Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

The role of early life adversity and inflammation in stress-induced change in reward and risk processes among adolescents.

BACKGROUND: Early life adversity (ELA) has long been associated with increased risk for stress-related psychopathology, particularly depression. The neuroimmune network hypothesis posits that ELA increases sensitivity to psychosocial stress, moderating the association between increases in peripheral markers of inflammation and decreases in reward outcomes linked to anhedonia and risk-taking behaviors. The present study examined this hypothesis in a sample of adolescents by using acute psychosocial stress to probe the role of inflammatory signaling in behavioral measures of reward and risk processing. METHOD: 80 adolescents [13.86 years (SD = 1.54); 45 % female], oversampled for ELA, underwent the Trier Social Stress Test for Children while providing blood samples immediately before and 60-minutes after stress onset. Blood samples were assayed for plasma IL-6. One hour before stress onset, and then 60 min after, participants completed computer-administered behavioral tasks measuring reward (Pirate Task) and risk (Balloon Analog Risk Task). RESULTS: ELA moderated the association between increases in IL-6 and decreases in risk tolerance in pursuit of rewards (p = 0.003) and reward response bias (p = 0.04). Stress-induced increases in IL-6 were associated with decreases in pumps for rewards among adolescents exposed to high, relative to little or no, ELA. Further, greater IL-6 increases were associated with increases in bias toward high relative to low value rewards among adolescents with low adversity exposure but not among those exposed to higher adversity. CONCLUSIONS: The present study provides the first evidence in a pediatric sample that ELA may alter the role of stress-induced inflammation in reward and risk processing, and may extend our understanding of why stress leads to depression in this high-risk population.

Psychoneuroimmunology: An Introduction to Immune-to-Brain Communication and Its Implications for Clinical Psychology.

Research conducted over the past several decades has revolutionized our understanding of the role of the immune system in neural and psychological development and function across the life span. Our goal in this review is to introduce this dynamic area of research to a psychological audience and highlight its relevance for clinical psychology. We begin by introducing the basic physiology of immune-to-brain signaling and the neuroimmune network, focusing on inflammation. Drawing from preclinical and clinical research, we then examine effects of immune activation on key psychological domains, including positive and negative valence systems, social processes, cognition, and arousal (fatigue, sleep), as well as links with psychological disorders (depression, posttraumatic stress disorder, anxiety, schizophrenia). We also consider psychosocial stress as a critical modulator of neuroimmune activity and focus on early life adversity. Finally, we highlight psychosocial and mind-body interventions that influence the immune system and may promote neuroimmune resilience.

Psychosocial Resilience to Inflammation-Associated Depression: A Prospective Study of Breast-Cancer Survivors.

Stress can lead to depression, in part because of activation of inflammatory mechanisms. It is therefore critical to identify resilience factors that can buffer against these effects, but no research to date has evaluated whether psychosocial resilience mitigates the effects of stress on inflammation-associated depressive symptoms. We therefore examined psychosocial resources known to buffer against stress in a longitudinal study of women with breast cancer (N = 187). Depressive symptoms and inflammation were measured over a 2-year period extending from after diagnosis into survivorship. Cancer-related stress and psychosocial resources-social support, optimism, positive affect, mastery, self-esteem, and mindfulness-were measured after diagnosis. As hypothesized, women who reported having more psychosocial resources showed weaker associations between stress and depressive symptoms and weaker associations between stress and inflammation-related depressive symptoms. Results highlight the importance of psychosocial resilience by demonstrating a relationship between psychosocial resources and sensitivity to inflammation-associated depressive symptoms.

Socioeconomic Status and Inflammation in Women with Early-stage Breast Cancer: Mediation by Body Mass Index.

BACKGROUND: Breast cancer is the most common cancer among women in the US, and women of low socioeconomic status (SES) show markedly poorer outcomes than those of high SES. SES may influence health through inflammation, although links between SES and inflammatory biomarkers have not been investigated in women with breast cancer. This study tested the hypothesis that breast cancer patients of lower SES would show higher levels of inflammation than those of higher SES. BMI was examined as a mediator of this association. METHODS: Women recently diagnosed with early-stage breast cancer (N = 194) were recruited before neoadjuvant or adjuvant therapy. Participants completed questionnaires and provided blood samples for immune assessment. SES was indexed by participants' self-reported education and annual household income, BMI was determined by height and weight measurements, and blood was assayed for inflammatory biomarkers linked with cancer outcomes: IL-6, CRP, TNF-α, and sTNF-RII. General linear models tested associations between SES and inflammation, and mediation models examined indirect effects through BMI. RESULTS: Consistent with hypotheses, education status was associated with CRP, (F(2,185) = 4.72, p = 0.001), and sTNF-RII, (F(2,185) = 4.19, p = 0.02), such that lower education was associated with higher levels of both biomarkers. Further, BMI mediated the associations between education and CRP, (95% CIs [-0.62, -0.11; -0.76, -0.21]), sTNF-RII, (95% CIs [-0.09, -0.01; -0.10, -0.02]), and IL-6, (95% CIs [-0.32, -0.05; -0.38, -0.09]). Annual household income was not significantly associated with inflammation (ps > 0.25), and indirect effects on inflammation through BMI were not significant. CONCLUSIONS: Lower education was associated with higher levels of inflammation in this sample, which may presage poor breast cancer-related and clinical outcomes. SES should inform the development of interventions targeting BMI and inflammation in breast cancer.

The moderating role of gender in the association between quality of social relationships and sleep.

To determine whether the association between perceived social support or strain in close relationships and sleep outcomes varies by gender. Participants were selected from the Biomarker projects of either the MIDUS II or MIDUS Refresher study if they were in a married-or married-like relationship and shared a bed with their partner (N = 989). A subsample also participated in a seven-day sleep study (n = 282). Perceived social support and strain from partner, family, and friends were examined by self-report questionnaires. We used the Pittsburgh Sleep Quality Index, sleep daily diary, and actigraphy to measure both subjective and objective sleep. Social support and strain were both associated with sleep outcomes. Specifically, higher social support was associated with fewer daily reports of light sleep and feeling more rested in the morning, while higher social strain was associated with higher clinical sleep disturbance. For women, but not men, social support was significantly associated with lower daily sleep disturbance while perceived social strain was significantly associated with higher daily sleep disturbance, lighter sleep, feeling less rested in the morning, lower sleep efficiency, and longer sleep onset latency. Mainly among women, social support and strain are associated with an important transdiagnostic health outcome-sleep-which may have implications for a wide range of health disparities. Interpersonal stressors may increase health risks differently for women compared to men and one mechanism that may link social relationships to long-term health outcomes is sleep.

Early-life stress, depressive symptoms, and inflammation: the role of social factors.

OBJECTIVE: To identify modifiable, social factors that moderate the relationship between early-life stress (ELS) and health outcomes as measured by depressive symptoms and inflammation. METHODS: Data were from 3,416 adults (58.28% female), ages 36 - 97 (Mage = 68.41; SDage = 10.24) who participated in the 2006 wave of the Health and Retirement Study, a nationally representative sample of older adults in the United States. This study used hierarchical regression analyses to first test the main effects of ELS on depressive symptoms and inflammation (high-sensitivity C-reactive protein). Four social factors (perceived support, frequency of social contact, network size, and volunteer activity) were assessed as moderators of the ELS-depression and ELS-inflammation relationships. RESULTS: There was a small, positive association between ELS and depressive symptoms (B = 0.17, SE = 0.05, p = .002), which was moderated by social contact and perceived support. Specifically, ELS was only associated with elevated depressive symptoms for participants with limited social contact (B = 0.24, SE = 0.07, p < .001) and low perceived support (B = 0.24, SE = 0.07, p < .001). These associations remained after accounting for potential confounds (age, body-mass index, adulthood stress, and marital status). CONCLUSIONS: Increased social contact and perceived support may be protective for individuals at a higher risk of developing depressive symptoms as a result of ELS. Future interventions may benefit from leveraging these social factors to improve quality of life in adults with ELS.

Vulnerability to inflammation-related depressive symptoms: Moderation by stress in women with breast cancer.

BACKGROUND: Stress precipitates depression and may do so in part by increasing susceptibility to inflammation-induced depressive symptoms. However, this has not been examined among individuals facing a major life stressor. Accordingly, the present study tested the moderating role of stress on the longitudinal association between inflammation and depressive symptoms among women with breast cancer. METHODS: Women recently diagnosed with early-stage breast cancer (N = 187) were enrolled before starting adjuvant/neoadjuvant treatment. Blood draws and self-reported depressive symptoms were collected pre-treatment, post-treatment, and at 6, 12, and 18-month post-treatment follow ups. C-reactive protein (CRP) was used to index inflammation. Measures of psychological stress, including cancer-related stress, general stress perceptions, and childhood stress, were administered pre-treatment. RESULTS: Stress moderated the association between CRP and depressive symptoms, such that higher levels of CRP were associated with elevated depressive symptoms only among women who reported high cancer-related stress (ß = 0.080, p = .002) and perceived stress (ß = 0.053, p = .044); childhood stress effects were non-significant. Moreover, elevated CRP was associated with increased odds of exhibiting clinically significant depressive symptoms (OR = 1.64, p < .001) among women who reported high cancer-related stress. Results were independent of age, BMI, race and cancer-related covariates. CONCLUSIONS: Stress was found to heighten sensitivity to inflammation-associated depressive symptoms over a 2-year period, with notably stronger effects for subjective stress responses to a concurrent life event. Individuals who are most distressed following a major life event may exhibit the greatest risk for inflammation-induced depression.

Early life stress sensitizes youth to the influence of stress-induced cortisol on memory for affective words.

Early life stress (ELS) is a well-established risk factor for psychopathology across the lifespan. Cognitive vulnerability to stress-induced cortisol may explain risk and resilience. The current study aimed to elucidate a psychobiological pathway linking stress to altered memory for affective words among youth with and without exposure to ELS. One hundred and fifteen youth (ages 9-16, 47% female) were randomized either to a psychosocial stressor or a control condition. Immediately following the stress or control condition, participants completed a memory task for affective words. Change in salivary cortisol from immediately before to 25 min after stress onset were used to predict memory for affective words. Exposure to the acute laboratory stressor led to activation of the HPA axis. Greater cortisol reactivity was associated with less accurate recognition of negative valence words. Among youth exposed to ELS, greater cortisol reactivity to acute stress was associated with poorer recognition of dysphoric and neutral words. Acute increases in cortisol may interfere with negatively-valenced information processing that has implications for memory. Youth exposed to high ELS may be particularly vulnerable to the effects of cortisol, which may explain one pathway through which stress leads to psychopathology among at-risk youth.

Early life adversity exposure and circulating markers of inflammation in children and adolescents: A systematic review and meta-analysis.

This study provides a comprehensive review of the published research on the association between early life adversity and markers of inflammation in children and adolescents. We conducted a systematic review of the published literature on the association between early life adversity and markers of inflammation in pediatric populations. To date, 27 studies have been published in this area representing a wide range of global populations and diverse methods of which nearly half were prospective, longitudinal studies. Of these 27, only 12 studies shared an inflammatory outcome with 4 or more other studies; 9 for CRP, and 6 for IL-6. The association between early life adversity and both CRP, z = .07 [.04, .10], and IL-6, z = .17 [-.07, .42], were small and only significant for CRP although comparable in magnitude to the effects observed in adult samples. Descriptively, the association between early life adversity and CRP appeared to be stronger in studies conducted in infants and adolescents compared with middle childhood. There was minimal evidence of publication bias for studies measuring CRP, but evidence of publication bias for studies using IL-6. Eight studies have looked at the association between early life adversity and stimulated inflammatory cytokines in vitro, and both the methods and results of these studies were mixed; the majority observed exaggerated production of inflammatory cytokines despite mixed methodological approaches that make comparisons across studies difficult. In summary, the evidence supporting an association between early life adversity and inflammation in pediatric samples is limited so far by the number of studies and their heterogeneous methodological approaches. More research that is grounded in a developmental framework and informed by the complexity of the innate immune system is needed in this area.

Childhood maltreatment and monocyte gene expression among women with breast cancer.

BACKGROUND: Childhood adversity is reliably associated with immune alterations in adulthood, including increases in inflammatory processes. However, relatively few studies have investigated these associations in clinical populations such as cancer patients who are at risk for negative immune-related health outcomes. The current study tested the hypothesis that childhood maltreatment would be associated with alterations in immune-related gene expression in monocytes from women with breast cancer. METHODS: Women (n = 86) were recruited after diagnosis with early-stage breast cancer but before onset of adjuvant therapy with radiation, chemotherapy, and/or endocrine therapy. Participants completed questionnaires to assess childhood maltreatment (Childhood Trauma Questionnaire; CTQ) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D) and provided blood samples for immune assessment. CD14+ monocytes were isolated for RNA extraction and gene expression analyses. RESULTS: Based on responses to the CTQ, 28% of participants were classified as experiencing physical and/or emotional abuse or neglect and 7% as experiencing sexual abuse. Genome-wide transcriptional profiling of isolated monocytes identified 202 gene transcripts that differed in average expression level by > 25% over the range of maltreatment exposure. Bioinformatics analyses of those gene transcripts identified a significantly greater prevalence of NF-κB-binding motifs within the promoters of up-regulated vs. down-regulated genes (p = .028) in women exposed to childhood maltreatment, indicating greater inflammatory signaling. Parallel analyses of Type I interferon signaling also indicated greater prevalence of Interferon Response Factor (IRF)-related binding sites in women with a childhood maltreatment history (p = .020). Results remained significant in analyses controlling for current depression; however, NF-κB and IRF-related gene expression was higher in women with both maltreatment exposure and current depression. CONCLUSIONS: In women recently diagnosed with early-stage breast cancer, childhood maltreatment was associated with increases in the classical NF-kB-related pro-inflammatory signaling pathway and with increases in the Type I interferon system. These results suggest a broad pattern of chronic immunologic activation in breast cancer patients with a history of childhood maltreatment, particularly those who are currently experiencing clinically significant depressive symptoms. These findings have implications for the long-term health and well-being of maltreatment exposed breast cancer patients.

Early life stress sensitizes individuals to the psychological correlates of mild fluctuations in inflammation.

BACKGROUND: Early life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation. METHODS: Participants (ages 18-22; n = 41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7 days prior to and 7 days after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin-6 (IL-6) were measured immediately before and 24 hr after vaccination. RESULTS: ELS was not associated with the magnitude of change in IL-6 from pre- to post-vaccine, however, exposure to ELS moderated the association between change in IL-6 from pre- to post-vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL-6. CONCLUSIONS: Exposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed.

Acute sleep deprivation and the selective consolidation of emotional memories.

Research suggests that sleep preferentially consolidates the negative aspects of memories at the expense of the neutral aspects. However, the mechanisms by which sleep facilitates this emotional memory trade-off remain unknown. Although active processes associated with sleep-dependent memory consolidation have been proposed to underlie this effect, this trade-off may also be modulated by non-sleep-related processes, such as the circadian factors, stress-related factors, and/or mood congruent context effects involved in sleep deprivation. We sought to examine the potential role of these factors by randomizing 39 young adults into either a total sleep deprivation condition (26 consecutive hours awake) or a sleep condition (8 h sleep opportunity). Replicating the emotional memory trade-off effect, negative objects were better remembered than neutral objects or background images. However, in spite of generally worse memory performance (for neutral and background information), sleep-deprived participants showed similar recognition rates for negative emotional memories relative to participants who were given a full night of sleep.

Within-subject associations between inflammation and features of depression: Using the flu vaccine as a mild inflammatory stimulus.

BACKGROUND: Inflammation plays a role in mood and behavior that may be relevant to identifying risk factors and treatment for depression and other stress-related illnesses. The purpose of this study was to examine whether fluctuations in inflammation following a mild immune stimulus were associated with changes in daily reported features of depression for up to a week in a healthy sample of young adults. METHODS: Forty-one undergraduate students completed daily diaries of mood, feelings of social disconnection, sleep, and physical symptoms for one week before and after receiving the seasonal influenza vaccine. Circulating plasma interleukin-6 (IL-6) was measured via blood samples taken immediately before and one day after vaccination. RESULTS: There was a significant increase in circulating IL-6 from pre- to post-intervention (p = .008), and there was significant variability in the magnitude of IL-6 change. Greater increases in IL-6 were associated with greater mood disturbance on post-vaccine days, specifically depressed mood and cognitive symptoms. CONCLUSIONS: Minor increases in inflammation were associated with corresponding increases in features of depression, and these associations occurred in the absence of any physical symptoms. The influenza vaccine could be used to probe causal relationships with a high degree of ecological validity, even in high-risk and vulnerable populations, to better understand the role of inflammation in the pathogenesis of depression.

Predicting developmental changes in internalizing symptoms: examining the interplay between parenting and neuroendocrine stress reactivity.

In this study, we examined whether parenting and HPA-axis reactivity during middle childhood predicted increases in internalizing symptoms during the transition to adolescence, and whether HPA-axis reactivity mediated the impact of parenting on internalizing symptoms. The study included 65 children (35 boys) who were assessed at age 5, 7, and 11. Parenting behaviors were assessed via parent report at age 5 and 11. The child's HPA-axis reactivity was measured at age 7 via a stress task. Internalizing symptoms were measured via teacher reports at age 5 and 11. High maternal warmth at age 5 predicted lower internalizing symptoms at age 11. Also, high reported maternal warmth and induction predicted lower HPA-axis reactivity. Additionally, greater HPA-axis reactivity at age 7 was associated with greater increases in internalizing symptoms from age 5 to 11. Finally, the association between age 5 maternal warmth and age 11 internalizing symptoms was partially mediated by lower cortisol in response to the stress task. Thus, parenting behaviors in early development may influence the physiological stress response system and therefore buffer the development of internalizing symptoms during preadolescence when risk for disorder onset is high.

Childhood Maltreatment and Immune Cell Gene Regulation during Adolescence: Transcriptomics Highlight Non-Classical Monocytes.

Childhood maltreatment has been repeatedly linked to a higher incidence of health conditions with an underlying proinflammatory component, such as asthma, chronic obstructive pulmonary disease, stroke, and cardiovascular disease. Childhood maltreatment has also been linked to elevated systemic inflammation prior to the onset of disease. However, childhood maltreatment is highly comorbid with other risk factors which have also been linked to inflammation, namely major depression. The present analysis addresses this issue by assessing the association of maltreatment with genome-wide transcriptional profiling of immune cells collected from four orthogonal groups of adolescents (aged 13-17): maltreated and not maltreated in childhood, with and without major depressive disorder. Maltreatment and psychiatric history were determined using semi-structured clinical interviews and cross-validated using self-report questionnaires. Dried whole blood spots were collected from each participant (n = 133) and assayed to determine the extent to which maltreatment in childhood was associated with a higher prevalence of transcriptional activity among differentially expressed genes, specific immune cell subtypes, and up- or down-regulation of genes involved in immune function after accounting for current major depression. Maltreatment was associated with increased interferon regulatory factor (IRF) transcriptional activity (p = 0.03), as well as nuclear factor erythroid-2 related factor 1 (NRF1; p = 0.002) and MAF (p = 0.01) among up-regulated genes, and increased activity of nuclear factor kappa beta (NF-κB) among down-regulated genes (p = 0.01). Non-classical CD16+ monocytes were implicated in both the up- and down-regulated genes among maltreated adolescents. These data provide convergent evidence supporting the role of maltreatment in altering intracellular and molecular markers of immune function, as well as implicate monocyte/macrophage functions as mechanisms through which childhood maltreatment may shape lifelong immune development and function.

Protocol for teen inflammation glutamate emotion research (TIGER): Toward predictors of treatment response and clinical course in depressed adolescents.

Adolescent-onset depression is a prevalent and debilitating condition commonly associated with treatment refractory depression and non-response to first-line antidepressants. There are, however, no objective tests to determine who may or may not respond to antidepressants. As depressed adolescents are especially vulnerable to the lifelong consequences of ineffectively-treated depression, it is critical to identify neurobiological predictors of treatment non-response in this population. Here, we describe the scientific rationale and protocol for the Teen Inflammation Glutamate Emotion Research (TIGER) study, a prospective 18-month investigation of 160 depressed adolescents who will be assessed before and after treatment with selective serotonin reuptake inhibitors. TIGER will be using ultra-high field imaging to test the effects of acute stress and antidepressant treatment on inflammatory and glutamatergic processes hypothesized to underlie depression maintenance. Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression. ClinicalTrials.gov Identifier: NCT05329441.

Facial emotion expression recognition by children at familial risk for depression: high-risk boys are oversensitive to sadness.

BACKGROUND: Offspring of depressed parents are at greatly increased risk for mood disorders. Among potential mechanisms of risk, recent studies have focused on information processing anomalies, such as attention and memory biases, in the offspring of depressed parents. In this study we examined another information processing domain, perceptual sensitivity to emotion cues in facial expressions, as a potential mechanism of risk that characterizes the offspring of depressed parents. METHODS: The study included 64 children at familial-risk for depression and 40 low-risk peers between the ages 7 and 13(Mage = 9.51; SD = 2.27). Participants were presented with pictures of facial expressions that varied in emotional intensity from neutral to full-intensity sadness or anger (i.e., emotion recognition), or pictures of faces morphing from anger to sadness (emotion discrimination). After each picture was presented, children indicated whether the face showed a specific emotion (i.e., sadness, anger) or no emotion at all (neutral) using a forced choice paradigm. We examined group differences in the intensity of emotion that suggested greater sensitivity to specific emotions. RESULTS: In the emotion recognition task, boys (but not girls) at familial-risk for depression identified sadness at significantly lower levels of emotional intensity than did their low-risk peers. The high and low-risk groups did not differ with regard to identification of anger. In the emotion discrimination task, both groups displayed over-identification of sadness in ambiguous mixed faces but high-risk youth were less likely to show this labeling bias than their peers. CONCLUSION: Our findings are consistent with the hypothesis that enhanced perceptual sensitivity to subtle traces of sadness in facial expressions may be a potential mechanism of risk among boys at familial-risk for depression. This enhanced perceptual sensitivity does not appear to be due to biases in the labeling of ambiguous faces.

Predictors of Adolescent Resilience During the COVID-19 Pandemic in a Community Sample of Hispanic and Latinx Youth: Expressive Suppression and Social Support.

The COVID-19 pandemic has created unprecedented disruptions in the daily lives and mental health of adolescents. Less attention has been given to the psychosocial resources that may mitigate the impact of COVID-19 on adolescent mental health, particularly among minoritized populations. In the present study, 259 youth (aged 11-18) were recruited from a community center for integrated prevention and intervention services in a predominantly Latinx and Hispanic community. Youth completed questionnaires about the impact COVID-19 has had on their lives, psychosocial resources (humor, optimism, emotion regulation, social support), and psychiatric symptoms (depressive symptoms, anxiety symptoms, sleep disturbances, aggression). After accounting for age, sex, and exposure to early life adversity, higher reported COVID-19 impact was associated with more depressive symptoms, b = 6.37 (SE = 1.67), 95% CI [3.08, 9.66], p < 0.001, more anxiety symptoms, b = 9.97 (SE = 1.63), 95% CI [6.75, 13.18], p < 0.001, and more sleep disturbances, b = 1.24 (SE = 0.34), 95% CI [0.57, 1.91], p < 0.001. Youth that reported infrequent expressive suppression and the lowest scores on giving social support were at the greatest risk for aggressive behavior in the context of high COVID-19 impact, ps < 0.007. Increasing emotion regulation skills, such as expressive suppression, and opportunities to give social support may promote resilience among high risk youth in the context of this ongoing community stressor.

Enhanced Immune Activation Following Acute Social Stress Among Adolescents With Early-Life Adversity.

Background: Early-life adversity (ELA) has been linked to higher depression risk across the life span and chronic inflammatory conditions that contribute to earlier mortality. In this study, we characterized innate immune responses to acute social stress in a community sample of adolescents (mean age = 13.9 ± 1.6 years; 46.4% female) as a potential pathway linking ELA and depression pathogenesis. Methods: Parents reported their child's exposure to 9 ELAs, and adolescents participated in the Trier Social Stress Test for Children, with blood collected immediately before and then at 60 and 90 minutes thereafter. Overall, 65 adolescents had complete data for analysis of stress-induced changes in gene expression and 84 adolescents had complete data for circulating inflammatory markers. Results: Relative to adolescents exposed to no ELA (11.9%) or low ELA (ELA = 1-3; 67.9%), those exposed to high ELA (ELA = 4+; 20.2%) showed larger stress-associated increases in expression of both proinflammatory and innate antiviral gene transcripts in circulating blood. Consistent with a potential mediating role of sympathetic nervous system activity, promoter-based bioinformatics analyses implicated CREB transcription factor activity in structuring observed gene expression differences. These effects were accompanied by a smaller initial but protracted increase in circulating interleukin 6 in adolescents with high ELA. Conclusions: Results are consistent with the hypothesis that ELA may enhance cellular and gene regulatory reactivity to stress, which may, in turn, increase vulnerability to depression and other inflammation-related disease processes.