When virtual reality becomes psychoneuroendocrine reality: A stress(or) review.

This review article was awarded the Dirk Hellhammer award from ISPNE in 2023. It explores the dynamic relationship between stressors and stress from a historical view as well as a vision towards the future of stress research via virtual reality (VR). We introduce the concept of a "syncytium," a permeable boundary that blurs the distinction between stress and stressor, in order to understand why the field of stress biology continues to inadequately measure stress alone as a proxy for the force of external stressors. Using Virtual Reality (VR) as an illustrative example to explicate the black box of stressors, we examine the distinction between 'immersion' and 'presence' as analogous terms for stressor and stress, respectively. We argue that the conventional psychological approaches to stress measurement and appraisal theory unfortunately fall short in quantifying the force of the stressor, leading to reverse causality fallacies. Further, the concept of affordances is introduced as an ecological or holistic tool to measure and design a stressor's force, bridging the gap between the external environment and an individual's physiological response to stress. Affordances also serve to ameliorate shortcomings in stress appraisal by integrating ecological interdependencies. By combining VR and psychobiological measures, this paper aims to unravel the complexity of the stressor-stress syncytium, highlighting the necessity of assessing both the internal and external facets to gain a holistic understanding of stress physiology and shift away from reverse causality reasoning. We find that the utility of VR extends beyond presence to include affordance-based measures of immersion, which can effectively model stressor force. Future research should prioritize the development of tools that can measure both immersion and presence, thereby providing a more comprehensive understanding of how external stressors interact with individual psychological states.

Cortisol's diurnal rhythm indexes the neurobiological impact of child adversity in adolescence.

Adverse early life experiences, such as child maltreatment, shapes hypothalamic-pituitary-adrenal (HPA) activity. The impact of social context is often probed through laboratory stress reactivity, yet child maltreatment is a severe form of chronic stress that recalibrates even stable or relatively inflexible stress systems such as cortisol's diurnal rhythm. This study was designed to determine how different social contexts, which place divergent demands on children, shape cortisol's diurnal rhythm. Participants include 120 adolescents (9-14 years), including 42 youth with substantiated child physical abuse. Up to 32 saliva samples were obtained in the laboratory, on days youth stayed home, and on school days. A 3-level hierarchical linear model examined cortisol within each day and extracted the diurnal rhythm at level 1; across days at level 2; and between-individual differences in cortisol and its rhythm at level 3. While cortisol's diurnal rhythm was flattened when youth were in the novel laboratory context, the impact of maltreatment was observed within the home context such that maltreated children had persistently flattened diurnal rhythms. The effect of maltreatment overlapped with current chronic interpersonal family stress. Results are consistent with the idea that maltreatment exerts a robust, detrimental impact on the HPA axis and are interpreted in the context of less flexibility and rhythmicity. The HPA axis adapts by encoding signifiers of relevant harsh or unpredictable environments, and the extreme stress of physical abuse in the family setting may be one of these environments which calibrates the developing child's stress responsive system, even throughout a developmental stage in which the family takes on diminishing importance.

Transgenerational effect of Mothers' experiences of discrimination on Black youths' hormone coupling in response to laboratory stress.

Exposure to pervasive racial discrimination of Black Americans is transgenerational in that mothers' experiences of discriminatory violence impacts their children. This study explored whether stress-related biomarkers reflect transgenerational racial stress by implementing a "dual activation" framework to probe how adrenal and gonadal hormones underlying adolescent development are co-regulated during a laboratory stressor. Data were collected from 120 Black families in the United States. Children completed the Trier Social Stress Task (TSST-C) and provided 4 saliva samples across 2 days that were assayed for cortisol (C), dehydroepiandrosterone (DHEA), and testosterone (T). Mothers reported their experiences of total discrimination and racial discrimination related to skin color/race. Thirty four percent reported experiences of discrimination and on average 46.7% reported experiences of discrimination due to their race or skin tone. Mothers' experiences of racial discrimination were associated with their child's hormonal reactivity to and recovery from the TSST-C. Youth showed stronger positive hormone coupling between C-T if their mother experienced greater discrimination. Mothers' experiences of racial discrimination influenced both C-T coupling and youths' cortisol recovery from the TSST-C. For youths with high testosterone, cortisol recovery was blunted. Results suggest that associations between racism and hormonal stress response may be transgenerational. Mothers' experiences of discrimination had a profound impact on their children's hormonal co-regulation.

Associations between multi-method latent factors of puberty and brain structure in adolescent girls.

Pubertal processes are associated with structural brain development, but studies have produced inconsistent findings that may relate to different measurements of puberty. Measuring both hormones and physical characteristics is important for capturing variation in neurobiological development. The current study explored associations between cortical thickness and latent factors from multi-method pubertal data in 174 early adolescent girls aged 10-13 years in the Transitions in Adolescent Girls (TAG) Study. Our multi-method approach used self-reported physical characteristics and hormone levels (dehydroepiandrosterone (DHEA), testosterone (T), and estradiol (E2) from saliva) to estimate an overall pubertal factor and for each process of adrenarche and gonadarche. There were negative associations between the overall puberty factor representing later stage and thickness in the posterior cortex, including the occipital cortices and extending laterally to the parietal lobe. However, the multi-method latent factor had weaker cortical associations when examining the adnearcheal process alone, suggesting physical characteristics and hormones capture different aspects of neurobiological development during adrenarche. Controlling for age weakened some of these associations. These findings show that associations between pubertal stage and cortical thickness differ depending on the measurement method and the pubertal process, and both should be considered in future confirmatory studies on the developing brain.

Fronto-amygdala resting state functional connectivity is associated with anxiety symptoms among adolescent girls more advanced in pubertal maturation.

Early adolescence, with the onset of puberty, is an important period when sex differences in anxiety emerge, with girls reporting significantly higher anxiety symptoms than boys. This study examined the role of puberty on fronto-amygdala functional connectivity and risk of anxiety symptoms in 70 girls (age 11-13) who completed a resting state fMRI scan, self-report measures of anxiety symptoms and pubertal status, and provided basal testosterone levels (64 girls). Resting state fMRI data were preprocessed using fMRIPrep and connectivity indices were extracted from ventromedial prefrontal cortex (vmPFC) and amygdala regions-of-interest. We tested moderated mediation models and hypothesized that vmPFC-amygdala would mediate the relation between three indices of puberty (testosterone and adrenarcheal/gonadarcheal development) and anxiety, with puberty moderating the relation between connectivity and anxiety. Results showed a significant moderation effect of testosterone and adrenarcheal development in the right amygdala and a rostral/dorsal area of the vmPFC and of gonadarcheal development in the left amygdala and a medial area of the vmPFC on anxiety symptoms. Simple slope analyses showed that vmPFC-amygdala connectivity was negatively associated with anxiety only in girls more advanced in puberty suggesting that sensitivity to the effects of puberty on fronto-amygdala function could contribute to risk for anxiety disorders among adolescent girls.

Childhood trauma, earlier pubertal timing, and psychopathology in adolescence: The role of corticolimbic development.

Earlier pubertal development appears to be one pathway through which childhood trauma contributes to psychopathology in adolescence. Puberty-related changes in neural networks involved in emotion processing, namely the amygdala-medial prefrontal (mPFC) circuit, may be a potential mechanism linking trauma and adolescent psychopathology. Our participants were 227 youth between 10 and 13 years of age who completed assessments of threat and deprivation-related experiences of adversity, pubertal stage, and internalizing and externalizing symptoms. A subset (n = 149) also underwent a functional MRI scan while passively viewing fearful and calm faces. Potential mechanisms linking childhood trauma with psychopathology, encompassing earlier pubertal timing and neural response to aversive stimuli were explored. Earlier pubertal development was associated with childhood trauma as well as increased externalizing symptoms in boys only. Earlier pubertal timing in males and females was negatively associated with activation in bilateral amygdala, hippocampal, and fusiform regions when comparing fearful and calm faces. However, amygdala-mPFC connectivity showed no association with pubertal timing or psychopathology symptoms. These findings do not support accelerated amygdala-mPFC development as a mechanism linking childhood trauma and psychopathology, but instead provide support for the role of pubertal development in normative decreases in limbic activation across development.

Aging and Pubertal Development Differentially Predict Symptoms of ADHD, Depression, and Impairment in Children and Adolescents: An Eight-Year Longitudinal Study.

Activational effects of the reproductive neuroendocrine system may explain why some youths with ADHD are at greater risk for exacerbated ADHD symptoms (hyperactivity, inattention, impulsivity) during adolescence. For youths diagnosed with ADHD, first signs of ADHD symptoms become noticeable by multiple reporters (e.g., teachers, parents) when children enter schools, typically around kindergarten. The current study examined possible sex differences in ADHD, impairment, and comorbidity due to pubertal effects, as the role of pubertal development in ADHD is understudied. ADHD symptoms, depressive symptoms, impairment, and pubertal stage were assessed annually by multiple reporters in a well-characterized community sample of 849 children over-recruited for ADHD over eight years. Ages ranged from 7 to 13 years (38.16% female) at wave 1. Multilevel models indicated that males had higher levels of hyperactivity, impulsivity, and inattention than females, but that females had higher levels of impairment than males. Inattention symptoms did not show marked maturation changes. Hyperactivity and impulsivity declined as youth aged and impairment increased as youth aged. Lastly, depressive symptoms largely increased as youth aged and were higher amongst youth at later pubertal stages. Put together, aging and pubertal development are associated with improved ADHD symptoms but not for youth with high impairment. Findings from this study contributes to understanding the role that aging, pubertal status, and pubertal development plays in ADHD, impairment, and comorbidity in children and adolescents.

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.

The Role of Puberty and Sex on Brain Structure in Adolescents With Anxiety Following Concussion.

BACKGROUND: Adolescence represents a window of vulnerability for developing psychological symptoms following concussion, especially in girls. Concussion-related lesions in emotion regulation circuits may help explain these symptoms. However, the contribution of sex and pubertal maturation remains unclear. Using the neurite density index (NDI) in emotion regulation tracts (left/right cingulum bundle [CB], forceps minor [FMIN], and left/right uncinate fasciculus), we sought to elucidate these relationships. METHODS: No adolescent had a history of anxiety and/or depression. The Screen for Child Anxiety Related Emotional Disorders and Children's Depression Rating Scale were used at scan to assess anxiety and depressive symptoms in 55 concussed adolescents (41.8% girls) and 50 control adolescents with no current/history of concussion (44% girls). We evaluated if a mediation-moderation model including the NDI (mediation) and sex or pubertal status (moderation) could help explain this relationship. RESULTS: Relative to control adolescents, concussed adolescents showed higher anxiety (p = .003) and lower NDI, with those at more advanced pubertal maturation showing greater abnormalities in 4 clusters: the left CB frontal (p = .002), right CB frontal (p = .011), FMIN left-sided (p = .003), and FMIN right-sided (p = .003). Across all concussed adolescents, lower NDI in the left CB frontal and FMIN left-sided clusters partially mediated the association between concussion and anxiety, with the CB being specific to female adolescents. These effects did not explain depressive symptoms. CONCLUSIONS: Our findings indicate that lower NDI in the CB and FMIN may help explain anxiety following concussion and that adolescents at more advanced (vs less advanced) status of pubertal maturation may be more vulnerable to concussion-related injuries, especially in girls.

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.

Impact of hair type, hair sample weight, external hair exposures, and race on cumulative hair cortisol.

The biomarker cortisol assesses the impact of biopsychosocial stressors that activate the stress response system. Hair has emerged as a valid and non-invasive means of gauging cumulative cortisol deposited over month-long periods of time. Established protocols for the extraction of hair cortisol are being validated and refined in humans, yet methodological information about hair characteristics on cortisol remains limited. In addition to external hair exposures (e.g. dye, time spent outside), we examined hair categorization or type (e.g. kinky, straight) by extending a hair typing methodology for scientific use that is currently popular among hair care professionals. We then examined the interaction between hair type and race on cortisol levels with a hair questionnaire. Three studies were pooled to investigate how sample weight, hair type, race, heat exposures, and hair treatments impacted cumulative hair cortisol concentrations. Study 1 consisted of Adult Kenyan Medical Workers (N = 44); Study 2 Mexican and Mexican Americans (N = 106); and Study 3 American Youth (N = 107). We found significantly higher cortisol in 5 mg of hair when compared to larger sample weights, and higher cortisol in those who spent more time outdoors. Cortisol concentrations differed between racial groups and varied by hair type; moreover, there were directional differences in cumulative cortisol from straighter to curlier hair types which depended on racial group. In addition to demonstrating the impact of relatively novel control factors like hair sample weight, outdoor exposure, and hair type, the present study illustrates the importance of disentangling hair type and race to understand variability in cumulative hair cortisol. These influences should be included in future studies that measure hair cortisol.

Evoking stress reactivity in virtual reality: A systematic review and meta-analysis.

BACKGROUND: Virtual reality (VR) research probes stress environments that are infeasible to create in the real world. However, because research simulations are applied to narrow populations, it remains unclear if VR simulations can stimulate a broadly applicable stress-response. This systematic review and meta-analysis was conducted on studies using VR stress tasks and biomarkers. METHODS: Included papers (N = 52) measured cortisol, heart rate (HR), galvanic skin response (GSR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory sinus arrhythmia (RSA), parasympathetic activity (RMSSD), sympathovagal balance (LF/HF), and/or salivary alpha-amylase (sAA). Effect sizes (ES) and confidence intervals (CI) were calculated based on standardized mean change of baseline-to-peak biomarker levels. RESULTS: From baseline-to-peak (ES, CI), analyses showed a statistically significant change in cortisol (0.56, 0.28-0.83), HR (0.68, 0.53-0.82), GSR (0.59, 0.36-0.82), SBP (.55, 0.19-0.90), DBP (.64, 0.23-1.05), RSA (-0.59, -0.88 to -0.30), and sAA (0.27, 0.092-0.45). There was no effect for RMSSD and LF/HF. CONCLUSION: VR stress tasks elicited a varied magnitude of physiological stress reactivity. VR may be an effective tool in stress research.

Prenatal programming of developmental trajectories for obesity risk and early pubertal timing.

The thrifty phenotype and fetal overnutrition hypotheses are two developmental hypotheses that originated from the developmental origins of health and disease (DOHaD) perspective. The DOHaD posits that exposures experienced prenatally and early in life may influence health outcomes through altering form and function of internal organs related to metabolic processes. Obesity risk and early pubertal timing might be influenced by similar mechanisms. The thrifty phenotype hypothesis is primarily characterized by experiencing a deprivation of nutrients during gestation paired with an energy rich postnatal environment. The fetal overnutrition hypothesis says that obesity experienced prenatally will be associated with increased lifetime risk of obesity in the offspring. Both hypotheses were tested by examining developmental pathways from genetic and prenatal risk through early growth trajectories (birth to 7 years) to pubertal timing at age 11 years. Participants included 361 children adopted at birth (57% male; 57% non-Hispanic White, 11% Black, 9% Hispanic; adoptive family income Mdn = $70,000-$100,000, birth family income Mdn = < $15,000). Associations between boys' childhood body mass index (BMI) and pubertal timing were confounded by genetics, prenatal risk, and early growth. The thrifty phenotype hypothesis was partially supported for boys' childhood BMI (at ages 4 to 7 years). Both hypotheses were partially supported for girls' childhood BMI but not pubertal timing. A novel Gene × Prenatal Risk interaction showed that genetic risk predicted girls' childhood BMI most strongly at adequate compared with at excessive levels of gestational weight gain. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Naturalistic Study Assessing the Impact of Daytime Running Lights and Vehicle Passing events on Cyclist's Physiological Stress.

Bicyclists are vulnerable road users who are at a greater risk for injury and fatality during crashes. Additionally, the "near-miss" incidents they experience during regular trips can increase the perceived risk and deter them from riding again. This paper aims to use naturalistic bicycling data collected in Johnson County, Iowa to: 1) study the effect of factors such as road surface type, parked vehicles, pavement markings and car passing events on cyclists' physiological stress and 2) understand the effect of daytime running lights (DRL) as an on-bicycle safety system in providing comfort to cyclists and highlight of their presence on the road to other vehicles. A total of 37 participants were recruited to complete trips over two weekends, one weekend with DRL and the other without DRL. Recruitment was specifically targeted toward cyclists who expressed discomfort riding in traffic. Data were collected using a front forward facing camera, GPS, and a vehicle lateral passing distance sensor mounted on the bicycle and a Empatica E4 wrist band (providing physiological data such as electrodermal activity; EDA) worn by the cyclist. Data from those sources were cleaned, processed, merged, and aggregated into time windows depicting car passing and no car passing events. Mixed effects models were used to study the cyclists' skin conductance response (phasic EDA) and baseline skin conductance level (tonic EDA). Car passing, parked vehicles, and roads with dashed centerline markings were observed to increase the cyclists stress. The use of DRL had negligible impact on cyclist stress on roads.

Multimethod assessment of pubertal timing and associations with internalizing psychopathology in early adolescent girls.

Early pubertal timing has consistently been associated with internalizing psychopathology in adolescent girls. Here, we aimed to examine whether the association between timing and mental health outcomes varies by measurement of pubertal timing and internalizing psychopathology, differs between adrenarcheal and gonadarcheal processes, and is stronger concurrently or prospectively. We assessed 174 female adolescents (age 10.0-13.0 at Time 1) twice, with an 18-month interval. Participants provided self-reported assessments of depression/anxiety symptoms and pubertal development, subjective pubertal timing, and date of menarche. Their parents/guardians also reported on the adolescent's pubertal development and subjective pubertal timing. We assessed salivary dehydroepiandrosterone (DHEA), testosterone, and estradiol levels and conducted clinical interviews to determine the presence of case level internalizing disorders. From these data, we computed 11 measures of pubertal timing at both time points, as well as seven measures of internalizing psychopathology, and entered these in a Specification Curve Analysis. Overall, earlier pubertal timing was associated with increased internalizing psychopathology. Associations were stronger prospectively than concurrently, suggesting that timing of early pubertal processes might be especially important for later risk of mental illness. Associations were strongest when pubertal timing was based on the Tanner Stage Line Drawings and when the outcome was case-level Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) depression or Hierarchical Taxonomy of Psychopathology (HiTOP) distress disorders. Timing based on hormone levels was not associated with internalizing psychopathology, suggesting that psychosocial mechanisms, captured by timing measures of visible physical characteristics might be more meaningful determinants of internalizing psychopathology than biological ones in adolescent girls. Future research should precisely examine these psychosocial mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Effects of Group Therapeutic Singing on Cortisol and Motor Symptoms in Persons With Parkinson's Disease.

The inclusion of music into the treatment plan for persons with Parkinson's disease (PD) may be a viable strategy to target multiple motor symptoms. However, potential mechanisms to explain why music has an impact on multiple motor symptoms in persons with PD remain understudied. The purpose of this study was to examine the acute effects of 1 h of group therapeutic singing (GTS) on physiological measures of stress and clinical motor symptoms in persons with PD. We posit that improvement in motor symptoms after GTS may be related to stress reduction. Seventeen participants with PD completed 1 h of GTS and eight participants completed 1 h of a quiet reading (control session). Cortisol was collected via passive drool immediately before and after the singing and control session. The Unified Parkinson's Disease Rating Scale (UPDRS) Part-III (motor examination) was also video-recorded immediately before and after the singing and control session and scored by two raters masked to time and condition. Secondary outcome measures for quality of life, depression, and mood were collected. Results revealed no significant change in cortisol or motor UPDRS scores, as well as no significant relationship between cortisol and motor UPDRS scores. There was a trend for the singing group to report feeling less sad compared to the control group after the 1-h session (effect size = 0.86), and heart rate increased in the singing group while heart rate decreased in the control group after the 1-h session. These results suggest that an acute session of GTS is not unduly stressful and promotes the use of GTS for persons with PD. Multiple mechanisms may underlie the benefits of GTS for persons with PD. Further exploring potential mechanisms by which singing improves motor symptoms in persons with PD will provide greater insight on the therapeutic use of music for persons with PD.