Relationship of cortisol and alpha amylase to behavioral engagement under three levels of negative evaluative psychosocial stress.

Despite that behavioral engagement is integral to mental health, surprisingly little is known about the relationship of psychosocial stress and behavioral engagement. The current study developed an observer-rated measure of behavioral engagement for lab-based stress inductions, then examined its relationship with stress-responsive biomarkers and affect. Young adults (N = 109, Mage=19.4, SDage=1.59, 57% female) completed one of three Trier Social Stress Test (TSST) conditions-non-stressful Control, Intermediate, or an Explicit Negative Evaluative-and at four timepoints provided self-reports of positive and negative affect and saliva samples for cortisol and salivary alpha-amylase (sAA). Trained study staff (experimenters and TSST judges) completed a programmed questionnaire measure of the novel behavioral engagement measure after the participants completed the TSST. Psychometric review and EFA of the behavioral engagement items resulted in a final 8-item measure with good interrater reliability and well-fitting 2-factor structure, capturing Persistence (4 items; loadings=.41-.89), and Quality of Speech (4 items; loadings=.53-.92). Results indicated that the relationship of positive affect growth and biomarker level to behavioral engagement varied substantially as a function of context: As negative evaluation level strengthened, behavioral engagement became more tightly associated with relative preservation of positive affect. For both cortisol and sAA, the relationship between biomarker levels (but not reactivity) and behavioral engagement varied significantly by condition, such that under milder conditions and elevated levels of biomarkers, engagement was greater, but under Explicit Negative Evaluation, and elevated levels of biomarkers, engagement was less, suggesting behavioral withdrawal. Findings reveal the critical role of context-especially negative evaluation-in the relationship of biomarkers with behavioral engagement.

Effects of trauma-focused rumination among trauma-exposed individuals with and without posttraumatic stress disorder: An experiment.

Rumination, or thinking repetitively about one's distress, is a risk factor for posttraumatic stress disorder (PTSD). Current theories suggest that rumination contributes to PTSD symptoms directly, by increasing negative reactions to trauma cues (i.e., symptom exacerbation), or represents a form of cognitive avoidance, if verbal ruminations are less distressing than trauma imagery. The goal of this study was to test the symptom exacerbation and cognitive avoidance accounts of trauma-focused rumination. We recruited 135 trauma-exposed participants (n = 60 diagnosed with PTSD) and randomly assigned them to ruminate about their trauma, distract themselves, or engage in trauma imagery. For individuals with and without PTSD, rumination led to larger increases in subjective distress (i.e., negative affect, fear, sadness, subjective arousal, valence) than distraction, ηp 2 s = .04-.13, but there were no differences between rumination and imagery ηp 2 s = .001-.02. We found no evidence that rumination or imagery elicited physiological arousal, ds = 0.01-0.19, but did find that distraction reduced general physiological arousal, as measured by heart rate, relative to baseline, d = 0.84, which may be due to increases in parasympathetic nervous system activity (i.e., respiratory sinus arrhythmia), d = 0.33. These findings offer no support for the avoidant function of rumination in PTSD. Instead, the findings were consistent with symptom exacerbation, indicating that rumination leads directly to emotional reactivity to trauma reminders and may be a fruitful target in PTSD intervention.

The effect of acute exercise on the cortisol awakening response.

The effects of acute exercise on the cortisol awakening response (CAR), characterized by the rapid increase in cortisol concentrations within the 30-45 min following sleep offset has yet to be fully elucidated. Thus, our study investigated the effects of late-evening acute exercise on the CAR the following morning. We hypothesized that exercise would have a significant effect on the CAR the following morning. Twelve participants (mean (SD): age = 23 (4) years; mass = 76.8 (8.7) kg; height = 175.6 (5.0) cm; [Formula: see text]O2max = 48.9 (7.5) ml.kg-1.min-1) reported to the laboratory in the evening (1800 h) on two occasions and were randomly assigned to either exercise for one hour (70-75% of maximal power output) or rest condition. Blood and saliva samples were assayed for cortisol. Mixed-effects models determined the effect of exercise on the cortisol response post-waking in both blood and saliva. Participants demonstrated an average exercise-induced increase in circulating cortisol of 477.3%, with actual mean (SD) heart rate relative to maximum of 87.04% (6.14%). Model results demonstrated a negative effect for exercise condition when modeling the serum and salivary cortisol responses to awakening via a quadratic growth model (serum, ßCondition = - 42.26 [95% CI - 64.52 to - 20.01], p < 0.001; saliva, ßCondition = - 11.55 [95% CI - 15.52 to - 7.57], p < 0.001). These results suggest that cortisol concentrations in saliva and blood are significantly lower the morning following a prior evening exercise session. Therefore, the CAR may serve as a useful biomarker to monitor responses to exercise training, although the underlying mechanism for these decreases in the CAR should be investigated further.

Experiences of adversity in childhood and adolescence and cortisol in late adolescence.

Early life adversity influences the diurnal cortisol rhythm, yet the relative influence of different characteristics of adversity remains unknown. In this study, we examine how developmental timing (childhood vs. adolescence), severity (major vs. minor), and domain of early life adversity relate to diurnal cortisol rhythms in late adolescence. We assessed adversity retrospectively in early adulthood in a subsample of 236 participants from a longitudinal study of a diverse community sample of suburban adolescents oversampled for high neuroticism. We used multilevel modeling to assess associations between our adversity measures and the diurnal cortisol rhythm (waking and bedtime cortisol, awakening response, slope, and average cortisol). Major childhood adversities were associated with flatter daily slope, and minor adolescent adversities were associated with greater average daily cortisol. Examining domains of childhood adversities, major neglect and sexual abuse were associated with flatter slope and lower waking cortisol, with sexual abuse also associated with higher cortisol awakening response. Major physical abuse was associated with higher waking cortisol. Among adolescent adversities domains, minor neglect, emotional abuse, and witnessing violence were associated with greater average cortisol. These results suggest severity, developmental timing, and domain of adversity influence the association of early life adversity with stress response system functioning.

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.

Measurement invariance of the Interpersonal Needs Questionnaire (INQ-15) across sexual orientation, gender identity, and race/ethnicity in a sample of sexual minority young adults.

Sexual minority (e.g., gay, lesbian, bisexual) people are at increased risk for suicidal thoughts and behaviors compared to their heterosexual peers. The interpersonal theory of suicide proposes that perceived burdensomeness and thwarted belongingness are central to the desire to die, and both are associated with suicidal ideation in sexual minority samples. The Interpersonal Needs Questionnaire (INQ) was developed to measure these risk factors and has become the most commonly used measure. However, it is unknown whether the INQ demonstrates similar measurement properties across subgroups of sexual minority people. Therefore, the goal of this study was to examine whether the 15-item version of the INQ exhibited measurement invariance (MI) across sexual orientation (gay/lesbian vs. bi +), gender identity (cisgender men vs. cisgender women vs. transgender/gender diverse individuals), and race/ethnicity (non-Latinx White individuals vs. people of color) in a sample of 792 sexual minority young adults (ages 18-29). A series of multigroup measurement invariance models indicated that the INQ-15 met strict invariance (i.e., equal factor loadings, item intercepts, and residual variances) across all three dimensions of identity. This indicates that it can be used and compared across diverse samples of sexual minority young adults. Results also indicated that perceived burdensomeness was greater for transgender/gender diverse individuals than for cisgender men and women, and that perceived burdensomeness and thwarted belongingness were greater for people of color than for non-Latinx White individuals. In contrast, gay/lesbian and bi + individuals did not differ. Additional research is needed to understand the factors that account for these group differences. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Additive serotonergic genetic sensitivity and cortisol reactivity to lab-based social evaluative stress: Influence of severity across two samples.

Prior work demonstrates that an additive serotonergic multilocus genetic profile score (MGPS) predicts amplified risk for depression following significant life stress, and that it interacts with elevations in the cortisol awakening response to predict depression. The serotonin system and HPA-axis have bidirectional influence, but whether this MGPS predicts acute cortisol reactivity, which might then serve as a mechanism for depression, is unknown. Our prior work suggests that depression risk factors predict blunted cortisol reactivity to explicit negative evaluative lab-based stress. Thus, we hypothesized that a 4-variant serotonergic MGPS (three SNPs from the original 5-variant version plus 5HTTLPR) would predict blunted cortisol reactivity to explicit negative evaluative stress versus a control. In Sample 1, growth curve modeling showed that the MGPS predicted heightened cortisol reactivity (p = 0.0001) in an explicitly negative evaluative Trier Social Stress Test variant (TSST) versus a control condition among non-depressed emerging adults (N = 152; 57% female). In Sample 2, 125 males completed the Socially Evaluative Cold Pressor Test (SECPT), an ambiguously negative evaluative manipulation; findings displayed a similar pattern but did not reach statistical significance (ps.075-.091). A participant-level meta-analysis of the two samples demonstrated a significant effect of negative evaluation severity, such that the MGPS effect size on reactivity increased linearly from control to SECPT to an explicitly negative evaluative TSST. Findings indicate that this MGPS contributes to sensitivity to social threat and that cortisol dysregulation in the context of social stress may be one mechanism by which this MGPS contributes to depression.

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.

The impact of prior day sleep and physical activity on the cortisol awakening response.

The cortisol awakening response (CAR) describes the increase in cortisol within the first 30-60 min after waking from nocturnal sleep, and is a common biomarker used within psychoneuroendocrinology, but the effect of sleep on the CAR is currently unclear. A previous study suggested that reported discrepancies may be due to other lifestyle behaviors such as physical activity; given the role of the CAR in energy regulation and preparation for the day, it is theoretically plausible that activity level would influence the CAR. However, no study has yet utilized objective monitoring of day-to-day sleep and physical activity to investigate potential effects on the CAR. This study aimed to test the hypotheses that either sleep duration or sleep quality would interact with the prior 24 h' physical activity to predict the CAR on the following morning. Salivary samples were collected from 85 young adults (mean = 19.1 years, SD = 1.89) immediately after waking from nocturnal sleep and again 30 min after waking; two complete and consecutive days were used. Participants wore accelerometers (ActiGraph, wGT3X-BT) throughout this phase of a larger study, which provided objective measures of sleep duration, number of awakenings, and amount of physical activity. Mixed-effects models with post-hoc regions of significance decompositions tested the hypothesized interaction effects. Results demonstrated a significant interaction between prior day sleep duration and physical activity predicting the next day CAR, wherein short sleep duration and high levels of physical activity resulted in an augmented CAR. Although more sleep clearly predicted a smaller next day CAR in main effect, this study provides additional support that sleep duration effects are also moderated by prior day physical activity. Both behavioral factors should be considered when assessing the CAR and the association between the CAR other psychoneuroendocrine outcomes.

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.

Neuroticism and interpretive bias as risk factors for anxiety and depression.

Neuroticism has been associated with depression and anxiety both cross-sectionally and longitudinally. Interpretive bias has been associated with depression and anxiety, primarily in cross-sectional and bias induction studies. The purpose of the current study was to examine the role of interpretive bias as a prospective risk factor and a mediator of the relation between neuroticism and depressive and anxious symptoms in young adults assessed longitudinally. Neuroticism significantly predicted a broad general distress dimension, but not intermediate fears and anhedonia-apprehension dimensions, nor a narrow social fears dimension. Neuroticism also significantly predicted negative interpretive bias for social scenarios. Negative interpretive bias for social scenarios did not significantly predict dimension scores, nor did it mediate the relation between neuroticism and general distress or social fears. These results suggest that although neuroticism relates to negative interpretive bias, its risk for symptoms of depression and anxiety is at most weakly conferred through negative interpretive bias.

Five-year prospective neuroticism-stress effects on major depressive episodes: Primarily additive effects of the general neuroticism factor and stress.

The past decades of research on predictors of depression have frequently emphasized interactive diathesis-stress questions: What kinds of vulnerabilities under stressful circumstances increase risk of developing depression? This study addresses 3 theoretically important gaps in our knowledge regarding diathesis-stress models of depression: the role of temperament (neuroticism), interactive versus additive effects of neuroticism-stress relationships, and effects of stressor characteristics (acute vs. chronic, major vs. minor events, interpersonal vs. noninterpersonal content). We addressed these gaps in the prediction of major depressive episodes (MDEs) in a sample of high schoolers (n = 559) oversampled for high neuroticism and assessed for presence of MDEs annually for 5 years. Survival analyses provided relatively consistent support for the main effects of the broad vulnerability factor of the general neuroticism factor, acute stressors, and chronic stressors in the prediction of MDEs. In contrast, the majority of our analyses failed to support interactive neuroticism-stress accounts of MDE risk. Integrating our results with the extant literature reinforces the notion that both the general neuroticism factor and stress prospectively predict depressive disorders and highlight that their main effects are significantly larger than their interaction. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

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.

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.

Trait rumination and response to negative evaluative lab-induced stress: neuroendocrine, affective, and cognitive outcomes.

Theoretical models of depression posit that, under stress, elevated trait rumination predicts more pronounced or prolonged negative affective and neuroendocrine responses, and that trait rumination hampers removing irrelevant negative information from working memory. We examined several gaps regarding these models in the context of lab-induced stress. Non-depressed undergraduates completed a rumination questionnaire and either a negative-evaluative Trier Social Stress Test (n = 55) or a non-evaluative control condition (n = 69), followed by a modified Sternberg affective working memory task assessing the extent to which irrelevant negative information can be emptied from working memory. We measured shame, negative and positive affect, and salivary cortisol four times. Multilevel growth curve models showed rumination and stress interactively predicted cortisol reactivity; however, opposite predictions, greater rumination was associated with blunted cortisol reactivity to stress. Elevated trait rumination interacted with stress to predict augmented shame reactivity. Rumination and stress did not significantly interact to predict working memory performance, but under control conditions, rumination predicted greater difficulty updating working memory. Results support a vulnerability-stress model of trait rumination with heightened shame reactivity and cortisol dysregulation rather than hyper-reactivity in non-depressed emerging adults, but we cannot provide evidence that working memory processes are critical immediately following acute stress.

People who need people: Trait loneliness influences positive affect as a function of interpersonal context.

Trait loneliness is associated with negative health consequences; understanding involved processes may elucidate its contributory role. Evolutionary and reaffiliative models associate loneliness with negative affect and dysregulated cortisol responding, while the social monitoring system model associates loneliness with heightened salience of social cues. We hypothesized that loneliness would be associated with greater negative affect and cortisol reactivity, comparing a negative-evaluative audience Trier Social Stress Test ("audience condition;" n = 55) versus a no-audience control condition (n = 69) in non-depressed young adults. Opposing hypotheses, multilevel growth curve models indicated that loneliness was not associated with negative affect or cortisol reactivity in the audience versus no-audience condition. Loneliness was, however, associated with greater positive affect reactivity in the audience versus no-audience condition. In particular, the positive affect subfacet "Interest" was heightened in the audience condition but blunted in the no-audience condition as a function of loneliness, echoing a social monitoring system model of loneliness.

The cortisol reactivity threshold model: Direction of trait rumination and cortisol reactivity association varies with stressor severity.

Various internalizing risk factors predict, in separate studies, both augmented and reduced cortisol responding to lab-induced stress. Stressor severity appears key: We tested whether heightened trait-like internalizing risk (here, trait rumination) predicts heightened cortisol reactivity under modest objective stress, but conversely predicts reduced reactivity under more robust objective stress. Thus, we hypothesized that trait rumination would interact with a curvilinear (quadratic) function of stress severity to predict cortisol reactivity. Evidence comes from 85 currently non-depressed emerging adults who completed either a non-stressful control protocol (n = 29), an intermediate difficulty Trier Social Stress Test (TSST; n = 26), or a robustly stressful negative evaluative TSST (n = 30). Latent growth curve models evaluated relationships between trait rumination and linear and quadratic effects of stressor severity on the change in cortisol and negative affect over time. Among other findings, a significant Trait Rumination x Quadratic Stress Severity interaction effect for cortisol's Quadratic Trend of Time (i.e., reactivity, B = .125, p = .017) supported the hypothesis. Rumination predicted greater cortisol reactivity to intermediate stress (rp = .400, p = .043), but blunted reactivity to more robust negative evaluative stress (rp = -0.379, p = 0.039). Contrasting hypotheses, negative affective reactivity increased independently of rumination as stressor severity increased (B = .453, p = 0.044). The direction of the relationship between an internalizing risk factor (trait rumination) and cortisol reactivity varies as a function of stressor severity. We propose the Cortisol Reactivity Threshold Model, which may help reconcile several divergent reactivity literatures and has implications for internalizing psychopathology, particularly depression.

Depression in early adolescence: Contributions from relational aggression and variation in the oxytocin receptor gene.

Interpersonal stress arising from relational aggression (RA)-the intentional effort to harm others via rejection and exclusion-may increase risk for depression in youth. Biological vulnerabilities related to the hormone oxytocin, which affects social behavior and stress responses, may exacerbate this risk. In a community sample of 307 youth (52% female; age range = 10-14 years), we tested whether (1) the association between RA and subsequent depressive symptoms was mediated through social problems and (2) a single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) moderated this indirect association between RA and depression, where GG homozygotes are predicted to be more sensitive to the effects of social problems than A-allele carriers. Youth-reported RA and depressive symptoms were measured using a structured interview and a questionnaire, respectively. DNA was extracted from saliva collected with Oragene kits. Consistent with the interpersonal theory of depression, the association between relational aggression and subsequent depressive symptoms was mediated by social problems. This indirect effect was further moderated by rs53576 genotype, such that GG homozygotes showed a stronger mediation effect than A-carriers. These results suggest that rs53576 variants confer vulnerability for depression within the context of interpersonal risk factors, such that youth with the GG genotype may be particularly sensitive to the social consequences resulting from RA.

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.