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.

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.

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).

Dopaminergic Genetic Variation in Young Adolescents: Associations with Sensation-Seeking.

Deficient reward functioning, including reward-related personality, is implicated in depression's etiology. A dopaminergic genetic multilocus genetic profile score (MGPS) has previously been associated with neural reward responsivity but, despite theoretical basis, has not been studied with reward-related personality. Such research is needed to elucidate associations between genetic variation and reward-related personality in a developmentally sensitive population. In the present study, we examined associations between dopaminergic MGPS's and self-report reward-related personality in two young adolescent samples aged 10-15 years old (Sample 1: N = 100 girls, 82% White, 18% Other; Sample 2: N = 141, 65 girls, 76 boys, 89.36% White, 10.64% Other) using an established MGPS and an augmented MGPS. A "mini" meta-analysis synthesized results across samples. In Sample 1, an exploratory mediation analysis intended to gauge effect size for future work tested a path between the MGPS and depression through significant reward traits. In each independent sample, both MGPS's showed significant associations with sensation-seeking but not social drive, a pattern that persisted following correction. Effect sizes of novel variants were at least as robust as established variants, suggesting their added utility. Additionally, the exploratory mediation analysis suggested no noteworthy indirect effect, but a small (R2 = 0.022), statistically non-significant direct effect of the MGPS predicting prospective depressive symptoms. Results suggest that dopaminergic genetic variation is associated with the reward-related personality trait of sensation seeking but not social drive. Additional work is needed to probe whether sensation seeking may be a path through which this genetic variation confers depression risk.

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.

Serotonergic multilocus genetic variation moderates the association between major interpersonal stress and adolescent depressive symptoms: Replication and candidate environment specification.

Serotonin-linked genetic risk and stressful life event (SLE) interaction research has been criticized for using single genetic variants with inconsistent replicability. A recent study showed that a multilocus genetic profile score (MGPS) capturing additive risk from five serotonin-linked polymorphisms moderated the association between major interpersonal SLEs and depression, but no subsequent replication attempts have been reported. Moreover, major interpersonal SLEs have been suggested as "candidate environments" for this MGPS, but it has never been demonstrated that gene-environment interactions (G × Es) for major interpersonal SLEs are significantly stronger than for other contexts. Adolescents (N = 241) completed contextual-threat life stress interviews and clinical interviews assessing depressive symptoms, and provided DNA. MGPS intensified the major interpersonal stress-depression association; the interaction accounted for 4% of depressive symptom variance. Genetic moderation was statistically unique to major interpersonal stress versus other environments. Extending previous findings, results support an MGPS approach and underscore the cruciality of the G × E candidate environment.

The cortisol awakening response (CAR) interacts with acute interpersonal stress to prospectively predict depressive symptoms among early adolescent girls.

The cortisol awakening response (CAR) has been shown to prospectively predict depression, but it remains unresolved whether a greater CAR predicts risk independently of subsequent acute stress, or whether greater CAR indicates increased vulnerability to subsequent acute stress. Further, no prior work has evaluated whether the CAR increases vulnerability to certain types of acute stress, but not others, in predicting depression. To address these gaps, we investigated whether the CAR predicted depressive symptoms alone and in interaction with acute interpersonal stress in a one-year longitudinal study of 86 early adolescent girls with no history of diagnosable depression. To index the CAR, adolescents collected saliva at waking and 30-minutes past waking for 3 days; compliance with the sampling protocol was electronically monitored. Diagnostic and objective contextual stress interviews were used to quantify acute stress in the 2-months prior to worst depressive symptom onset during the follow-up. Supporting hypotheses, results indicated that greater CAR predicted greater depressive symptoms, and interacted with acute interpersonal stress in predicting depressive symptoms. Further, the CAR interacted with acute dependent (i.e., at least partially arising from the person's behavior) interpersonal stress in predicting depressive symptoms. In contrast, the CAR did not interact with acute non-interpersonal stress nor acute interpersonal independent (i.e., fateful) stress in predicting depressive symptoms. These results further refine circumstances in which the CAR is predictive of depressive symptoms among early adolescent girls, and highlight the importance of focusing on etiologically relevant stress when testing interactions between physiological stress indicators and environmental stress.

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.

Individual differences in early adolescents' latent trait cortisol: Interaction of early adversity and 5-HTTLPR.

The present study aimed to examine the interaction of 5-HTTLPR and early adversity on trait-like levels of cortisol. A community sample of 117 early adolescent girls (M age=12.39years) provided DNA samples for 5-HTTLPR genotyping, and saliva samples for assessing cortisol 3 times a day (waking, 30min post-waking, and bedtime) over a three-day period. Latent trait cortisol (LTC) was modeled using the first 2 samples of each day. Early adversity was assessed with objective contextual stress interviews with adolescents and their mothers. A significant 5-HTTLPR×early adversity interaction indicated that greater early adversity was associated with lower LTC levels, but only among individuals with either L/L or S/L genotype. Findings suggest that serotonergic genetic variation may influence the impact of early adversity on individual differences in HPA-axis regulation. Future research should explore whether this interaction contributes to the development of psychopathology through HPA axis functioning.

Interpersonal dysfunction in personality disorders: A meta-analytic review.

Personality disorders are defined in the current psychiatric diagnostic system as pervasive, inflexible, and stable patterns of thinking, feeling, behaving, and interacting with others. Questions regarding the validity and reliability of the current personality disorder diagnoses prompted a reconceptualization of personality pathology in the most recent edition of the psychiatric diagnostic manual, in an appendix of emerging models for future study. To evaluate the construct and discriminant validity of the current personality disorder diagnoses, we conducted a quantitative synthesis of the existing empirical research on associations between personality disorders and interpersonal functioning, defined using the interpersonal circumplex model (comprising orthogonal dimensions of agency and communion), as well as functioning in specific relationship domains (parent-child, family, peer, romantic). A comprehensive literature search yielded 127 published and unpublished studies, comprising 2,579 effect sizes. Average effect sizes from 120 separate meta-analyses, corrected for sampling error and measurement unreliability, and aggregated using a random-effects model, indicated that each personality disorder showed a distinct profile of interpersonal style consistent with its characteristic pattern of symptomatic dysfunction; specific relationship domains affected and strength of associations varied for each personality disorder. Overall, results support the construct and discriminant validity of the personality disorders in the current diagnostic manual, as well as the proposed conceptualization that disturbances in self and interpersonal functioning constitute the core of personality pathology. Importantly, however, contradicting both the current and proposed conceptualizations, there was not evidence for pervasive dysfunction across interpersonal situations and relationships. (PsycINFO Database Record

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.

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.

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 differences in early adolescents' latent trait cortisol (LTC): Relation to recent acute and chronic stress.

Research suggests that environmental stress contributes to health by altering the regulation of the hypothalamic pituitary adrenal (HPA) axis. Recent evidence indicates that early life stress alters trait indicators of HPA axis activity, but whether recent stress alters such indicators is unknown. Using objective contextual stress interviews with adolescent girls and their mothers, we examined the impact of recent acute and chronic stress occurring during the past year on early adolescent girls' latent trait cortisol (LTC) level. We also examined whether associations between recent stress and LTC level: a) varied according to the interpersonal nature and controllability of the stress; and b) remained after accounting for the effect of early life stress. Adolescents (n=117;M age=12.39years) provided salivary cortisol samples three times a day (waking, 30min post-waking and bedtime) over 3days. Results indicated that greater recent interpersonal acute stress and greater recent independent (i.e., uncontrollable) acute stress were each associated with a higher LTC level, over and above the effect of early adversity. In contrast, greater recent chronic stress was associated with a lower LTC level. Findings were similar in the overall sample and a subsample of participants who strictly adhered to the timed schedule of saliva sample collection. Implications for understanding the impact of recent stress on trait-like individual differences in HPA axis activity are discussed.

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.