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Terrorism and trauma survivors often experience changes in biomarkers of autonomic, inflammatory and hypothalamic-pituitary-adrenal (HPA) axis assessed at various times. Research suggests interactions of these systems in chronic stress.
Study Objective:
This unprecedented retrospective study explores long-term stress biomarkers in three systems in terrorism survivors.
Methods:
Sixty healthy, direct terrorism survivors were compared to non-exposed community members for cardiovascular reactivity to a trauma script, morning salivary cortisol, interleukin 1-β (IL-1β), and interleukin 2-R (IL-2R). Survivors’ biomarkers were correlated with psychiatric symptoms and diagnoses and reported functioning and well-being seven years after the Oklahoma City (OKC) bombing.
Main outcome measures were the Diagnostic Interview Schedule (DIS) Disaster Supplement for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnoses, Impact of Events Scale-Revised (IES-R), Beck Depression Inventory-II (BDI-II), Distress and Functioning Scale (DAF), and General Physical Well-Being Scale.
Results:
Survivors had higher inflammatory IL-1β, lower anti-inflammatory IL-2R, lower cortisol, higher resting diastolic blood pressure (BP), and less cardiovascular reactivity to a trauma script than comparisons. Survivors’ mean posttraumatic stress (PTS) symptom levels did not differ from comparisons, but survivors reported worse well-being. None of survivors’ biomarkers correlated with PTS or depressive symptoms or diagnoses or reported functioning.
Conclusions:
Alterations of biological stress measures in cardiovascular, inflammatory, and cortisol systems coexisted as an apparent generalized long-term response to terrorism rather than related to specific gauges of mental health. Potential interactions of biomarkers long after trauma exposure is discussed considering relevant research. Longer-term follow-up could determine whether biomarkers continue to differ or correlate with subjective measures, or if they accompany health problems over time. Given recent international terrorism, understanding long-term sequelae among direct survivors is increasingly relevant.
This study investigated the psychometric properties of the Highly Sensitive Child-Rating System (HSC-RS), the existence of sensitivity groups, and the characterization of sensitivity at behavioral, genetic, and physiological levels in 541 preschoolers (M(SD)age = 3.56(0.27); 45%male; 87%Caucasian). Temperament, genetic, cortisol, and electroencephalography asymmetry data were collected in subsamples (n = 94-476). Results showed a reliable observational measure of sensitivity. Confirmatory factor and latent class analysis supported a one-factor solution and three sensitivity groups, that are a low (23.3%), medium (54.2%), and a high (22.5%) sensitivity group. Hierarchical regression analyses showed moderate associations between HSC-RS and observed temperament traits (i.e., behavioral level). In addition, a small negative association between HSC-RS and a genome-wide association study polygenic risk score (GWAS PGS) for Attention Deficit Hyperactivity Disorder was found. No relations with candidate genes, other GWAS PGS phenotypes, and physiological measures were found. Implications of our findings and possible explanations for a lack of these associations are discussed.
Using [18F]altanserin, a serotonin 2A receptor (5-HT2AR) antagonist Positron Emission Tomography (PET) tracer, a positive association between cortical 5-HT2AR binding and the inward-directed facets of neuroticism has been demonstrated in healthy individuals. Psilocybin, a 5-HT2AR agonist, shows promise for the treatment of depression, reducing neuroticism and mood symptoms potentially via hypothalamic-pituitary-adrenal (HPA) modulation. 5-HT2AR and neuroticism are both modulated by HPA axis function.
Aims
In this study, we examined whether the association between 5-HT2AR binding and the inward facets of neuroticism can be replicated in an independent healthy cohort using the new 5-HT2AR agonist tracer [11C]Cimbi-36, and if their association is moderated by cortisol awakening response (CAR), an index of HPA axis function. If so, this could advance mechanistic insights into interventions that target the 5-HT2AR and reduce neuroticism.
Method
Eighty healthy volunteers underwent [11C]Cimbi-36 PET scans and completed the NEO personality inventory (NEO-PI-R) for the assessment of neuroticism. Salivary samples were available for determination of CAR in 70 of the participants. Using linear latent variable models, we evaluated the association between 5-HT2AR binding and inward facets of neuroticism, namely depression, anxiety, self-consciousness and vulnerability to stress, and whether CAR moderated this association.
Results
The study confirms the positive association between 5-HT2AR binding and the inward facets of neuroticism (β = 0.01, 95% CI = [0.0005: 0.02], P = 0.04), and this association is independent of CAR (P = 0.33).
Conclusions
The findings prompt consideration of whether novel interventions such as psilocybin that actively targets 5-HT2AR and causes changes in personality could be particularly beneficial if implemented as a targeted approach based on neuroticism profiles.
Despite the added value of multisystem (relative to traditional single-system) approaches for characterizing biological processes linked to risk for psychopathology (e.g., neuroendocrine stress responsivity; Buss et al., 2019; Quas et al., 2014), no study to date has evaluated whether multisystem processes may serve as viable biological targets of intervention. Utilizing a multiple-levels-of-analysis approach (Cicchetti & Dawson, 2002), this person-centered study examined whether stress-adapted patterns of hypothalamus–pituitary–adrenal (HPA) axis and sympathetic-adrenomedullary (SAM) system co-activation were amenable to change following the Building a Strong Identity and Coping Skills intervention (BaSICS; Wadsworth et al., 2022). Preadolescents exposed to concentrated poverty (n = 112, Mage = 11.78 years, 57.1% female, 54% assigned to intervention; 40% Hispanic, 63% Black, 20% White) completed questionnaires and the Trier Social Stress Test at both pre- and posttest. Multitrajectory modeling of cortisol and alpha-amylase levels identified four pretest and posttest HPA-SAM co-activation profiles. At pretest, youth exhibiting Asymmetric Nos. 1 & 2 HPA-SAM co-activation reported greater maladjustment relative to youth with Symmetric Nos. 1 & 2 co-activation. Youth exhibiting Asymmetric No. 1 co-activation at pretest were more likely to exhibit Symmetric No. 1 co-activation following BaSICS relative to control. Findings highlight the potential of BaSICS to restore neuroendocrine stress response function in impoverished youth, pointing to HPA–SAM co-activation as a potential biological target of preventive intervention in this population.
The endorsement of conspiracy theories may be increased by subjectively perceived stress. Yet, it is not known whether this correlation is caused by the effects of the acute stress reaction on the brain or other psychological, social, or methodological factors. The effect of an experimentally induced acute stress reaction on conspiracy thinking was tested on a sample (n = 115) of students of medicine. Although the stress procedure caused a substantial increase in salivary cortisol, there was no significant effect on endorsing conspiracy theories or adopting conspiracy interpretations of novel information. The results confirmed no effect of the acute stress reaction on conspiracy thinking, suggesting it may be absent or weaker than expected. The study demonstrated the viability of psychophysiological experimental design in conspiracy research and may inspire further examination of the physiological mechanisms underlying susceptibility to conspiracy theories.
Depressive disorders in adolescents affect all aspects of life and impose a very large burden of disease. Sleep is frequently affected by depression and is crucial for facing challenges during development. One of the postulated reasons for depression-induced sleep disruption is dysregulation of the physiological stress system.
Aims
To investigate the links of adolescent depressive disorders with subjective sleep quality, objective sleep quality, and the course of cortisol and alpha-amylase after awakening.
Method
We compared subjective sleep quality (via daily questionnaires) and objective sleep quality (via actigraphy measurement) of 35 adolescents with depressive disorders and 29 healthy controls over 7 consecutive days. In addition, saliva samples were collected on 3 days to examine cortisol and alpha-amylase patterns after awakening.
Results
No significant differences in cortisol or alpha-amylase awakening responses were observed between participants with depressive disorders and healthy controls. We found severe reductions in subjective sleep quality in the depression group (Z = −5.19, P < 0.001, d = 1.80) and a prolonged actigraphy-measured sleep onset latency (Z = −2.42, P = 0.015, d = 0.64) compared with controls. Reductions in subjective sleep quality were partially correlated with objective sleep measures (sleep onset latency: r = −0.270, P = 0.004, sleep efficiency: r = 0.215, P = 0.017).
Conclusions
Sleep onset latency seems to aggravate depressive symptoms and to have an important role in perception of sleep quality. Adolescents with depressive disorders should be supported regarding the establishment of good sleep hygiene and avoiding activities that may impede falling asleep.
High-risk pregnancies elevate maternal stress, impacting offspring neurodevelopment and behavior. This study, involving 112 participants, aimed to compare perceived stress, neurodevelopment, and behavior in high-risk and low-risk pregnancies. Two groups, high-risk and low-risk, were assessed during pregnancy for stress using hair cortisol and psychological analysis. At 24 months post-birth, their children’s neurodevelopment and behavior were evaluated. Results revealed higher perceived stress and pregnancy-related concerns in high-risk pregnancies, contrasting with low-risk pregnancies. Offspring from high-risk pregnancies displayed elevated internalizing behavior scores, while low-risk pregnancies showed higher externalizing behavior scores. Additionally, women in low-risk pregnancies exhibited increased cortisol concentrations 24 months post-delivery. These findings underscore the necessity for early stress detection and prevention programs during pregnancy, particularly in high-risk cases, to enhance maternal and infant health.
Dante Cicchetti’s remarkable contributions to the field of developmental psychopathology include the advancement of key principles such as the interplay of typical and atypical development, multifinality and equifinality, the dynamic processes of resilience, and the integration of multiple levels of analysis into developmental theories. In this paper we assert that person-centered data analytic methods are particularly well-suited to advancing these tenets of developmental psychopathology. We illustrate their utility with a brief novel empirical study focused on underlying patterns of childhood neuroendocrine regulation and prospective links with emerging adult functioning. Results indicate that a childhood neuroendocrine profile marked by high diurnal cortisol paired with low diurnal DHEA was uniquely associated with more adaptive functioning in emerging adulthood. We discuss these findings, and person-centered methods more broadly, within the future of developmental psychopathology.
Adrenal insufficiency can be either primary, resulting from destruction of the adrenal gland, or secondary, resulting from a deficiency of ACTH (adrenocorticotropic hormone, corticotropin).
Adrenal crisis is either the acute development of severe adrenal insufficiency or a rapid deterioration from baseline chronic adrenal insufficiency (which is often insidious) brought on by a stressor.
The adrenal gland (made up of cortex and medulla) produces three categories of steroids: glucocorticoids (cortisol), mineralocorticoids (aldosterone) and gonadocorticoids (sex hormones). Aldosterone levels change in response to volume status and sodium intake. Aldosterone maintains sodium and potassium concentration and regulates water balance.
Suicide is a complex public health problem driven by a multitude of biopsychosocial factors and is the result of gene–environment interactions. Psychosocial variables like chronic stress and trauma have biologic ramifications and can contribute to various forms of pathophysiology, dysregulation, and degradation, represented by allostatic load (AL). AL is the wear and tear that stress exerts on the body, and it has been associated with mental health problems and suicide. Fortunately, there are pharmacological and non-pharmacological interventions that may be effective at reducing AL and reversing its effects. Incorporating AL into efforts to promote early risk identification, prevention, and treatment of suicide is an important consideration. Critical next steps are identifying which AL biomarkers are most malleable, which effective treatments reduce AL, and if these reductions of AL are associated with decreased suicide.
Preliminary evidence shows that discordance in stress experience, expression, and physiology (EEP) in adolescents is linked to depression, suicidal ideation (SI), non-suicidal self-injury (NSSI), and brain functioning. This study employs person-centered analysis to probe the relationship between stress responses, psychopathology, and neural patterns in female adolescents who are oversampled for engagement in NSSI.
Methods
Adolescent females (N = 109, ages 12–17) underwent a social stress test from which self-report measures of stress experience, observer ratings of stress expression, and physiological metrics of stress (via salivary cortisol) were obtained. Multi-trajectory modeling was employed to identify concordant and discordant stress EEP groups. Depressive symptoms, SI and attempt, NSSI engagement, frontal and limbic activation to emotional stimuli, and resting state fronto-limbic connectivity were examined in the EEP groups derived from the multi-trajectory models.
Results
Four groups were identified, three of which demonstrated relatively concordant EEP and one which demonstrated discordant EEP (High Experience-High Expression-Low Physiology). Further, replicating past research, the High Experience-High Expression-Low Physiology discordant group exhibited higher depressive symptoms, SI, suicide attempt, and NSSI episodes (only for sensitivity analyses based on past year) relative to other EEP groups. No significant group differences in brain functioning emerged.
Conclusion
Results indicate that within-person, multi-level patterns in stress responding capture risk for dysfunction including depression and self-injurious thoughts and behaviors. Further interrogating of system-level stress functioning may better inform assessment and intervention efforts.
Increasing age and puberty affect the hypothalamic pituitary adrenal (HPA) axis maturation, which is likely associated with an increase in environmental demands (e.g., social) and vulnerability for the onset of psychiatric conditions (e.g., depression). There is limited research as to whether such patterns are consonant in youth with autism spectrum disorder (ASD), a condition marked by social challenges, dysregulation of the HPA axis, and higher rates of depression setting the stage for enhanced vulnerability during this developmental period.
The current study interrogated diurnal cortisol by examining (1) cortisol expression longitudinally over the pubertal transition between autistic and neurotypical youth, (2) the trajectory of diurnal cortisol and the unique contributions of age vs. puberty, and (3) potential sex differences. As hypothesized, results indicate autistic compared to typically developing youth demonstrate a shallower diurnal slope and elevated evening cortisol. These differences were in the context of higher cortisol and flatter rhythms based on age and pubertal development. Also, sex-based differences emerged such that females in both groups had higher cortisol, flatter slopes, and higher evening cortisol than males. The results show that despite the trait-like stability of diurnal cortisol, HPA maturation is impacted by age, puberty, sex, as well as an ASD diagnosis.
A blunted hypothalamic–pituitary–adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated.
Methods
Seventy-seven participants (17–22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17–22 years old, 24 women).
Results
Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response.
Conclusions
This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.
Childhood adversity has been associated with hypothalamic–pituitary–adrenal axis dysregulation, which is associated with mental and physical health consequences. However, associations between childhood adversity and cortisol regulation in the current literature vary in magnitude and direction. This multilevel meta-analysis examines the association between childhood adversity and diurnal cortisol measures, as well as potential moderators of these effects (adversity timing and type, study or sample characteristics). A search was conducted in online databases PsycINFO and PubMed for papers written in English. After screening for exclusion criteria (papers examining animals, pregnant women, people receiving hormonal treatment, people with endocrine disorders, cortisol before age 2 months, or cortisol after an intervention), 303 papers were identified for inclusion. In total, 441 effect sizes were extracted from 156 manuscripts representing 104 studies. A significant overall effect was found between childhood adversity and bedtime cortisol, r = 0.047, 95% CI [0.005, 0.089], t = 2.231, p = 0.028. All other overall and moderation effects were not significant. The lack of overall effects may reflect the importance of the timing and nature of childhood adversity to adversity’s impact on cortisol regulation. Thus, we offer concrete recommendations for testing theoretical models linking early adversity and stress physiology.
Intimate partner violence (IPV) alters women's neurobiological stress response systems. We propose that individual differences early in the attentional processing of threats are associated with these neurobiological mechanisms and contribute to mental illness in this population.
Methods
We assessed attentional bias in relation to threat (AB) in women survivors of IPV (n = 69) and controls (n = 36), and examined overall cortisol secretion using hair cortisol (HC), and stress responsiveness measuring salivary cortisol and α-amylase (sAA) before (T0), and after (T1, T2) an acute psychosocial stress task (Trier Social Stress Test). We used repeated-measures ANCOVAs to explore the associations between Group (IPV, control) and AB with acute stress response, and regression models to examine the associations with mental health symptoms.
Results
There were no between-group differences in HC levels. An interaction between Group and AB was found regarding cortisol reactivity (p < 0.05). IPV women with threat avoidance AB showed a blunted cortisol response compared to controls and to IPV participants with threat vigilance AB. The association between sAA reactivity and the interaction between Group, AB, and time approached significance (p = 0.07), with a trend to lower sAA levels particularly in IPV women with threat avoidance AB. Group and cortisol reactivity were associated with symptoms of depression, generalized anxiety, and post-traumatic stress disorder (8–20% explained variance).
Conclusions
Threat avoidance AB is associated with blunted acute cortisol response among women exposed to chronic stress (IPV). Experiencing IPV and acute cortisol response appear to be clearly implicated in long-term mental health problems.
Longitudinal trajectories of psychopathology in previously institutionalized (PI) youth were identified and biobehavioral emotion regulation processes were examined as developmental mechanisms that predict these trajectories. Mental health data were collected from PI (N = 132) and nonadopted (NA; N = 175) youth across four time points (participant age ranged from 7- to 21-year-old). Using semiparametric group-based methods, the probability that each individual belonged to a distinct group that followed a specific pattern of behavior across time was estimated. We then tested whether unique aspects of emotion regulation (global, observed, and biological) were differentially associated with membership in externalizing and internalizing trajectory groups using multinomial logistic regression models. Four externalizing trajectories were identified for the PI and NA groups. For PI youth, global, observed, and biological emotion regulation processes were uniquely predictive of more adaptive externalizing trajectories. For NA youth, only parent-reported global emotion regulation was predictive of externalizing patterns. Three internalizing trajectories were identified for PI and NA youth. Generally, only parent-reported global emotion regulation predicted internalizing group membership for both PI and NA youth. Results suggest that biobehavioral emotion regulation processes may be particularly important predictors and potential points of intervention when targeting trajectories of externalizing behaviors in PI children.
The stress-vulnerability model has been repeatedly highlighted in relation to the risk, onset and course of psychosis, and has been independently studied in clinical high-risk (CHR) and first-episode psychosis (FEP) populations. Notable in this literature, however, is that there are few studies directly comparing markers of stress response across progressive stages of illness. Here we examined the psychobiological response to the Trier Social Stress Test in 28 CHR (mean age 19.1) and 61 FEP (age 23.0) patients, in order to understand the stage(s) or trajectories in which differences in subjective stress or physiological response occur. The overall clinical sample had greater perceived stress and blunted cortisol (FEP + CHR, n = 89, age 21.7) compared with healthy controls (n = 45, age 22.9). Additional analyses demonstrated elevated heart rate and systolic blood pressure in FEP compared with CHR, but there were no further differences in physiological parameters (cortisol, heart rate, or blood pressure) between stage- or trajectory-based groups. Together, this suggests that individual stress response markers may differentially emerge at particular stages en route to psychosis – and demonstrates how stage-based analyses can shed light on the emergence and evolution of neurobiological changes in mental illness.
Enhanced post-awakening cortisol may serve as a biological marker for individuals with major depressive disorder. However, studies comparing post-awakening cortisol between patients with major depressive disorder (MDD) and healthy controls have produced conflicting findings. The aim of this study was to investigate whether this inconsistency could be due to the effects of childhood trauma.
Methods
A total of N = 112 patients with MDD and healthy controls were divided into four groups according to the presence of childhood trauma. Saliva samples were collected at awakening and 15, 30, 45, and 60 min later. The total cortisol output and the cortisol awakening response (CAR) were calculated.
Results
The total post-awakening cortisol output was significantly higher in patients with MDD as compared to healthy controls, but only in those individuals reporting childhood trauma. The four groups did not differ regarding the CAR.
Conclusions
Elevated post-awakening cortisol in MDD may be confined to those with a history of early life stress. Tailoring and/or augmenting of currently available treatments may be required to meet the specific needs of this population.
The transition to college is a time of increased opportunity and stress spanning multiple domains. Adolescents who encounter significant stress during this transition may be vulnerable to adverse outcomes due to a “wear and tear” of the hypothalamic pituitary adrenal (HPA) axis. Latino/a students may be particularly at-risk for heightened stress exposure due to experiences of both minority-specific and general life stress. Despite this, little is known regarding the cumulative impact of multiple stressors on Latino/a students’ HPA axis functioning. The present study employed a “multi-risk model” approach to examine additive, common, and cumulative effects of multiple stress forms (general, academic, social, financial, bicultural, ethnic/racial discrimination) on diurnal cortisol in a sample of first-year Latino/a college students (N = 196; 64.4% female; Mage = 18.95). Results indicated that no stress forms were additively associated with the cortisol awakening response (CAR), but general stress was associated with a flatter diurnal cortisol slope (DCS) and bicultural stress was linked with a steeper DCS. A college stress latent factor was associated with a lower CAR, whereas a latent factor of discrimination was not associated with diurnal cortisol. Cumulative risk was linked with a lower CAR. Findings highlight the physiological correlates of various stressors experienced by Latino/a college students.
Aggressive reactions to peer victimization may be tempered by hormone levels. Grounded on the dualhormone hypothesis (DHH), which proposes that testosterone (T) is associated with aggressive behavior only when cortisol (C) is low, this study assessed whether the combination of T and C moderated adolescents’ aggressive responses to peer victimization. The study involved 577 adolescents (50.4% girls, aged 12–17 years), who completed measures of online and offline victimization and perpetration of aggressive behavior in three waves over the course of one year. Moreover, they provided salivary samples to measure T and C levels. Multilevel analyses showed a three-way interaction between T, C, and victimization levels for both online and offline aggressive behaviors. In both cases, the adolescents with high T and high C or low T and low C responded with more aggressive behaviors when victimized or provoked by peers. The T/C ratio was only associated with aggressive behavior in the girls’ sample. The results are opposite to those predicted by the DHH, but they are consistent with the findings of other studies that examined aggressive behaviors as reactions to provocations. These results suggest that some combinations of T and C predict higher aggressive reactions to peer victimization.