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.

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.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

PURPOSE: To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories. METHODS: Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories. RESULTS: Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F = 4.13; p = 0.0006) and tangible (F = 2.86; p = 0.01) social support over time, was associated with recovery from depressive symptoms. CONCLUSIONS: Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

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.

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.

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.

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.

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.

Acute and Chronic Effects of Adjuvant Therapy on Inflammatory Markers in Breast Cancer Patients.

BACKGROUND: Inflammation contributes to poor behavioral, functional, and clinical outcomes in cancer survivors. We examined whether standard cancer treatments-radiation and chemotherapy-led to acute and persistent changes in circulating markers of inflammation in breast cancer patients. METHODS: A total of 192 women diagnosed with early stage breast cancer provided blood samples before and after completion of radiation and/or chemotherapy and at 6-, 12-, and 18-month posttreatment follow-ups. Samples were assayed for circulating inflammatory markers, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, downstream markers of their activity (soluble TNF receptor type II [sTNF-RII], C reactive protein), and other inflammatory mediators (IL-8, interferon-γ [IFN-γ]). Analyses evaluated within-group changes in inflammatory markers in 4 treatment groups: no radiation or chemotherapy (n = 39), radiation only (n = 77), chemotherapy only (n = 18), and chemotherapy with radiation (n = 58). RESULTS: Patients treated with chemotherapy showed statistically significant increases in circulating concentrations of TNF-α, sTNF-RII, IL-6, and IFN-γ from pre- to posttreatment, with parameter estimates in standard deviation units ranging from 0.55 to 1.20. Those who received chemotherapy with radiation also showed statistically significant increases in IL-8 over this period. Statistically significant increases in TNF-α, sTNF-RII, IL-6, IFN-γ, and IL-8 persisted at 6, 12, and 18 months posttreatment among patients treated with chemotherapy and radiation (all P < .05). Patients treated with radiation only showed a statistically significant increase in IL-8 at 18 months posttreatment; no increases in any markers were observed in patients treated with surgery only. CONCLUSIONS: Chemotherapy is associated with acute increases in systemic inflammation that persist for months after treatment completion in patients who also receive radiation therapy. These increases may contribute to common behavioral symptoms and other comorbidities in cancer survivors.

Younger women are more susceptible to inflammation: A longitudinal examination of the role of aging in inflammation and depressive symptoms.

BACKGROUND: The degree to which effects of inflammation on mood and behavior vary across the lifespan remains relatively unexplored despite well-established, age-related alterations in both the immune and central nervous systems. Further, the implications of this developmental process within different symptom domains warrants careful consideration. METHODS: Women diagnosed with breast cancer (n = 188; ages 27-89) provided blood samples and reported depressive symptoms prior to adjuvant treatment, at the end of adjuvant treatment, and 6-, 12-, and 18-months after completing adjuvant treatment via the CES-D. Blood was assayed for C-reactive Protein (CRP) and interleukin (IL)-6. We used mixed linear effect models to estimate within- and between-person effects of CRP or IL-6 on 4 domains of depressive symptoms: depressed affect, low positive affect, somatic complaints, and interpersonal problems. RESULTS: High average inflammation was associated with elevated somatic complaints (CRP p = .009, IL-6: p = .05), interpersonal problems (CRP p = .002, IL-6 p < .001), and positive affect (IL-6 p = .03), but only among the youngest women in the sample (age 50 or younger). Younger women also reported more depressed affect at assessments when inflammation was higher (CRP p = .045, IL-6 p = .09). CONCLUSIONS: The association between inflammation and specific depressive symptoms is dynamic and varies across the lifespan, which may help clarify apparent inconsistencies in the extant literature as well as inform more precise interventions targeting this pathway.

Women with lower systemic inflammation demonstrate steeper cognitive decline with age: Results from a large prospective, longitudinal sample.

Background: Men and women experience large disparities in prevalence, detection, and clinical course of neurodegenerative diseases. Inflammation has been implicated in the pathogenesis of neurodegenerative diseases, yet there is a paucity of literature documenting sex differences in this phenomenon in prospective, longitudinal studies. Methods: Participants were 4217 non-smoking individuals (62.2% female; aged 46-91 at enrollment) enrolled in the Health and Retirement Study who provided dried blood spots and completed a standardized assessment of cognitive function 3 times across 8 years. Inflammation was indexed using C-reactive protein (CRP). Results: Higher CRP was associated with lower concurrent cognitive function, b = -0.13 (SE = 0.06), p < .05, but less decline in cognitive function over time, b = 0.02 (SE = 0.01), p < .05. Sex moderated the association between CRP and decline in total cognitive function, b = 0.02 (SE = 0.01), p < .05, such that the steepest declines in cognitive function were observed among women with the lowest CRP concentrations. Conclusions: Women with lower systemic inflammation as measured by CRP may be at risk of going undetected for neurodegenerative disease, especially given their overall higher cognitive scores. This may perpetuate sex-related disparities in prevention and clinical course. Attention to the underlying biological mechanisms explaining the link between lower CRP and risk for cognitive decline for women and its potential clinical implications are needed.

Psychoneuroimmunology in the time of COVID-19: Why neuro-immune interactions matter for mental and physical health.

The brain and immune system are intricately connected, and perturbations in one system have direct effects on the other. This review focuses on these dynamic psychoneuroimmune interactions and their implications for mental and physical health in the context of the COVID-19 pandemic. In particular, we describe how psychological states influence antiviral immunity and the vaccine response, and how immune changes triggered by COVID (either via infection with SARS-CoV-2 or associated stressors) can influence the brain with effects on cognition, emotion, and behavior. We consider negative psychological states, which have been the primary focus of psychological research in the context of COVID-19 (and psychoneuroimmunology more generally). We also consider positive psychological states, including positive affect and eudaimonic well-being, given increasing evidence for their importance as modulators of immunity. We finish with a discussion of interventions that may be effective in improving immune function, the neuro-immune axis, and ultimately, mental and physical health.

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.

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.

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.

Moderators of inflammation-related depression: a prospective study of breast cancer survivors.

Inflammation has been shown to predict depression, but sensitivity to inflammation varies across individuals. Experimental studies administering potent pro-inflammatory agents have begun to characterize this sensitivity. However, risk factors for inflammation-associated depression in naturalistic contexts have not been determined. The present study examined key psychological and behavioral risk factors (state anxiety, perceived stress, negative affect, disturbed sleep, and childhood adversity) as potential moderators of the relationship between inflammation and depressive symptoms in a prospective longitudinal study of breast cancer survivors. Women with early stage breast cancer were recruited after completing primary cancer treatment (nfinal = 161). Depressive symptoms, inflammatory markers (CRP, IL-6, and sTNF-RII), and key risk factors were assessed post treatment (T1), at 6 and 12-month follow-ups (T2 and T3), and during a final follow-up (TF) 3-6 years after T1; childhood adversity was measured only at T3. Inflammatory markers were combined into a single inflammatory index prior to analyses. Women who reported higher levels of state anxiety, perceived stress, negative affect, and/or sleep disturbance at T1 (post-treatment) exhibited higher depressive symptoms at times when inflammation was higher than typical (interaction ßs ranged from .06 to .08; all ps < .014). Results demonstrate the relevance of these risk factors for understanding inflammation-associated depression in a clinical context and could inform targeted strategies for prevention and treatment among at-risk populations.

Using the influenza vaccine as a mild, exogenous inflammatory challenge: When does inflammation peak?

BACKGROUND: The influenza vaccine has shown promise as a mild, exogenous inflammatory challenge, but use of this model is limited by lack of knowledge about the timing of the inflammatory response. This study was designed to characterize the time-course of the acute inflammatory response and explore psychological and behavioral predictors of that response. METHODS: Twenty-one young, healthy individuals were recruited to receive the annual influenza vaccine. Serial blood samples were collected immediately before, and 24, 48, and 72 â€‹h following influenza vaccination. Interleukin (IL)-6 concentrations were assayed at each time-point and psychological and behavioral factors (anxiety and depressive symptoms, sleep disturbance, and childhood adversity) were assessed at baseline. RESULTS: Significant elevations in IL-6 were observed at 24 â€‹h post-vaccination (mean increase â€‹= â€‹0.70 â€‹pg/mL, Cohen's d â€‹= â€‹0.54, p â€‹= â€‹.018)), with 61.9% of participants exhibiting peak concentrations at that time point, χ 2  â€‹= â€‹22.54, p â€‹< â€‹.001, η â€‹= â€‹0.52. In exploratory analyses, sleep disturbance was associated with greater increases in IL-6 at 24 â€‹h. CONCLUSIONS: By identifying the peak IL-6 response to influenza vaccination among a sample of young, healthy individuals, these findings support the use of the influenza vaccine in future PNI research. This vaccine model can be used to examine the impact of mild inflammatory challenges on the brain and behavior, and to identify psychological and behavioral factors (e.g., anxiety, sleep) that modulate inflammatory reactivity.

Dysregulated arousal as a pathway linking childhood neglect and clinical sleep disturbances in adulthood.

BACKGROUND: A history of childhood maltreatment has a well-established association with clinical sleep disturbances in adulthood, which is a transdiagnostic contributor to many chronic diseases. OBJECTIVE: Determine whether actigraphy-measured indices of dysregulated arousal during sleep explain associations between abuse or neglect in childhood and clinical sleep disturbances in adulthood. PARTICIPANTS AND SETTING: Participants were 646 individuals, ages 25-83 (59.3% female) from the MIDUS II Biomarker, Refresher studies. METHODS: Participants completed the Childhood Trauma Questionnaire, wore an actigraph for seven days, and rated sleep quality using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Both neglect (b = 0.66, SE = 0.33, p = .04) and abuse (b = 1.09, SE = 0.32, p < .001) were associated with clinical sleep disturbance. Actigraphy-measured sleep efficiency mediated the link between neglect and clinical sleep disturbances (ab = 0.33, SE = 0.12, 95%CI [0.12, 0.57]). However, no such link between abuse and clinical sleep disturbances was mediated by actigraphy-measured indices. Sleep onset latency did not mediate the link between neglect or abuse and sleep disturbance. Models covaried for other maltreatment, gender, and age. CONCLUSIONS: While the unique associations between abuse or neglect and clinical sleep disturbances were robust in this sample, only sleep efficiency emerged as a mediator linking maltreatment and clinical sleep disturbances. Critically, this mediation was specific to neglect. Abuse and neglect may lead to disease through distinct pathways. Moreover, potential dysregulation in arousal that leads to sleep inefficiency may be a specific pathway through which experiences of neglect in childhood contribute to chronic disease.

Predictors of Adolescent Resilience During the COVID-19 Pandemic: Cognitive Reappraisal and Humor.

PURPOSE: The COVID-19 pandemic and efforts to slow the spread of disease have particularly affected the lives of adolescents. Many studies have recently identified the risks to adolescent mental health posed by the COVID-19 pandemic, yet few have identified the markers of resilience to the events and concerns associated with the pandemic's lived experience. This study examined the moderating role of psychosocial resources in the association between the tangible and emotional experiences of the COVID-19 pandemic and symptoms of common psychiatric problems during adolescence (depression, anxiety, proactive and reactive aggression, and sleep problems). METHODS: Participants were adolescents in the United States who were oversampled for early life adversity before the COVID-19 pandemic. The psychosocial resources assessed were humor styles, emotion regulation, social support, optimism, and purpose in life, which have previously been identified as protective in the acute aftermath of stressful events. RESULTS: Greater COVID-19 impact was associated with more anxiety, depressive symptoms, sleep disturbance, and proactive aggression. COVID-19 impact and psychiatric symptoms were unrelated among youth reporting high self-enhancing humor and cognitive reappraisal. CONCLUSIONS: Adolescents high in humor and cognitive reappraisal may be protected against the mental health correlates of the COVID-19 pandemic and other prolonged stressors. Importantly, these factors are known to be modifiable through behavioral interventions. Attention to their effectiveness in prevention and intervention studies is needed as the pandemic continues to exert its impact on individuals and society.