CO2 challenge-evoked hormonal changes predicting TSST changes in cortisol and subjective distress.

The importance of stressor response in relation to the development of psychopathology has been recognized for decades, yet the relationship is not fully understood. The Trier Social Stress Test (TSST) is an established conditioned stressor and frequently used to assess cortisol response to acute stress in different psychopathologies. The 35 % CO2 Challenge is a biological stressor and has mostly been utilized to assess subjective responses in anxiety related disorders. In the current study (N=189), we assessed the hormonal effects (cortisol, testosterone) and subjective distress (stress, anxiety, and fear) of the 35 % CO2 Challenge, and several days later, assessed the hormonal and subjective distress effects of the TSST in a mixed-sex, college-aged sample, to test for predictive effects of the 35 % CO2 Challenge on TSST-evoked outcomes. No testosterone by cortisol interaction effects were found in females. In males, the 35 % CO2 Challenge-evoked interaction of testosterone and cortisol predicted TSST-evoked subjective stress, anxiety, and fear, with higher concentrations of testosterone predicting subjective distress, but only at (relatively) low concentrations of cortisol (one standard deviation below mean concentrations). This result - in line with the dual-hormone hypothesis - suggests the 35 % CO2 Challenge could be utilized in a wider array of laboratory stress response research.

A dual-system, machine-learning approach reveals how daily pubertal hormones relate to psychological well-being in everyday life.

The two studies presented in this paper seek to resolve mixed findings in research linking activity of pubertal hormones to daily adolescent outcomes. In study 1 we used a series of Confirmatory Factor Analyses to compare the fit of one and two-factor models of seven steroid hormones (n = 994 participants, 8084 samples) of the HPA and HPG axes, using data from a field study (https://www.icpsr.umich.edu/web/ICPSR/studies/38180) collected over ten consecutive weekdays in a representative sample of teens starting high school. In study 2, we fit a Bayesian model to our large dataset to explore how hormone activity was related to outcomes that have been demonstrated to be linked to mental health and wellbeing (self-reports of daily affect and stress coping). Results reveal, first that a two-factor solution of adolescent hormones showed good fit to our data, and second, that HPG activity, rather than the more often examined HPA activity, was associated with improved daily affect ratios and stress coping. These findings suggest that field research, when it is combined with powerful statistical techniques, may help to improve our understanding of the relationship between adolescent hormones and daily measures of well-being.

Chemiluminescent immunoassay overestimates hormone concentrations and obscures testosterone sex differences relative to LC-MS/MS in a field study of diverse adolescents.

Background: Methodological comparisons of hormone quantification techniques have repeatedly demonstrated that, in adults, enzyme immunoassay (EIA) inflates steroid hormone concentrations relative to mass spectrometry. However, methodological comparisons in adolescent samples remain rare, and few studies have examined how chemiluminescent immunoassay (CLIA), another popular immunoassay, compares to mass spectrometry. Additionally, no studies have examined how differences in analytical techniques may be affecting relationships between steroid hormone levels and outcomes of interest, such as psychopathology. This pre-registered analysis of an existing dataset measured salivary cortisol and testosterone using both CLIA and liquid chromatography dual mass spectrometry (LC-MS/MS) in a repeated measures (516 samples) sample of 207 9th graders. Methods: In aim 1, this study sought to expand on past findings by 1) measuring inflation of testosterone and cortisol by CLIA in a relatively large adolescent sample, and 2) showing that CLIA (like EIA) testosterone inflation was especially true in groups with low 'true' testosterone levels. In aim 2, this study sought to examine the impact of hormone quantification method on relationships between hormone levels and psychopathological measures (the Children's Depression Inventory, the Perceived Social Stress Scale, the UCLA Loneliness Scale, and the Anxious Avoidant and Negative Self Evaluation subscales of the Social Anxiety Scale for Adolescents). Results: We found that CLIA, like EIA, inflated testosterone and cortisol levels and overestimated female testosterone resulting in suppressed sex differences in testosterone. We did not observe these same patterns when examining testosterone in individuals with differing levels of pubertal development. Results of psychopathology analyses demonstrated no significant method differences in hormone-psychopathology relationships. Conclusions: Our findings show that CLIA introduces proportional bias in cortisol and testosterone in a manner that suppresses sex differences in testosterone. Steroid measurement method did not significantly moderate the relationship between hormones and psychopathology in our sample, though more work is needed to investigate this question in larger, clinical samples.

Trait attributions and threat appraisals explain why an entity theory of personality predicts greater internalizing symptoms during adolescence.

Adolescents who hold an entity theory of personality - the belief that people cannot change - are more likely to report internalizing symptoms during the socially stressful transition to high school. It has been puzzling, however, why a cognitive belief about the potential for change predicts symptoms of an affective disorder. The present research integrated three models - implicit theories, hopelessness theories of depression, and the biopsychosocial model of challenge and threat - to shed light on this issue. Study 1 replicated the link between an entity theory and internalizing symptoms by synthesizing multiple datasets (N = 6,910). Study 2 examined potential mechanisms underlying this link using 8-month longitudinal data and 10-day diary reports during the stressful first year of high school (N = 533, 3,199 daily reports). The results showed that an entity theory of personality predicted increases in internalizing symptoms through tendencies to make fixed trait causal attributions about the self and maladaptive (i.e., "threat") stress appraisals. The findings support an integrative model whereby situation-general beliefs accumulate negative consequences for psychopathology via situation-specific attributions and appraisals.

Gonadal and adrenal hormones interact with pubertal maturation to predict depressive symptoms in a group of high-school females.

Adolescent females are at elevated risk for the development of depression. In this study, we addressed two questions: Are pubertal hormones associated with adolescent mental health? Might this association depend on pubertal development? We tested the hypothesis that estradiol, which has been associated with adolescent social sensitivity, might interact with pubertal stage to predict depression risk at three time points in ninth and tenth grade. Hormones and pubertal development were measured ninth-grade females. Linear regression analyses were used to predict fall ninth-grade (N = 79), spring ninth-grade (N = 76), and spring tenth-grade (N = 67) Children's Depression Inventory (CDI) scores. The hypothesized model was not statistically significant, but exploratory analyses revealed that two- and three-way interactions incorporating estradiol, puberty (stage and perceived onset), and cortisol predicted current and future CDI scores. Our exploratory model did not predict changes in CDI but did account for future (spring of ninth grade) CDI scores. Specifically, estradiol was positively correlated with fall and spring ninth-grade depressive symptoms in participants with high cortisol who also reported earlier stages and later perceived onset of pubertal development. These findings suggest that hormones associated with sensitivity to the social environment deserve consideration in models of adolescent depression risk.

Factors predicting the development of psychopathology among first responders: A prospective, longitudinal study.

Objective: Previous research has shown that first responders exhibit elevated rates of psychopathology. Factors predicting the development of this psychopathology, however, remain understudied. This study longitudinally examined predictors of posttraumatic stress disorder (PTSD), depression, and anxiety symptoms in first responders. Method: Participants included 135 emergency medical service (EMS) providers. Multiple linear regressions were used to model predictors of change in PTSD, depression, and anxiety symptomatology from baseline to 3-month follow-up. Baseline levels of social support, sleep, emotional stability, and perceived stress were examined as potential predictors. Results: Results revealed that (a) increases in PTSD symptoms, (b) increases in depression symptoms, and (c) increases in anxiety symptoms at 3-month follow-up were each predicted by worse sleep and lower social support at baseline. In particular, the sleep subscale of disturbed sleep and the social support subscale of appraisal appeared to be driving these effects. Conclusion: These results highlight the importance of social support and sleep hygiene in protecting against increases in psychopathology symptoms in EMS providers, and set the stage for future interventions to target sleep disturbances and encourage deeper social connections in order to foster resilience in first responders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Getting Fewer "Likes" Than Others on Social Media Elicits Emotional Distress Among Victimized Adolescents.

Three studies examined the effects of receiving fewer signs of positive feedback than others on social media. In Study 1, adolescents (N = 613, Mage  = 14.3 years) who were randomly assigned to receive few (vs. many) likes during a standardized social media interaction felt more strongly rejected, and reported more negative affect and more negative thoughts about themselves. In Study 2 (N = 145), negative responses to receiving fewer likes were associated with greater depressive symptoms reported day-to-day and at the end of the school year. Study 3 (N = 579) replicated Study 1's main effect of receiving fewer likes and showed that adolescents who already experienced peer victimization at school were the most vulnerable. The findings raise the possibility that technology which makes it easier for adolescents to compare their social status online-even when there is no chance to share explicitly negative comments-could be a risk factor that accelerates the onset of internalizing symptoms among vulnerable youth.

Exogenous testosterone increases sensitivity to moral norms in moral dilemma judgements.

Moral dilemma judgements frequently involve decisions where moral norms and the greater good are in conflict. The current preregistered study tested the effect of the steroid hormone testosterone on moral dilemma judgements using a double-blind administration of testosterone or placebo. Counter to predictions, testosterone administration led to increased inaction in moral dilemmas where harmful actions prohibited by moral norms increase overall well-being. Using a mathematical model to disentangle sensitivity to consequences, sensitivity to moral norms and general preference for inaction versus action, analyses further revealed that testosterone administration influenced judgements by increasing sensitivity to moral norms. Exploratory analyses suggested the opposite pattern for endogenous testosterone measured at baseline, in that higher levels of endogenous testosterone were associated with lower sensitivity to moral norms. The results indicate that the role of testosterone in moral judgements is more complex than suggested by previous findings. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 13 November 2017. The protocol, as accepted by the journal, can be found at https://osf.io/rysbe/ 1.

An Entity Theory of Intelligence Predicts Higher Cortisol Levels When High School Grades Are Declining.

Grades often decline during the high school transition, creating stress. The present research integrates the biopsychosocial model of challenge and threat with the implicit theories model to understand who shows maladaptive stress responses. A diary study measured declines in grades in the first few months of high school: salivary cortisol (N = 360 students, N = 3,045 observations) and daily stress appraisals (N = 499 students, N = 3,854 observations). Students who reported an entity theory of intelligence (i.e., the belief that intelligence is fixed) showed higher cortisol when grades were declining. Moreover, daily academic stressors showed a different lingering effect on the next day's cortisol for those with different implicit theories. Findings support a process model through which beliefs affect biological stress responses during difficult adolescent transitions.

Cortisol, Testosterone, and Prospective Risk for War-zone Stress-Evoked Depression.

Introduction: The major challenges of efforts to reveal biological risk factors and biomarkers of depression include the complexity of underlying systems, interactions with other systems, and contextual factors governing their expression. Altered endocrine function is believed to be a central contributor to depressive illness, but across studies, evidence for a link between endocrine markers and depression has been mixed, inconclusive, or conditional in nature. In the present study, we evaluated basal testosterone (T), cortisol (C), and CO2 inhalation-stress-reactivity measures of these hormones (TR, CR) as pre-deployment moderators of the later impact of war-zone stressors on depression symptoms in-theater. Materials and Methods: At pre-deployment, U.S. soldiers (N = 120) completed demographic, clinical and hormone measures, and during deployment, they completed monthly, web-based assessments of war-zone stressors and depression symptoms (N = 533 observations). Mixed effects models estimated the effects of the pre-deployment hormone profiles in moderating war-zone stressors' impact on in-theater depression. Models also tested whether hormonally linked risk for later stress-evoked depression depends on pre-existing depression. Results: Controlling for pre-deployment depression, high T was protective; whereas TR had depressogenic effects that were amplified by pre-deployment depression. Further, high C was protective, but heightened CR was depressogenic, but only among those with elevated pre-deployment depression. Conclusions: Findings highlight the importance of examining basal and reactivity measures of endocrine function, and use of prospective, longitudinal models to test hypothesized causal pathways associated with depression vulnerability in the war-zone. Results also suggest that pre-existing depression and cortisol may work in tandem to increase vulnerability for later stress-evoked depression in the war-zone.

Hormonal underpinnings of status conflict: Testosterone and cortisol are related to decisions and satisfaction in the hawk-dove game.

A contribution to a special issue on Hormones and Human Competition.Testosterone is theorized to influence status-seeking behaviors such as social dominance and competitive behavior, but supporting evidence is mixed. The present study tested the roles of testosterone and cortisol in the hawk-dove game, a dyadic economic decision-making paradigm in which earnings depend on one's own and the other player's choices. If one person selects the hawk strategy and the other person selects the dove strategy, the player who selected hawk attains a greater financial pay-off (status differentiation). The worst financial outcome occurs when both players choose the hawk strategy (status confrontation). Ninety-eight undergraduate students (42 men) provided saliva samples and played ten rounds of the hawk-dove game with another same-sex participant. In support of the hypothesis that testosterone is related to status concern, individuals higher in basal testosterone made more hawk decisions - decisions that harmed the other player. Acute decreases in cortisol were also associated with more hawk decisions. There was some empirical support for the dual-hormone hypothesis as well: basal testosterone was positively related to satisfaction in the game among low basal-cortisol individuals but not among high basal-cortisol individuals. There were no significant sex differences in these hormonal effects. The present findings align with theories of hormones and status-seeking behavior at the individual level, but they also open up new avenues for research on hormone profiles at the collective level. Our results suggest that the presence of two or more high-testosterone members increases the likelihood of status confrontations over a limited resource that can undermine collective outcomes.

Dual-hormone stress reactivity predicts downstream war-zone stress-evoked PTSD.

BACKGROUND: The crucial role of the hypothalamic-pituitary-adrenal axis (HPA) in stress-related homeostasis suggests dysregulated HPA involvement in the pathogenesis of post-traumatic stress disorder (PTSD), yet most studies examining linkages between HPA axis measures and PTSD have yielded null findings. One untested explanation for this inconsistency is a failure to account for simultaneous adrenal and gonadal influence. Here we tested the singular and interactive effects of cortisol (CR) and testosterone (TR) reactivity as moderators of war-zone stress evoked PTSD emergence in the war-zone. METHODS: U.S. soldiers (N=120) scheduled for deployment to Iraq completed pre-deployment measures of CR and TR stress reactivity to a CO2 inhalation challenge. Once deployed, monthly assessments of exposure to traumatic war-zone stressors and PTSD symptoms were collected via a web-based assessment system. RESULTS: Cortisol hypo-reactivity potentiated the pathogenic impact of war-zone stressors only in soldiers for whom the CO2 challenge did not elevate testosterone, suggesting that the dual hormone stress reactivity profile of blunted cortisol and testosterone may confer increased risk for PTSD emergence by potentiating the pathogenic effects of war-zone stressors. CONCLUSIONS: Findings underscore the utility of assessing both HPA and HPG stress reactivity when assessing PTSD vulnerability and may help inform efforts for enhanced soldier screening and inoculation to war-zone stressors.

Sex differences in cortisol's regulation of affiliative behavior.

A contribution to a special issue on Hormones and Human Competition. A stress perspective is used to illuminate how competitive defeat and victory shape biology and behavior. We report a field study examining how change in cortisol following perceived defeat (vs. victory) in a competition-in this case, a dog agility competition-relates to affiliative behavior. Following competition, we measured cortisol change and the extent to which dog handlers directed affiliative behaviors toward their dogs. We found striking sex differences in affiliation. First, men were more affiliative toward their dogs after victory, whereas women were more affiliative after defeat. Second, the greater a female competitor's increase in cortisol, the more time she spent affiliating with her dog, whereas for men, the pattern was the exact opposite: the greater a male competitor's increase in cortisol, the less time he spent affiliating with his dog. This pattern suggests that, in the wake of competition, men and women's affiliative behavior may serve different functions-shared celebration for men; shared consolation for women. These sex differences show not only that men and women react very differently to victory and defeat, but also that equivalent changes in cortisol across the sexes are associated with strikingly different behavioral consequences for men and women.

The interaction of testosterone and cortisol is associated with attained status in male executives.

Are hormone levels associated with the attainment of social status? Although endogenous testosterone predicts status-seeking social behaviors, research suggests that the stress hormone cortisol may inhibit testosterone's effects. Thus, individuals with both high testosterone and low cortisol may be especially likely to occupy high-status positions in social hierarchies while individuals with high testosterone and high cortisol may not. We tested this hypothesis by recruiting a sample of real executives and examining testosterone, cortisol, and a concrete indicator of attained status: the number of subordinates over which the executive has authority. Despite the myriad nonhormonal factors that determine organizational promotion, the executives' endogenous testosterone and cortisol interacted to significantly predict hierarchical position: Testosterone positively predicted executives' number of subordinates, but only among low-cortisol executives. The results imply that reducing cortisol levels via stress reduction may be a critical goal not only because doing so will improve health but also because doing so may enhance leadership potential. (PsycINFO Database Record

Hormones and ethics: Understanding the biological basis of unethical conduct.

Globally, fraud has been rising sharply over the last decade, with current estimates placing financial losses at greater than $3.7 trillion annually. Unfortunately, fraud prevention has been stymied by lack of a clear and comprehensive understanding of its underlying causes and mechanisms. In this paper, we focus on an important but neglected topic--the biological antecedents and consequences of unethical conduct--using salivary collection of hormones (testosterone and cortisol). We hypothesized that preperformance cortisol levels would interact with preperformance levels of testosterone to regulate cheating behavior in 2 studies. Further, based on the previously untested cheating-as-stress-reduction hypothesis, we predicted a dose-response relationship between cheating and reductions in cortisol and negative affect. Taken together, this research marks the first foray into the possibility that endocrine-system activity plays an important role in the regulation of unethical behavior.

Estradiol and cortisol interactions in youth externalizing psychopathology.

Growing evidence has indicated that gonadal and stress hormones interact to shape socially dominant behavior and externalizing psychopathology; however, such work to date has focused exclusively on the testosterone-cortisol interaction, despite expectations that estradiol should be associated with similar behavioral outcomes to testosterone. Here, we present the first empirical test of the hypothesis that adolescent males and females (N=105, ages 13-18) with high estradiol and low cortisol concentrations are at highest risk for externalizing problems, but - replicating previous work - only among adolescents high on pathological personality traits. Parents reported on youth psychopathology and personality, and hormone concentrations were measured via passive drool. Results confirmed the hypothesis: high estradiol was associated with more externalizing behaviors, but only when cortisol was low and personality traits of disagreeableness and emotional instability were high. Further, these associations held when controlling for testosterone concentrations. These findings provide the first empirical evidence of a hypothalamic pituitary adrenal (HPA)×hypothalamic pituitary gonadal (HPG) axis interaction that extends the "dual hormone" hypothesis beyond testosterone.

Personality × hormone interactions in adolescent externalizing psychopathology.

The "dual-hormone" hypothesis predicts that testosterone and cortisol will jointly regulate aggressive and socially dominant behavior in children and adults (e.g., Mehta & Josephs, 2010). The present study extends research on the dual-hormone hypothesis by testing the interaction between testosterone, cortisol, and personality disorder (PD) traits in predicting externalizing problems in a community sample of adolescent males and females. Participants were 106 youth from the community, ranging in age from 13-18 (Mage = 16.01 years, SDage = 1.29), and their parents. Parents and youth provided ratings on an omnibus measure of personality pathology and externalizing problems. Youth provided saliva samples via passive drool from which testosterone and cortisol levels were obtained. Robust moderation of the joint effects of testosterone and cortisol on parent-reported externalizing problems was found for both higher-order PD traits associated with externalizing psychopathology (Disagreeableness and Emotional Instability). Higher testosterone was associated with externalizing outcomes, but only when cortisol was low, and only among youth with high levels of Disagreeableness and Emotional Instability. These findings provide the first evidence for the dual-hormone hypothesis in a mixed-sex sample of community adolescents, but importantly offer novel evidence for the importance of personality traits. Examination of the joint regulation of externalizing problems by testosterone and cortisol in the context of adolescent personality may help to clarify inconsistent main effects of testosterone and cortisol on clinical externalizing phenotypes.

Hormones: empirical contribution. Cortisol reactivity and recovery in the context of adolescent personality disorder.

The present study examined whether the associations between stress responses and psychopathology were moderated by adolescent personality disorder (PD) traits. Participants were a community sample of 106 adolescents (47 male, Mage = 16.01) and their parents. Parents reported on adolescents' PD traits and behavioral problems. Changes in salivary cortisol were assessed in response to a laboratory-based stress induction. Moderated regression analyses revealed significant linear and quadratic interactions between cortisol recovery and PD traits in the prediction of behavioral problems. Although typically conceptualized as "adaptive," steeper poststressor recovery was associated with more behavioral problems when PD traits were high. These findings suggest that, in the presence of maladaptive personality traits, premature recovery from environmental stressors may indicate an inability to respond appropriately to negative environmental stimuli, thus reflecting a core disturbance in PD trait functioning. The results underscore the informative role that personality plays in illuminating the nature of hormone functioning in adolescents and are interpreted in a developmental psychopathology framework.

Endogenous testosterone levels are associated with assessments of unfavourable health information.

The purpose of this study was to investigate whether participants' assessments of unfavourable health information are associated with individual differences in basal testosterone. Testosterone has previously been related to assessments of threat in social and other domains. 52 undergraduate males were tested for a minor, fictitious medical condition thioamine acetylase deficiency ('TAA deficiency') in a paradigm that was developed to examine the thoughts and behaviours of individuals who have just received unfavourable medical news. In a variation on the classic paradigm, all participants were told that they had 'TAA deficiency,' after which they rated the seriousness and prevalence of that condition as well as 19 other actual conditions. Higher testosterone levels were significantly correlated with lower estimates of both the seriousness and prevalence of TAA deficiency as well as lower median seriousness and prevalence estimates of the 19 actual conditions. Findings are discussed in light of current research in the field of behavioural endocrinology. This study provides preliminary evidence that individual differences in assessments of threatening health information may be associated with neurobiological characteristics.

Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction.

BACKGROUND: Striking parallels are observed when comparing the literature on the 5-HTTLPR of the serotonin transporter gene (SLC6A4) to the testosterone (T) literature on measures of stress reactivity and neural activity. Short (S) allele carriers and individuals higher in testosterone levels show exaggerated stress responses, amygdala hyperactivity, and reduction of amygdala-prefrontal cortex coupling when exposed to threat. METHODS: Three studies tested the hypothesis that higher T, S carriers would show increased cortisol responses to threat. RESULTS: Supporting the hypothesis, a T × 5-HTTLPR interaction was obtained across all studies. Threats to status via social exclusion (Study 1), cognitive/perceptual failure (Study 2), and physical competence (Study 3) all produced elevated cortisol levels in S carriers with higher T levels. An unexpected result was that 5-HTTLPR long (L) allele homozygotes with higher T showed lower cortisol levels in response to threat-a pattern of response that closely parallels that reported for psychopathic individuals. Finally, combining effect sizes across studies showed that the likelihood that these effects were due to Type 1 errors was quite low. CONCLUSIONS: What emerges from these studies is a novel yet reliable, and synergistic relationship between 5-HTTLPR genotype and testosterone on stress reactivity, possibly conferring vulnerability for multiple neuropsychiatric disorders.