girls with more comorbid disorders reported more romantic activities. CONCLUSIONS: Results suggest that the maladaptive consequences and precipitants of adolescent romantic activities extend beyond depression, but also imply that this association is not secondary to comorbid symptoms. Future work should clarify causal pathways.

Does stress predict the development of internalizing symptoms in middle childhood? An examination of additive, mediated, and moderated effects of early family stress, daily interpersonal stress, and physiological stress.

Early life stress, daily life experiences, and the stress responsive hypothalamic-pituitary-adrenal (HPA) axis have each been examined as predictors of the development of psychopathology. Rarely have researchers attempted to understand the covariation or interaction among these stress domains using a longitudinal design in the prediction of symptoms of internalizing psychopathology, particularly during childhood. This study examined early family stress, daily interpersonal stress, indicators of diurnal cortisol, and internalizing symptoms in a racially/ethnically and socioeconomically diverse sample of twins (N = 970 children; Mage at outcome = 9.73; 52% female; 23.7% Hispanic/Latino, 58.8% White; 30% below middle class; Lemery-Chalfant et al., 2019). An additive model of stress, a stress mediation model, and a stress sensitization framework model each delineated potential pathways linking stress and internalizing symptoms. Supporting additive pathways, multilevel models showed that all 3 stress indicators uniquely predicted internalizing symptoms. There was a significant indirect path from early family stress to 9 year internalizing symptoms through interpersonal stress, supporting stress mediation. Family stress moderated the association between interpersonal stress and internalizing symptoms, though not in the direction that would support stress sensitization. Child stress, including daily interpersonal stress and HPA axis activity, and internalizing symptoms are prevalent and family stress is a significant precursor to child internalizing symptoms across child development. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Individual differences in latent trait cortisol (LTC): Implications for the onset and course of future depressive symptoms.

Research suggests that various indicators of hypothalamic pituitary adrenal (HPA) axis activity prospectively predict depression, but few studies have evaluated whether trait indicators of HPA axis activity are related to depression. Further, no prior study has examined links between trait cortisol and psychopathology using a trait indicator that captures HPA axis activity over multiple time points. Here we examined whether we could construct an across-wave latent trait cortisol (LTC) factor using cortisol samples collected over 13 weeks, and whether the across-wave LTC prospectively predicted new depressive symptom onsets and symptom duration. Emerging adults (n = 85; M age = 19.37 years) provided salivary cortisol samples four times a day (waking, 30 min and 45 min post-waking and bedtime) over three 3-day measurement waves separated by 6 weeks. Diagnostic interviews at 3 timepoints (baseline, 1- and 2.5 years post-baseline) assessed lifetime and current depressive symptoms. Results indicated that the across-wave LTC predicted new onsets of depressive symptoms and longer symptom duration. Follow-up tests revealed that the link between the across-wave LTC and new onsets was not significant after adjusting for past depressive symptoms. These findings suggest that an indicator of individual differences in HPA axis regulation has implications for depressive symptom onsets and course.

What I like about you: the association between adolescent attachment security and emotional behavior in a relationship promoting context.

Because the ability to flexibly experience and appropriately express emotions across a range of developmentally relevant contexts is crucial to adaptive functioning, we examined how adolescent attachment security may be related to more functional emotional behavior during a relationship promoting interaction task. Data were collected from 74 early adolescent girls (Mean age 13.45 years; SD = 0.68; 89% Caucasian) and their primary caregiver. Results indicated that, regardless of the parent's interaction behavior and the level of stress in the parent-adolescent relationship, greater adolescent security was associated with more positive and less negative behavioral displays, including greater positivity, greater coherence of verbal content and affect, less embarrassment, and less emotional dysregulation in response to a situational demand for establishing intimacy with the parent. Implications for encouraging and fostering adolescents' capacity to respond to interpersonal contexts in ways that promote the relationship are discussed.