Dampened psychobiological responses to stress and substance use in adolescence.

Substance use increases throughout adolescence, and earlier substance use may increase risk for poorer health. However, limited research has examined whether stress responses relate to adolescent substance use, especially among adolescents from ethnic minority and high-adversity backgrounds. The present study assessed whether blunted emotional and cortisol responses to stress at age 14 related to substance use by ages 14 and 16, and whether associations varied by poverty status and sex. A sample of 277 Mexican-origin youth (53.19% female; 68.35% below the poverty line) completed a social-evaluative stress task, which was culturally adapted for this population, and provided saliva samples and rated their anger, sadness, and happiness throughout the task. They also reported whether they had ever used alcohol, marijuana, cigarettes, and vaping of nicotine at age 14 and again at age 16. Multilevel models suggested that blunted cortisol reactivity to stress was associated with alcohol use by age 14 and vaping nicotine by age 16 among youth above the poverty line. Also, blunted sadness and happiness reactivity to stress was associated with use of marijuana and alcohol among female adolescents. Blunted stress responses may be a risk factor for substance use among youth above the poverty line and female adolescents.

Testosterone and hippocampal trajectories mediate relationship of poverty to emotion dysregulation and depression.

There is robust evidence that early poverty is associated with poor developmental outcomes, including impaired emotion regulation and depression. However, the specific mechanisms that mediate this risk are less clear. Here we test the hypothesis that one pathway involves hormone mechanisms (testosterone and DHEA) that contribute to disruption of hippocampal brain development, which in turn contributes to perturbed emotion regulation and subsequent risk for depression. To do so, we used data from 167 children participating in the Preschool Depression Study, a longitudinal study that followed children from preschool (ages 3 to 5 y) to late adolescence, and which includes prospective assessments of poverty in preschool, measures of testosterone, DHEA, and hippocampal volume across school age and adolescence, and measures of emotion regulation and depression in adolescence. Using multilevel modeling and linear regression, we found that early poverty predicted shallower increases of testosterone, but not DHEA, across development, which in turn predicted shallower trajectories of hippocampal development. Further, we found that early poverty predicted both impaired emotion regulation and depression. The relationship between early poverty and self-reported depression in adolescence was explained by serial mediation through testosterone to hippocampus to emotion dysregulation. There were no significant interactions with sex. These results provide evidence about a hormonal pathway by which early poverty may contribute to disrupted brain development and risk for mental health problems later in life. Identification of such pathways provide evidence for potential points of intervention that might help mitigate the impact of early adversity on brain development.

Longitudinal patterns of neuroendocrine coupling from middle childhood to early adolescence.

Recent scholarship has highlighted the importance of understanding relations between hormones, rather than studying hormones in isolation. Considering neuroendocrine coupling, or the coordination of hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-gonadal axis hormones over time, is one way to investigate how systems governing stress responsiveness and pubertal development covary during critical periods. To date, however, most work has considered hormone coupling cross-sectionally. The current study investigated neuroendocrine coupling in a longitudinal sample from the Northeastern United States. Youth (N = 437, 53% male, 90% White) provided saliva samples for analysis of diurnal hormone activity at ages 9 (three samples per day across 3 days) and 12 (one sample per day on the same weekday for 4 weeks). At both timepoints, samples collected 30-min after waking were assayed for cortisol, dehydroepiandrosterone (DHEA), and testosterone. Multilevel growth modeling was used to determine how levels of morning cortisol changed in tandem with DHEA and testosterone. Morning cortisol-DHEA coupling varied by child sex, as males' cortisol-DHEA diminished over time, especially among pubertally advanced males. Females, in contrast, demonstrated strengthening cortisol-DHEA coupling over time, especially more pubertally advanced females. Morning cortisol-testosterone coupling did not vary by sex or pubertal status, demonstrating strengthening associations between ages 9 and 12. The current findings contribute to the literature on hormone coupling across development and expand this work into an earlier developmental phase than previously investigated.

The codevelopment of adolescents' and parents' anxiety and depression: Moderating influences of youth gender and psychophysiology.

METHODS: In a 2-year longitudinal study of 220 families, we examined how youth gender and adrenocortical and parasympathetic activity moderated reciprocal, bidirectional relations between parent and youth anxiety and depression problems. RESULTS: Maternal anxiety predicted subsequent youth anxiety and depression. Maternal depression predicted youth anxiety and, for daughters and youth with low adrenocortical reactivity, youth depression. Youth depression predicted maternal depression only for youth with high adrenocortical reactivity. There were no associations between paternal and youth psychopathology. DISCUSSION: Examining youth gender and psychophysiological characteristics that shape the nature of bidirectional influences may inform efforts to identify families at heightened risk for intergenerational transmission of psychopathology.

Longitudinal effects of family psychopathology and stress on pubertal maturation and hormone coupling in adolescent twins.

Adolescents experience profound neuroendocrine changes, including hormone "coupling" between cortisol, testosterone, and dehydroepiandrosterone. Emerging research has only begun to elucidate the role of hormone coupling, its genetic and environmental etiology, and the extent to which coupling is impacted by gender, puberty, and family context. We included measures on parent and child mental health, parenting stress, and family conflict of 444 twin pairs and their parents across two timepoints, when youth were on average 8 and 13 years old, respectively. Structural equation models examined the impact of family context effects on coupling during adolescence. Biometric twin models were then used to probe additive genetic, shared, and non-shared environmental effects on hormone coupling. Hormones were more tightly coupled for females than males, and coupling was sensitive to parental depression and co-twin psychopathology symptoms and stress exposure in females. The association between family context and coupling varied across specific neuroendocrine measures and was largely distinct from pubertal maturation. Biometric models revealed robust shared and non-shared environmental influences on coupling. We found that family antecedents modify the strength of coupling. Environmental influences account for much of the variation on coupling during puberty. Gender differences were found in genetic influences on coupling.

Adrenocortical and autonomic attunement between romantic partners in emerging adulthood.

Parent-child physiological attunement, particularly during stressful situations, appears adaptive as shared stress reactivity may promote dyadic engagement. Romantic partners eventually replace parents as the primary support figure, yet it remains unclear whether romantic partners buffer physiological stress or display physiological attunement as most studies on adults examine attunement during conflict paradigms. The present study examined physiological attunement in 63 emerging adult romantic partner dyads (one partner was the active participant, the other the observer) during the Trier Social Stress Task (TSST). Heart rate (HR) and respiratory sinus arrhythmia (RSA) were continuously monitored across the visit. Repeated saliva samples were assayed for cortisol. Physiological attunement was operationalized as a correlation in biomarkers between the TSST participant and their partner; sex, social support, and physical proximity were examined as moderators. We then compared the biomarker profiles of partnered-TSST participants to individuals who participated in the TSST solo (n = 63) to determine if partner presence buffered stress biomarker reactivity during the TSST. RSA attunement between partners was found but was not further moderated by social support or sex. Adrenocortical attunement was moderated, such that lower social support and increased proximity resulted in higher attunement. HR attunement was higher when the participant was male and when partners were in close physical proximity. Compared to TSST solo, romantic partner presence increased participant cortisol levels and altered HR reactivity, suggesting that emerging adult romantic partners do not buffer physiological stress reactivity. Future research should examine whether physiological attunement and partner presence is protective in more established relationships.

Next Steps in Puberty Research: Broadening the Lens Toward Understudied Populations.

Decades of puberty research have yielded key scientific discoveries. Building on the field's rich history, we highlight four understudied populations: youth of color, boys, sexual minority youth, and gender minority youth. We explore why scientific study has been slow to evolve in these groups and propose paths forward for exciting new work. For ethnically racially diverse youth, we discuss the need to incorporate culture and context. For boys, we highlight methodological issues and challenges of mapping existing conceptual models onto boys. For sexual and gender minority youth, we discuss unique challenges during puberty and suggest ways to better capture their experiences. With an eye toward a new era, we make recommendations for next steps and underscore the importance of transdisciplinary research.

Callous-unemotional traits and early life stress predict treatment effects on stress and sex hormone functioning in incarcerated male adolescents.

The stress response system is highly plastic, and hormone rhythms may "adaptively calibrate" in response to treatment. This investigation assessed whether stress and sex hormone diurnal rhythms changed over the course of behavioral treatment, and whether callous-unemotional (CU) traits and history of early adversity affected treatment results on diurnal hormone functioning in a sample of 28 incarcerated adolescent males. It was hypothesized that the treatment would have beneficial effects, such that healthier diurnal rhythms would emerge post-treatment. Diurnal cortisol, testosterone, and dehydroepiandrosterone (DHEA) were sampled two weeks after admission to the correctional/treatment facility, and again approximately four months later. Positive treatment effects were detected for the whole sample, such that testosterone dampened across treatment. CU traits predicted a non-optimal hormone response to treatment, potentially indicating biological preparedness to respond to acts of social dominance and aggression. The interaction between CU traits and adversity predicted a promising and sensitized response to treatment including increased cortisol and a steeper testosterone drop across treatment. Results suggest that stress and sex hormones are highly receptive to treatment during this window of development.

The role of bicultural adaptation, familism, and family conflict in Mexican American adolescents' cortisol reactivity.

Scarce research has examined stress responsivity among Latino youths, and no studies have focused on the role of acculturation in shaping cortisol stress response in this population. This study assessed Mexican American adolescents' Mexican and Anglo cultural orientations and examined prospective associations between their patterns of bicultural orientation and hypothalamic-pituitary-adrenal cortisol reactivity to an adapted Trier Social Stress Test. The sample included 264 youths from a longitudinal birth cohort study who completed the Trier Social Stress Test and provided saliva samples at age 14. The youths completed assessments of cultural orientation at age 12, and family conflict and familism at age 14. Analyses testing the interactive effects of Anglo and Mexican orientation showed significant associations with cortisol responsivity, including the reactivity slope, peak levels, and recovery, but these associations were not mediated by family conflict nor familism values. Findings revealed that bicultural youth (high on both Anglo and Mexican orientations) showed an expected pattern of high cortisol responsivity, which may be adaptive in the context of a strong acute stressor, whereas individuals endorsing only high levels of Anglo orientation had a blunted cortisol response. Findings are discussed in relation to research on biculturalism and the trade-offs and potential recalibration of a contextually responsive hypothalamic-pituitary-adrenal axis for acculturating adolescents.

Social evaluative threat with verbal performance feedback alters neuroendocrine response to stress.

Laboratory stress tasks such as the Trier Social Stress Test (TSST) have provided a key piece to the puzzle for how psychosocial stress impacts the hypothalamic-pituitary-adrenal axis, other stress-responsive biomarkers, and ultimately wellbeing. These tasks are thought to work through biopsychosocial processes, specifically social evaluative threat and the uncontrollability heighten situational demands. The present study integrated an experimental modification to the design of the TSST to probe whether additional social evaluative threat, via negative verbal feedback about speech performance, can further alter stress reactivity in 63 men and women. This TSST study confirmed previous findings related to stress reactivity and stress recovery but extended this literature in several ways. First, we showed that additional social evaluative threat components, mid-task following the speech portion of the TSST, were still capable of enhancing the psychosocial stressor. Second, we considered stress-reactive hormones beyond cortisol to include dehydroepiandrosterone (DHEA) and testosterone, and found these hormones were also stress-responsive, and their release was coupled with one another. Third, we explored whether gain- and loss-framing incentive instructions, meant to influence performance motivation by enhancing the personal relevance of task performance, impacted hormonal reactivity. Results showed that each hormone was stress reactive and further had different responses to the modified TSST compared to the original TSST. Beyond the utility of showing how the TSST can be modified with heightened social evaluative threat and incentive-framing instructions, this study informs about how these three stress-responsive hormones have differential responses to the demands of a challenge and a stressor.

Positive parenting predicts cortisol functioning six years later in young adults.

Research which indicates that adverse experiences influence hypothalamic-pituitary-adrenal (HPA) axis functioning illustrates the social environment 'getting under the skin'. The present study extended this literature by examining whether positive social forces within the caregiving environment can also impact cortisol functioning. We conducted a prospective investigation of over 300 youth, half of whom were White and half were Black. Attachment, bonding and parental rewards for positive behaviors were observed or reported by the youth as an 8th grader. Twelve repeated measures of salivary cortisol were examined six years later when youth were young adults (mean age 20). Race differences were explored. Stronger attachment, bonding and teen-reported positive parenting were predictive of high waking cortisol and steeper diurnal slopes six years later. This effect was nonlinear and additive, such that youth whose social contexts were characterized by the strongest attachment, bonding and rewarding parental relationships had the highest waking cortisol. When effects were moderated by race, findings were such that links of positive parenting with HPA functioning were more consistent for White than Black youth. Findings suggest that positive aspects of the caregiving environment can also 'get under the skin' and these effects are additive across a range of caregiving indices. These findings dovetail with an emerging literature on the powerful role of social support for shaping the body's stress response system and are interpreted as consistent with the Adaptive Calibration Model which suggests that cortisol regulation can have adaptive significance. A video abstract of this article can be viewed at: https://youtu.be/8evHXpt_TXM.

Hypothalamic-Pituitary-Adrenal Reactivity to Acute Stress: an Investigation into the Roles of Perceived Stress and Family Resources.

Rurally situated African Americans suffer from chronic exposure to stress that may have a deleterious effect on health outcomes. Unfortunately, research on potential mechanisms that underlie health disparities affecting the African American community has received limited focus in the scientific literature. This study investigated the relationship between perceived stress, family resources, and cortisol reactivity to acute stress. A rural sample of African American emerging adults (N = 60) completed a battery of assessments, the Trier Social Stress Test (TSST), and provided four samples of salivary cortisol: prior to receiving TSST instructions, prior to conducting the speech task, immediately following the TSST, and 15-20 min following the TSST. As predicted, cortisol levels increased in response to a controlled laboratory inducement of acute stress. Moreover, diminished levels of family resources were associated with blunted cortisol reactivity to acute stress. Of note, higher levels of perceived stress over the past month and being male were independently associated with lower levels of cortisol at baseline. Lack of family resources had a blunting relationship on the hypothalamic-pituitary-adrenal axis reactivity. These findings provide biomarker support for the relationship between family resources-an indicator associated with social determinants of health-and stress physiology within a controlled laboratory experiment. Identifying mechanisms that work toward explanation of within-group differences in African American health disparities is both needed and informative for culturally informed prevention and intervention efforts.

Genetic and Environmental Contributions to Covariation Between DHEA and Testosterone in Adolescent Twins.

Although several studies have shown that pubertal tempo and timing are shaped by genetic and environmental factors, few studies consider to what extent endocrine triggers of puberty are shaped by genetic and environmental factors. Doing so moves the field from examining correlated developmentally-sensitive biomarkers toward understanding what drives those associations. Two puberty related hormones, dehydroepiandrosterone and testosterone, were assayed from salivary samples in 118 MZ (62 % female), 111 same sex DZ (46 % female) and 103 opposite-sex DZ twin pairs, aged 12-16 years (M = 13.1, SD = 1.3). Pubertal status was assessed with a composite of mother- and self-reports. We used biometric models to estimate the genetic and environmental influences on the variance and covariance in testosterone and DHEA, with and without controlling for their association with puberty, and to test for sex differences. In males, the variance in testosterone and pubertal status was due to shared and non-shared environmental factors; variation in DHEA was due to genetic and non-shared environmental factors. In females, variance in testosterone was due to genetic and non-shared environmental factors; genetic, shared, and non-shared environmental factors contributed equally to variation in DHEA. In males, the testosterone-DHEA covariance was primarily due to shared environmental factors that overlapped with puberty as well as shared and non-shared environmental covariation specific to testosterone and DHEA. In females, the testosterone-DHEA covariance was due to genetic factors overlapping with pubertal status, and shared and non-shared environmental covariation specific to testosterone and DHEA.

The association between affective psychopathic traits, time incarcerated, and cortisol response to psychosocial stress.

Previous research has demonstrated that psychopathic personality traits are significantly predictive of blunted cortisol reactivity to a performance-based stressor task (Trier Social Stress Test; TSST) in college students. However, the relationship between cortisol reactivity and psychopathy has not been explored in high risk samples such as incarcerated populations. Further, the role of imprisonment in relation to cortisol stress reactivity has not been previously explored, but could have practical and conceptual consequences in regard to rehabilitation and biological sensitivity to context, respectively. The current study tested the hypotheses that both psychopathic personality traits and amount of time incarcerated are related to cortisol blunting in response to stress among incarcerated young adults. A sample of 49 young adult male offenders was recruited to complete the TSST. Salivary hormone samples were taken just prior to and 20 min post-stressor, and participants were interviewed with the Psychopathy Checklist-Youth Version. Variables quantifying the amount of time at the present facility prior to the date of testing and number of commitments in juvenile facilities were also collected. Correlational analyses indicated that only number of incarcerations was related to blunted cortisol. Hierarchical Linear Modeling revealed that time incarcerated and number of commitments were related to a blunted cortisol response among responders and declining cortisol reactivity among nonresponders, respectively. Controlling for time incarcerated, psychopathic traits were significantly related to cortisol decline in response to the stressor among nonresponders, but were not related to blunted cortisol among responders. Results of this project highlight the potential biological effects of prolonged and repeated incarcerations, and extend our understanding about the relationship between psychopathic traits and cortisol reactivity in an incarcerated sample.

Adolescents', mothers', and fathers' gendered coping strategies during conflict: Youth and parent influences on conflict resolution and psychopathology.

We observed gendered coping strategies and conflict resolution outcomes used by adolescents and parents during a conflict discussion task to evaluate associations with current and later adolescent psychopathology. We studied 137 middle- to upper-middle-class, predominantly Caucasian families of adolescents (aged 11-16 years, 65 males) who represented a range of psychological functioning, including normative, subclinical, and clinical levels of problems. Adolescent coping strategies played key roles both in the extent to which parent-adolescent dyads resolved conflict and in the trajectory of psychopathology symptom severity over a 2-year period. Gender-prototypic adaptive coping strategies were observed in parents but not youth, (i.e., more problem solving by fathers than mothers and more regulated emotion-focused coping by mothers than fathers). Youth-mother dyads more often achieved full resolution of conflict than youth-father dyads. There were generally not bidirectional effects among youth and parents' coping across the discussion except boys' initial use of angry/hostile coping predicted fathers' angry/hostile coping. The child was more influential than the parent on conflict resolution. This extended to exacerbation/alleviation of psychopathology over 2 years: higher conflict resolution mediated the association of adolescents' use of problem-focused coping with decreases in symptom severity over time. Lower conflict resolution mediated the association of adolescents' use of angry/hostile emotion coping with increases in symptom severity over time. Implications of findings are considered within a broadened context of the nature of coping and conflict resolution in youth-parent interactions, as well as on how these processes impact youth well-being and dysfunction over time.

Experiences in the military may impact dual-axis neuroendocrine processes in veterans.

Military stressors such as survival training can affect endocrine functioning in the short term, and combat has been associated with endocrine changes linked to psychopathology. However, studies with military samples examining whether there are individual differences in these changes as part of normal development, or as an adaptive mechanism in adulthood are lacking. This study examined whether exposure to combat in a sample of veterans was associated with differential endocrine activity to a laboratory frustration task. Results indicated that Army veterans demonstrated significant testosterone reactivity to frustration and negative coupling between cortisol and testosterone. Alternatively, Navy and Marine veterans demonstrated little testosterone reactivity to frustration and positive coupling between cortisol and testosterone. Positive cortisol-testosterone coupling was stronger among individuals who had more dangerous combat experiences. This latter pattern may better prepare individuals for stressful life experiences and supports the contention that adulthood stressors may calibrate endocrine systems. Results are explained in the context of the Adaptive Calibration Model (Ellis et al., 2012, Developmental Psychology, 48(3), 598-623) which proposes that exposure to key environmental dimensions during endocrinologically malleable life stages (e.g., puberty) can change stress responsivity, resulting in a faster life history trajectory (e.g., increased risk-taking and aggression).

Context influences the interplay of endocrine axes across the day.

The current investigation examined stressors upon the coupling of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. Emphasis is placed on the moderating role of context and time. One hundred and eighteen adolescent males and females provided up to 32 diurnal saliva samples across a visit to a research lab. This visit constituted a day-long stress through which the impact on HPA-HPG axis coupling could be assessed. We tested four models of HPA-HPG axis coupling across the lab day. Sex and stress hormones operated synchronously (ß = .404, p < .001), and the coupling of sex and stress hormones was moderated by the stress of the lab day (ß = .010, p = .05). This pattern of co-elevation did not appear to be moderated by the distal experience of early life adversity. Findings suggest that the notion of "stress" must disentangle proximal and distal challenges, each of which appears to impact neurobiological processes.

A dual-axis approach to understanding neuroendocrine development.

This introduction sets out to present a series of paper about a novel perspective regarding stress and sex hormones, or what the authors within this special issue term "coupling" of hypothalamic-pituitary-adrenal and--gonadal axes. This view postulates that these axes do not necessarily operate in opposition, but can operate together as evidenced empirically as a positive within-person association between stress hormones like cortisol or sex hormones like testosterone. A wealth of papers within the special issue demonstrate positive coupling across acute, diurnal, basal, and longitudinal timeframes and across several different types of contexts. Reviews were meant to challenge whether this was physiologically plausible. Consistently, sophisticated statistical models were utilized in order to show a template for how to model positive coupling and to ensure that coupling was a within-person phenomenon. We cautiously considered positive coupling until the consistency of observing coupling was robust enough for us to consider challenging the prevailing oppositional view of these axes. We do so to acknowledge that there are contexts, moments and stages in which the function of these axes should work together: for example when contexts are both stressful and challenging or at developmental stages (like adolescence) in which the youth must grow up despite the storm and stress of youth. We hope that by putting forward a functional dual-axis approach, the field will be able to consider when and how these axes work together.

Within-person coupling of changes in cortisol, testosterone, and DHEA across the day in adolescents.

We comprehensively examined within-person and between-person associations between cortisol and DHEA and cortisol and testosterone across the day. Data are from a sample of 213 adolescents aged 11-16 (M = 13.7, SD = 1.5 years) from the Northeastern US who were oversampled for psychopathology symptoms. Six repeated measures of hormone levels across 3 days were used to test three specific questions of cortisol-DHEA and cortisol-testosterone associations within individuals (coupling) across the day, and one question of cortisol-DHEA and cortisol-testosterone diurnal slopes were associated between adolescents. Results consistently revealed positive cortisol-DHEA and cortisol-testosterone coupling across the day, often more pronounced in girls relative to boys. Cortisol and DHEA slopes were positively associated, whereas cortisol and testosterone were negatively associated between-adolescents. Findings suggest multiple mechanisms and highlight the multifaceted nature of associations of hormone changes during adolescence and importance of considering both axes for between- and within-person aspects of neuroendocrine development.

Neuroendocrine coupling across adolescence and the longitudinal influence of early life stress.

Drawing on conceptual models illustrating the advantages of a multisystemic, interactive, developmental approach to understanding development, the present study examines the covariation of stress and sex hormones across the adolescent transition and the effect of early life stress (ELS) on neuroendocrine coupling to gain insight into atypical development. Morning levels of cortisol, testosterone, and dehydroepiandrosterone (DHEA) were assessed at ages 11, 13, and 15; ELS was assessed during the infancy and preschool periods. Hierarchical linear modeling revealed that cortisol-DHEA coupling patterns progressed to tight, positive coupling across adolescence. Cortisol-testosterone coupling was positive at age 11 but became more negative at ages 13 and 15. Exposure to ELS resulted in more adultlike neuroendocrine coupling patterns earlier in life than non-exposed youth; however the effect of ELS on cortisol-testosterone coupling was unique to girls. Results illustrate trajectories of neuroendocrine coupling that may be unique to adolescence. Moderation by ELS suggests that early stress exposure may prompt earlier adultlike neuroendocrine coupling, particularly within girls, which may contribute to early pubertal development.