Aug 2026· Neurobiology of Stress· Vol 44· 0 citations· 76 references
Medicine
Abstract
Background Adolescence is a critical window for autonomic and limbic development and a period of elevated risk for depression. Although autonomic and limbic system function have, independently, been linked to depression, they are coupled and both influenced by early life stress (ELS). We do not yet know, however, whether the association of autonomic activity and limbic connectivity with depressive symptoms differs across dimensions of ELS. Methods Participants were 93 youth (Mage = 12.3) who completed the Trier Social Stress Test (TSST) with continuous electrocardiogram (ECG) recording. ECG-derived high-frequency heart rate variability (RespHRV) was assessed across the baseline, reactivity, and recovery phases of the TSST. Hippocampal-amygdala connectivity was estimated from resting-state data acquired just before the TSST using the Tian atlas. We tested whether RespHRV recovery and connectivity were jointly associated with depressive symptoms and whether ELS dimensions of threat, unpredictability, and deprivation moderated this association. Results Greater RespHRV during recovery was associated with more negative right hippocampal tail-left lateral amygdala connectivity (β = −0.42, q = 0.002). In a joint model, threat (β = −0.34, p = .007) and deprivation (β = −0.36, p = .009 independently moderated this association. Specifically, more negative connectivity predicted fewer symptoms when paired with weaker RespHRV recovery in high-ELS youth, but with stronger RespHRV recovery in low-ELS youth. Conclusions Whether autonomic-limbic coupling buffers or confers risk for depression depends on the early environment in which it developed.
Background Childhood adversity is linked to psychopathology risk and dysregulated stress reactivity; however, unified underlying neural mechanisms are unclear. A central visceral network, including the bed nucleus of the stria terminalis (BNST), amygdala and subgenual anterior cingulate cortex (sgACC), is implicated in affective processes and proximally controls stress reactivity. We examined relationships among childhood adversity, stressor-evoked neural activity/connectivity and affective and cardiovascular outcomes. Methods Participants were adults (n=97, mean age=27.32, SD=4.02, 57 females) uniformly distributed across physical abuse severity. Childhood adversity was assessed by threat (abuse or traumatic events) and socioeconomic deprivation (SED). Participants performed an fMRI stress task with cardiovascular recordings. Linear/curvilinear regressions were performed with threat and deprivation together as predictors of stressor-evoked activity/connectivity. Neural variables showing significant adversity associations were examined as predictors of affective symptoms/diagnoses or cardiovascular responses. Results Threat and SED displayed opposing curvilinear relationships with stressor-evoked amygdala and sgACC activity, respectively: at low and high adversity, amygdala reactivity was greater, whereas sgACC reactivity was blunted. Greater SED was associated with weaker BNST-sgACC connectivity. Blunted amygdala reactivity and lower sgACC reactivity were associated with greater post-traumatic stress symptoms. Affective diagnoses peaked at near-zero BNST-sgACC connectivity. Greater amygdala reactivity was associated with blunted diastolic blood pressure reactivity and recovery. Conclusions The curvilinear relationships suggest adversity-related vulnerability thresholds. Blunted amygdala, lower sgACC reactivity and weaker BNST-sgACC connectivity may confer affective risk, whereas heightened amygdala reactivity may confer cardiovascular risk. Our findings support a central visceral network pathway by which childhood adversity may contribute to affective and cardiovascular health.
N. Kasibhatla, C. W. Peng, H. Karim et al.· medRxiv· 0 citations
BACKGROUND
Depression is a common psychiatric condition posing serious threats to individual physical and mental health. While previous studies have demonstrated that trait emotional regulation (TER) is a protective factor for depression, the neural correlates between TER and depression remain unclear, especially in adolescents. This study aimed to investigate the neurofunctional substrates of TER and its neural link to depressive symptoms in adolescents.
METHODS
Resting-state functional magnetic resonance imaging and a battery of behavioral assessments were administered to 231 general high school students. Whole-brain correlation analyses and prediction analyses were conducted to identify brain regions whose fractional amplitude of low-frequency fluctuations (fALFFs) were associated with TER. We examined the correlation between the identified brain regions and depressive symptoms, and conducted mediation analyses to explore the role of TER in mediating the brain-depression relationship.
RESULTS
TER was significantly correlated negatively with fALFF in the ventromedial prefrontal cortex (VMPFC), and positively with fALFF in the cuneus. Depressive symptoms were negatively correlated with TER, and positively with fALFF in the VMPFC. In mediation analysis, TER had a significant indirect effect on the relationship between the VMPFC activity and depressive symptoms.
CONCLUSIONS
These results reveal the brain functional basis of TER at rest, and identify a neuropsychological pathway through which TER may help ameliorate depression. Our study may provide novel neurobiological insights for early interventions targeting adolescent depression.
Xun Zhang, Min He, Yiling Guo et al.· Journal of Affective Disorde...· 0 citations
OBJECTIVE
Adverse childhood experiences (ACEs) confer risk for depressive symptoms in adulthood, potentially through maladaptive cognitive-affective responses to stress. The neurovisceral integration model suggests that resting respiratory sinus arrhythmia (RSA), an index of parasympathetic regulation, shapes capacity to regulate cognitive-affective stress responses. The present study tested whether stress-related appraisals and perseverative thinking mediated the association between ACEs and depressive symptoms, whether RSA moderated these pathways, and whether effects varied under chronic caregiving stress.
METHODS
Participants were 222 middle-aged mothers (mean age=46.83, SD=6.03) experiencing higher (n=125) and lower (n=97) caregiving stress. ACEs and depressive symptoms were assessed with the Childhood Trauma Questionnaire and CES-D. Perceived threat, perceived control, and perseverative thinking were measured via daily diaries. Resting RSA, CES-D, and daily measures were collected at three timepoints across 30 months.
RESULTS
Lower RSA strengthened the association between ACEs and depressive symptoms (b=0.269, SE=0.060, P<.001). Lower perceived control (b=0.022, 95% CI [0.001, 0.049]) and greater perseverative thinking (b=0.072, 95% CI [0.020, 0.128]) mediated the association between ACEs and depressive symptoms; lower RSA strengthened associations between ACEs and these mediators. Higher ACEs were associated with greater perceived threat among mothers with higher caregiving stress and lower RSA (b=0.014, SE=0.004, P<.001).
CONCLUSIONS
Early adversity is associated with depressive symptoms through stress-related cognitive-affective pathways. Lower RSA may reflect diminished regulatory capacity that strengthens associations between ACEs and maladaptive cognitive-affective stress responses.
Sara Matovic, Justin Moase, L. Booij et al.· Biopsychosocial science and...· 0 citations
Abstract Objective NeoNatal Neurobehavioral Scale (NNNS-II) measures behavioral signs of stress according to systems, including the autonomic and central nervous systems. These systems influence heart rate variability (HRV), which is a biomarker for regulatory capacity. The present study aims to investigate whether patterns of autonomic dysregulation are evident in both behavioral and physiological measures. Study Design HRV metrics—short- and long-term fractal scaling exponents (α1, α2) and root mean square fluctuations (RMS1, RMS2)—were calculated from the heart rates of 51 preterm infants at 33 weeks postmenstrual age. The NNNS-II assessments were conducted at term-equivalent age. Results Linear regression revealed that higher total stress signs were associated with increased α2 ( β = 0.366, p = 0.006), indicating reduced long-scale autonomic complexity. Autonomic and central nervous systems–specific stress signs were significantly associated with elevated α2 ( β = 0.349, p = 0.022). Individual items such as high-frequency tremors were also associated with increased α2 ( β = 0.303, p = 0.018) whereas startles were not ( p = 0.096). Conclusion Neurobehavioral stress signs, particularly those associated with the central nervous system (CNS), are linked to early diminished autonomic variation in infants. These findings can help researchers and clinicians interpret the significance of neurobehavioral stress signs to autonomic tone in preterm infants. Key Points Neurobehavioral stress is linked to HRV. CNS stress predicts reduced autonomic complexity. Tremors were most strongly related to HRV.
Elan L Donnellan, J. Ngwa, N. Andescavage et al.· American Journal of Perinato...· 0 citations
Predictability, the degree to which environmental inputs are structured, patterned, and reliably signaled over time, has emerged as a central dimension of early experience with unique implications for brain development, stress physiology, and mental health. This review synthesizes convergent evidence from human and animal studies to argue that predictability is intrinsic to optimal brain development. Thus, unpredictable signals from the proximate environment—parents, family, and neighborhood—are a type of early-life adversity that is distinct from, for example, threat or deprivation. We first delineate what predictability means in developmental science, distinguishing it from valence and intensity. We then summarize multilevel mechanisms, from epigenomic regulation to circuit-level adaptions, by which predictable versus unpredictable signals shape developmental trajectories. We consider predictable structure against the backdrop of established types of early-life adversity, examining how resource scarcity, caregiver stress, and chaotic routines create unpredictable patterns that link to childhood and adult psychopathology. Building on conceptual and methodological work in human study cohorts and large populations as well as experimental animals, we discuss how to measure unpredictability (e.g., signal entropy, ecological assessments, questionnaires) and highlight sensitive windows when predictability is crucial for brain maturation. Finally, we propose paths for translational research and prevention of unpredictability-related sequelae on cognitive and mental health.
Mason Hardy, T. Baram· Annual Review of Development...· 0 citations
Anxiety and depression have been associated with worse performance on baseline balance and neurocognitive testing, and increased symptom reporting, using the SCAT, ImPACT, and BESS. This study replicated these findings using the Sway Sports+ Battery.
A sample of 10,885 middle/high school, and collegiate athletes, ages 13-22, completed a pre-season baseline assessment. The Sway Sports+ Battery contains a Balance module and yields Reaction Time, Inspection Time, Impulse Control, and Memory scores. Total Symptom scores were documented as well as Total Symptoms without Emotion (removing “Sadness”, “More Emotional”, “Irritability” and “Nervous or Anxious”). Athletes also completed a Patient Health Questionnaire (PHQ9) and Generalized Anxiety Disorder assessment (GAD7), and were assigned to groups based on their PHQ9 and GAD7 scores (Minimal: 0-4; Mild 5-9; Moderate-to-Severe 10+).
12.0% of athletes obtained GAD7 scores consistent with mild and 4.5% with moderate-to-severe anxiety; 13.3% of athletes obtained PHQ9 scores consistent with mild and 5.6% with moderate-to-severe depression. Athletes with moderate-to-severe anxiety scored significantly worse on Impulse Control (p<.001, Effect Size (ES)=.01) and Inspection Time (p<.001; ES=.01), and the three groups were significantly different with respect to endorsement of Total Symptoms (p<.001; ES=.20) and Total Symptoms without Emotion (p<.001; ES=.16), with small effect sizes. A similar pattern was obtained for PHQ9 scores, although Memory scores were also significant (p<.001; ES=.01). There were no significant differences on Balance performance.
Anxiety and depression is not related to decreased balance performance, but athletes with anxiety and depression perform worse on baseline cognitive testing using Sway, and endorse significantly more concussion-related symptoms.
Exercise intolerance, defined as the exacerbation of neurobehavioral symptoms during physical exertion, is commonly associated with the acute recovery phase after a mild traumatic brain injury (mTBI). However, Repetitive Head Trauma-Associated Persistent Exercise Intolerance (RHT-PEI) in individuals with remote, repetitive mTBIs has not been characterized.
P. Schatz, A. Wexler· Archives of Clinical Neurops...· 0 citations
