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Although stress is often related to substance use, it remains unclear whether substance use is related to individual differences in how adolescents respond to stress. Therefore the present study examined associations between substance use and daily emotional reactivity to stress within a year across adolescence. Adolescents (N = 330; Mage = 16.40, SD = 0.74 at study entry; n = 186 female; n = 138 Latine; n = 101 European American; n = 72 Asian American; n = 19 identifying as another ethnicity including African American and Middle Eastern) completed a longitudinal study, including three assessments between the 10th grade and 3-years post-high school. At each assessment, participants reported frequency of alcohol and cannabis use and the number of substances they had ever used. They also completed 15 daily checklists, in which they reported the number of daily arguments and their daily emotion. Multilevel models suggested that more frequent alcohol and cannabis use were related to attenuated positive emotional reactivity to daily stress (i.e., smaller declines in positive emotion on days when they experienced more arguments) for both male and female adolescents. Associations for negative emotional reactivity to stress varied by sex; more frequent alcohol use and use of more substances in one's lifetime were related to greater anxious emotional reactivity to stress among female adolescents, whereas more frequent alcohol and cannabis use and higher lifetime substance use were related to attenuated depressive emotional reactivity to stress among male adolescents. Taken together, substance use was related to emotional reactivity to daily stress within the same year during adolescence, although associations differed by valence and adolescent sex.

Emotion reactivity refers to the intensity of changes in positive and negative emotion following a stimulus, typically studied with respect to daily stressors (e.g., arguments, demands) or laboratory stressors, including the Trier Social Stress Test (TSST). Yet, it is unclear whether emotion reactivity to daily and to laboratory stressors are related. The present study examined whether greater emotion reactivity to daily stressors (i.e., arguments, demands) is associated with greater reactivity to the TSST. Late adolescents (N = 82; Mage  = 18.35, SD = 0.51, range 17-19; 56.1% female; 65.9% Latine, 34.2% European American) reported whether they experienced arguments and demands with friends, family, and individuals at school and their negative and positive emotion nightly for 15 days. They also completed the TSST, a validated paradigm for eliciting social-evaluative threat, and reported their emotion at baseline and immediately post-TSST. Multilevel models examined whether daily and laboratory emotion reactivity were related by testing whether the daily associations between arguments and demands with emotion differed by emotion reactivity to the TSST. Individuals with greater positive emotion reactivity (i.e., greater reductions in positive emotion) and greater negative emotion reactivity to the TSST showed greater positive emotion reactivity to daily demands. Emotion reactivity to the TSST was not significantly related to emotion reactivity to arguments. Findings provide preliminary evidence that emotion reactivity to the TSST relates to some aspects of daily emotion reactivity, with relations differing depending on type of daily stressor and valence of emotion. Results contextualise the implications of emotion reactivity to the TSST for daily stress processes.

Online interventions that elicit kindness may enhance well-being. We tested the efficacy of three kindness interventions among breast cancer survivors. Participants (N = 137, M age = 62.65 years) were randomized to perform acts of kindness for others, acts of kindness for self, self-kindness meditation, or a daily-activities-writing control and completed three activities each week for 4 weeks. Primary (well-being, depressive symptoms) and secondary outcomes (social support, self-kindness) were assessed pre- and post-intervention. No differences emerged in the primary outcomes. However, relative to controls, participants in the acts of kindness to others condition reported greater increases in social support, and participants in the self-kindness meditation condition reported greater decreases in self-kindness. Among breast cancer survivors, performing prosocial acts may enhance feelings of social support. The two self-kindness conditions yielded either null or detrimental effects, suggesting that further research is needed on best practices for conducting self-focused kindness interventions.

ObjectiveResearch has established links between social isolation and heightened levels of proinflammatory cytokines (e.g., interleukin-6 [IL-6], tumour necrosis factor alpha [TNF-α]). Recent advances allow for the examination of cytokines that may also play a role in antiviral immunity (interferon-gamma [IFN-γ]). The present work explored how various features of social experience relate to circulating cytokines in breast cancer survivors, as inflammation has been tied to cancer recurrence and mortality.DesignFemale breast cancer survivors (N = 43) completed a blood draw to assess circulating levels of proinflammatory cytokines (IL-6, TNF-α) and levels of a cytokine that also relates to antiviral immunity (IFN-γ).Main outcome measuresWe examined associations between cytokines and different aspects of social experience, including household size, psychosocial well-being, and social threat anxiety.ResultsCirculating levels of IFN-γ were associated with larger household size (r = 0.32, p = 0.04) and higher levels of psychosocial well-being (r = 0.33, p = 0.04). Additionally, heightened levels of IL-6 were associated with social threat anxiety (r = 0.38, p = 0.01). Heightened IL-6 was also associated with household size (r = 0.33, p = 0.03).ConclusionThese findings are consistent with work suggesting that antiviral immunity and inflammation may have distinct contributions to the links between social experience and health, particularly for those previously diagnosed with breast cancer.

BackgroundEarly-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.MethodsParents 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.ResultsRelative 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.ConclusionsResults 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.

BackgroundThe Pathways to Wellness trial tested the efficacy of 2 interventions for younger breast cancer survivors: mindful awareness practices (MAPs) and survivorship education (SE). This planned secondary analysis examines intervention effects on stress, positive psychological outcomes, and inflammation (Clincaltrials.gov NCT03025139).MethodsWomen diagnosed with breast cancer at or before age 50 years who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments conducted at pre- and postintervention and at 3- and 6-month follow-up measured general stress perceptions, cancer-related intrusive thoughts and worry, positive affect, meaning and peace in life, altruism and empathy, and markers of inflammation. Analyses compared change in outcomes over time in each intervention group relative to WLC using linear mixed models.ResultsA total 247 women were randomly assigned to MAPs (n = 85), SE (n = 81), or WLC (n = 81). MAPs statistically significantly decreased intrusive thoughts and worry at postintervention and 3-month follow-up relative to WLC (P

Socioeconomic status has been related to poorer eating behaviors, potentially due to feeling of lower status relative to peers. Despite experimental evidence that temporarily feeling of lower status can contribute to greater caloric intake, it remains unclear how feeling of lower social status relate to eating behavior in daily life. This study aimed to test whether lower subjective social status (SSS)-the feeling of having relatively lower social status-in American society and relative to college peers were related to daily food selection. A sample of 131 young adults (Mage = 20.3, SD = 0.8; 60% female; 46% Latinos; 34% European American; 15% Asian American; 5% of other ethnicities) reported their SSS in society and in college and completed 15 daily reports regarding the number of daily servings they had of fruits, vegetables, fried foods, fast foods, desserts, and sugary drinks. Multilevel models with days nested within individuals were used to test whether low SSS in society or college related to daily food intake. Next, we examined whether associations were driven by young adults' perceived stress and daily stressors. Analyses controlled for age, gender, ethnicity, family and personal income, and parents' education to test the unique associations between subjective status and food intake. Whereas SSS in society was not related to food intake, young adults with lower SSS in their college consumed fewer daily servings of healthy foods and more daily servings of high-fat/high-sugar foods. Although lower college SSS was related to greater perceived stress, perceived stress and daily stressors were consistently unrelated to daily food intake. Findings suggested that lower SSS in local environments (e.g., college) may impact young adults' daily food choices through processes beyond heightened stress.

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.

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.

BackgroundInflammation 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.MethodsA 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).ResultsPatients 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.ConclusionsChemotherapy 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.

A growing body of evidence indicates that patients with cancer who receive cytotoxic treatments (such as chemotherapy or radiotherapy) have an increased risk of accelerated physical and cognitive ageing. Furthermore, accelerated biological ageing is a suspected driving force behind many of these observed effects. In this Review, we describe the mechanisms of biological ageing and how they apply to patients with cancer. We highlight the important role of specific behavioural factors, namely stress, sleep and lifestyle-related factors such as physical activity, weight management, diet and substance use, in the accelerated ageing of patients with cancer and cancer survivors. We also present a framework of how modifiable behaviours could operate to either increase the risk of accelerated ageing, provide protection, or promote resilience at both the biological level and in terms of patient-reported outcomes.

Contemporary breast cancer surgical procedures vary greatly by the amount of tissue removed, anesthesia time, and reconstruction. Despite historical literature comparing the health-related quality of life (HRQOL) after lumpectomy and mastectomy, HRQOL data are limited regarding contemporary surgical procedures. Further, biological processes (e.g., inflammation) associated with HRQOL outcomes have not been described. We conducted two studies to examine differences in post-operative physical and mental functioning, pain, fatigue, and systemic inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) in women with early-stage breast cancer. Study 1 assessed women before and after surgery (n = 27) and Study 2 used a large cross-sectional sample (n = 240) to confirm findings from Study 1 and included a no-surgery comparison group. In Study 1, women who received mastectomy had lower physical functioning than lumpectomy (ps

Hypothalamic pituitary adrenal gland (HPA) axis functioning has been linked with daily demands during adolescence. A ubiquitous, yet understudied daily demand in the lives of youth is the commute to school, which may be associated with the diurnal rhythm of cortisol as demonstrated in prior research among adults. The current study hypothesized that longer school commute times would be associated with altered HPA axis functioning as demonstrated by a heightened cortisol awakening response (CAR) and flatter diurnal slope. Additionally, given that the HPA axis follows a diurnal rhythm and adolescence is marked by changes in the circadian rhythm, adolescents with a more evening chronotype were hypothesized to evince even more altered HPA axis functioning in the face of long school commute times. A total of 269 adolescents (M = 16.38 years, SD = 0.74) provided saliva samples at wake, 15-min. post-wake, and 30-min. post-wake for the calculation of CAR and at dinnertime and bedtime for the calculation of diurnal slope, completed up to 8 nights of sleep actigraphy, and self-reported school commute time. Results suggest that more evening chronotype youth with longer school commute times evince a higher CAR, but not an altered diurnal slope. The present findings may have implications for adolescent mental health as higher CAR has been associated poor mental health and heightened stress.

PurposeYounger women are at risk for depression and related symptoms following breast cancer. The Pathways to Wellness study, a randomized, multi-institution, three-arm trial, tested the efficacy of two behavioral interventions for younger breast cancer survivors with elevated depressive symptoms: mindful awareness practices (MAPs) and survivorship education (SE) (Clincaltrials.gov identifier: NCT03025139).MethodsWomen diagnosed with breast cancer at or before 50 years of age who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments were conducted preintervention and postintervention and at 3-month and 6-month postintervention follow-ups. Analyses compared each intervention to WLC using linear mixed models. The primary outcome was change in depressive symptoms from preintervention to postintervention on the Center for Epidemiologic Studies-Depression Scale; secondary outcomes included change in fatigue, insomnia, and vasomotor symptoms.ResultsTwo hundred forty-seven women (median age = 46 years) were randomly assigned to MAPs (n = 85), SE (n = 81), or WLC (n = 81). MAPs and SE led to significant decreases in depressive symptoms from preintervention to postintervention relative to WLC (mean change relative to WLC [95% CI]: MAPs, -4.7 [-7.5 to -1.9]; SE, -4.0 [-6.9 to -1.1]), which persisted at 6-month follow-up for MAPs (mean change relative to WLC [95% CI]: MAPs, -3.7 [-6.6 to -0.8]; SE, -2.8 [-5.9 to 0.2]). MAPs, but not SE, also had beneficial effects on fatigue, insomnia, and vasomotor symptoms that persisted at 6-month follow-up (P < .05).ConclusionMindfulness meditation and SE reduced depressive symptoms in younger breast cancer survivors. These interventions can be widely disseminated over virtual platforms and have significant potential benefit for quality of life and overall survivorship in this vulnerable group.

BackgroundMajor cancer organizations recommend depression screening in patients and survivors. The 9-item Patient Health Questionnaire (PHQ-9) is often suggested, with limited information about its use.MethodsEnrollment data collected from younger breast cancer survivors participating in a behavioral intervention trial were used to examine the relationship between PHQ-9 scores (range = 0-27), patient characteristics, and responses to standardized psychosocial assessment tools. Major depressive disorder criterion was met if responses to the first 2 PHQ-9 items (range = 0-6) were 3 or greater. The sample was categorized by total PHQ-9 scores: less than 5 (minimal depressive symptoms), 5-9 (mild to moderate depressive symptoms), and 10 or greater (moderate to severe depression). PHQ-9 category associations with medical, demographic, psychosocial, and behavioral characteristics were examined using analysis of variance for continuous variables and χ2 tests for categorical variables.ResultsA total of 231 women met the study prescreening eligibility criterion of mild depressive symptoms and enrolled in the study. On average, they were 45.2 years old and 2.6 years since diagnosis. At enrollment, 22.1% met the screening criterion for possible major depressive disorder; among those with PHQ-9 scores of 10 or greater, 58.3% met this criterion. Anxiety, fatigue, insomnia, and intrusive thoughts about cancer were frequent and were associated with depressive symptom severity (all P < .001). In contrast, neither demographic nor cancer treatment characteristics were associated with depressive symptoms.ConclusionsDepressive symptoms in this selected sample of younger breast cancer survivors were independent of demographic characteristics or cancer treatment history, suggesting that depression screening is necessary to detect uncontrolled depressive symptoms.

BackgroundMajor cancer organizations recommend depression screening in patients and survivors. The 9-item Patient Health Questionnaire (PHQ-9) is often suggested, with limited information about its use.MethodsEnrollment data collected from younger breast cancer survivors participating in a behavioral intervention trial were used to examine the relationship between PHQ-9 scores (range = 0-27), patient characteristics, and responses to standardized psychosocial assessment tools. Major depressive disorder criterion was met if responses to the first 2 PHQ-9 items (range = 0-6) were 3 or greater. The sample was categorized by total PHQ-9 scores: less than 5 (minimal depressive symptoms), 5-9 (mild to moderate depressive symptoms), and 10 or greater (moderate to severe depression). PHQ-9 category associations with medical, demographic, psychosocial, and behavioral characteristics were examined using analysis of variance for continuous variables and χ2 tests for categorical variables.ResultsA total of 231 women met the study prescreening eligibility criterion of mild depressive symptoms and enrolled in the study. On average, they were 45.2 years old and 2.6 years since diagnosis. At enrollment, 22.1% met the screening criterion for possible major depressive disorder; among those with PHQ-9 scores of 10 or greater, 58.3% met this criterion. Anxiety, fatigue, insomnia, and intrusive thoughts about cancer were frequent and were associated with depressive symptom severity (all P < .001). In contrast, neither demographic nor cancer treatment characteristics were associated with depressive symptoms.ConclusionsDepressive symptoms in this selected sample of younger breast cancer survivors were independent of demographic characteristics or cancer treatment history, suggesting that depression screening is necessary to detect uncontrolled depressive symptoms.

BackgroundStress 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.MethodsWomen 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.ResultsStress 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 (β = 0.080, p = .002) and perceived stress (β = 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

BackgroundThe 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.MethodsTwenty-one young, healthy individuals were recruited to receive the annual influenza vaccine. Serial blood samples were collected immediately before, and 24, 48, and 72 ​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.ResultsSignificant elevations in IL-6 were observed at 24 ​h post-vaccination (mean increase ​= ​0.70 ​pg/mL, Cohen's d ​= ​0.54, p ​= ​.018)), with 61.9% of participants exhibiting peak concentrations at that time point, χ 2  ​= ​22.54, p ​

BackgroundFatigue is a common and expected side effect of cancer treatment. However, the majority of studies to date have focused on average levels of fatigue, which may obscure important individual differences in the severity and course of fatigue over time. The current study was designed to identify distinct trajectories of fatigue from diagnosis into survivorship in a longitudinal study of women with early-stage breast cancer.MethodsWomen with stage 0 to stage IIIA breast cancer (270 women) were recruited before (neo)adjuvant therapy with radiotherapy, chemotherapy, and/or endocrine therapy and completed assessments at baseline; posttreatment; and at 6 months, 12 months, and 18 months of follow-up. Growth mixture modeling was used to identify trajectories of fatigue, and differences among the trajectory groups with regard to demographic, medical, and psychosocial variables were examined.ResultsFive distinct trajectories of fatigue were identified: Stable Low (66%), with low levels of fatigue across assessments; Stable High (13%), with high fatigue across assessments; Decreasing (4%), with high fatigue at baseline that resolved over time; Increasing (9%), with low fatigue at baseline that increased over time; and Reactive (8%), with increased fatigue after treatment that resolved over time. Both psychological and treatment-related factors were found to be associated with fatigue trajectories, with psychological factors most strongly linked to high fatigue at the beginning of and over the course of treatment.ConclusionsThere is considerable variability in the experience of fatigue among women with early-stage breast cancer. Although the majority of women report relatively low fatigue, those with a history of depression and elevated psychological distress may be at risk of more severe and persistent fatigue.

ObjectiveCognitive difficulties are a common complaint among patients with breast cancer and may adversely affect psychological well-being. In particular, problems with executive functioning (EF) may interfere with coping, which is known to influence depressive symptoms. The current study was designed to examine correlations between EF, coping, and depressive symptoms in breast cancer survivors and to longitudinally test the hypothesis that coping mediates the relationship between EF and depressive symptoms.MethodsParticipants included 171 women with early-stage breast cancer assessed at the end of primary treatment with surgery, radiation, and/or chemotherapy and at 6 months, 1 year, and 2 years after treatment follow-ups as part of the Mind-Body Study. Participants completed questionnaires to assess subjective EF, approach and avoidant coping, and depressive symptoms, and neuropsychological testing was conducted to assess objective EF. Bivariate correlations were used to examine associations between EF, coping, and depressive symptoms. Mediation analyses were conducted using a bootstrapping approach (PROCESS).ResultsAt 1 year after treatment, objective and subjective EFs were correlated with avoidant coping (r = -0.172 [p = .024] and r = 0.297 [p < .001], respectively). In longitudinal analyses, use of the avoidant strategy behavioral disengagement at 1 year mediated the association between objective (95% bootstrap confidence interval = -0.282 to -0.042) and subjective (95% bootstrap confidence interval = 0.020 to 0.254) EFs at 6 months and depressive symptoms at 2 years.ConclusionsThis study highlights how problems with EF during survivorship are associated with avoidant coping and depressive symptoms. Thus, these findings identify potential cognitive and affective targets for depression intervention in this population.

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 βs ranged from .06 to .08; all ps

This prospective longitudinal study of breast cancer survivors (n = 167) examined the association of apolipoprotein ε4 (APOE ε4) genotype with cognition and interactions with chemotherapy or endocrine therapy up to 6 years after treatment. In general, we found no effects of ε4 across timepoints and treatment exposures; post hoc analysis at 3-6 years suggested a trend towards worse cognition in the domains of attention and learning among ε4 carriers exposed to endocrine therapy. Further study is needed.

PurposeThis study investigated the extent to which multiple sleep dimensions are associated with inflammation during adolescents' transition to young adulthood, a developmental period when sleep difficulties and systemic inflammation levels are on the rise. Additionally, the moderating roles of socioeconomic status (SES) and ethnicity were explored.MethodsA total of 350 Asian American, Latino, and European American youth participated at two-year intervals in wave 1 (n = 316, Mage = 16.40), wave 2 (n = 248 including 34 new participants to refresh the sample, Mage = 18.31), and wave 3 (n = 180, Mage = 20.29). Sleep duration (weekday and weekend) and variability in duration (nightly and weekday/weekend) were obtained from eight nights of wrist actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index. Levels of C-reactive protein (CRP), a biomarker of systemic inflammation, were assayed from dried blood spots obtained from finger pricks.ResultsMultilevel models demonstrated that greater weekday/weekend sleep variability and worse sleep quality were associated with higher CRP; shorter weekend duration was associated with higher CRP only at younger ages. Shorter weekday duration was associated with higher CRP only among high-SES youth, whereas greater nightly variability was associated with higher CRP only among European American youth.ConclusionsAspects of poor sleep may contribute to the rise of CRP during adolescents' transition to young adulthood, especially in earlier years. In addition, some sleep-CRP associations may vary as a function of youth's SES and ethnicity.

Chronic inflammation in women diagnosed with breast cancer is critically linked with tumor progression, metastasis and survival. C-reactive protein (CRP)-a circulating marker of inflammation-is an important prognostic marker for cancer-related outcomes in breast cancer survivors (e.g. recurrence, fatigue). Psychological stress, which increases circulating markers of inflammation following sympathetic nervous system (SNS) activation, may modulate tumor-relevant inflammatory processes. However, little is known about neural mechanisms that might link stress and downstream SNS-initiated proinflammatory processes, such as elevated CRP. Past work suggests that threat-related neural regions, such as the amygdala, may be key in translating psychological stress into SNS activity and subsequent peripheral inflammation. Thus, we examined amygdala reactivity to socially threatening stimuli in association with perceived stress and plasma CRP levels to further elucidate neuro-immune pathways of social threat processing within breast cancer survivors (N = 37). Significant positive correlations were found between left amygdala reactivity in response to socially threatening stimuli (e.g. angry/fearful faces vs happy faces) and perceived stress in the previous month (r = 0.32, P = 0.025) and between left amygdala reactivity and CRP (r = 0.33, P = 0.025). This work builds on prior research implicating the amygdala as a key structure in crosstalk between threat-related neural circuitries and peripheral inflammation, particularly within cancer survivors.

BackgroundChildhood 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.MethodsWomen (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.ResultsBased 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.ConclusionsIn 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.

Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17-18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17-18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19-20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body's physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.

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.

BackgroundEarly 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.MethodsParticipants (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.ResultsELS 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.ConclusionsExposure 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.

Subjective social status (SSS) reflects one's perception of one's standing within society. SSS has been linked with health outcomes, over and above socioeconomic status, and is thought to influence health in part by shaping stress responsivity. To test this, the present study examined the links between SSS and psychological, hypothalamic-pituitary-adrenal (HPA) axis, and cardiovascular responsivity in a sample of 87 ethnically diverse late adolescents (Mage = 18.39 years). Participants rated their family's SSS while either in high school (n = 50) or 1 year afterward (n = 37). Participants completed the Trier Social Stress Task (TSST) and reported their fear during baseline and after task completion, provided six saliva samples throughout the task, and had their heart rate monitored continuously throughout the task. Multilevel models, with time points nested within participants, were conducted to assess reactivity and recovery for each outcome. Results indicated that lower SSS was associated with greater fear reactivity and faster rates of HPA axis reactivity and recovery to baseline. Regarding cardiovascular responses, no differences were observed with respect to heart rate. Lower SSS predicted increased respiratory sinus arrhythmia during the stress task only among participants who rated their SSS while in high school; no association was observed for those who rated SSS after high school. Results suggest that perceptions of one's family's standing in society can shape responses to stress and potentially broader health.HighlightsSubjective social status (SSS) was linked with differences in stress responsivity. Specifically, lower SSS was associated with greater increases in fear following an acute stressor and faster rates of cortisol reactivity and recovery. Adolescents with lower SSS in high school showed less cardiovascular reactivity and recovery with respect to respiratory sinus arrhythmia, a marker of parasympathetic nervous system activity.

BackgroundAnhedonia, or loss of interest or pleasure, is a feature of depression and transdiagnostic construct in psychopathology. Theory and compelling evidence from preclinical models implicates stress-induced inflammation as a psychobiological pathway to anhedonic behavior; however, this pathway has not been tested in human models. Further, although anhedonia may reflect dysregulation in multiple dimensions of reward, the extent to which stress-induced inflammation alters these dimensions is unclear. Thus, the current experimental study used a standardized laboratory stressor task to elicit an inflammatory response and evaluate effects of stress-induced inflammation on multiple behavioral indices of reward processing.MethodsHealthy young women (age 18-25) completed behavioral reward tasks assessing reward learning, motivation, and sensitivity and were randomized to undergo an acute psychosocial stressor (n = 37) or a no-stress active control (n = 17). Tasks were re-administered 90-120 min post-stress to coincide with the peak of the stress-induced inflammatory response. Blood samples were collected for assessment of the pro-inflammatory cytokine interleukin-6 (IL-6) at baseline and 90 and 120 min post stressor.ResultsStress-induced IL-6 was associated with increased response bias during reward learning and increased motivation when probability of receiving a reward was low. Sensitivity to reward in the context of a motivation task was not altered in association with stress-induced IL-6.ConclusionsContrary to hypotheses, mild increases in IL-6 following acute stress were associated with increased reward responsiveness during reward learning and selective increases in motivation. Results contribute to an emerging and nuanced literature linking inflammation to reward processing, and demonstrate that behavioral effects of stress-induced inflammation may be detected in the laboratory setting.Clinical trial registrationNCT03828604.

The purpose of this study was to characterize the association between recent major life events and depressive symptoms during early adulthood, and to determine whether adolescents with chronically low positive affect or persistent sleep disturbance were more vulnerable to the link between stress and depressive symptoms. Adolescents (n = 147; 63.9% female; 33.7% non-Hispanic white) were recruited in 10th-11th grade and re-assessed 2 and 4 years later. At each assessment, adolescents completed measures of positive affect and sleep disturbances. At the final assessment, participants reported on their exposure to major life events in the past 12 months. Exposure to more major life events in the past year was associated with greater depressive symptoms in early adulthood. Chronically low positive affect and persistent sleep disturbances throughout adolescence each independently moderated this relationship. Specifically, only participants reporting low positive affect across the three assessments showed a positive and significant association between major life events and depressive symptoms. Further, only participants reporting sleep disturbances at all three assessments showed a positive and significant association between major life events and depressive symptoms. Chronically low positive affect and persistent sleep disturbances during adolescence may be useful indicators of risk for depression during early adulthood. Further, interventions targeting adolescent sleep disturbances and improving positive affect may be useful in reducing the risk for depression following life stress during this high risk developmental phase.

BackgroundRates of depression increase and peak during late adolescence and alterations in immune processes are thought to be both a risk factor and outcome of depression. However, few studies have examined depression-immune dynamics among adolescents. Using a functional genomics approach, the current study examined whether depressive symptoms were associated with activation of a gene expression profile, characterized by upregulated expression of pro-inflammatory-related genes and downregulated expression of antiviral-related genes in a sample of older adolescents (Mage = 18.37, SD = 0.51).MethodParticipants (n = 87) reported on their depressive symptoms during the past week using the CES-D, and provided blood samples for genome-wide transcriptional profiling of mRNA.ResultsAdolescents with clinically-significant levels of depressive symptoms (CES-D ≥ 16) exhibited upregulated expression of inflammation-related genes and downregulated expression of antiviral-related genes compared to their peers with lower levels of depressive symptoms (CES-D

ObjectivePoor sleep poses negative health consequences for youth, yet few longitudinal actigraphy studies have examined basic developmental trends in sleep across adolescents' transition to young adulthood. In this longitudinal actigraphy study, stability of individual differences and trajectories of sleep during and after high school were examined. The degree to which sleep trajectories differed by college attendance status was also studied.MethodsA total of 343 youth with Asian, Latino, and European American backgrounds completed eight days of wrist actigraphy at two-year intervals in Wave 1 (n = 295, Mage = 16.39), Wave 2 (n = 211 including 34 new participants to refresh the sample, Mage = 18.31), and Wave 3 (n = 144, Mage = 20.29). Sleep duration, efficiency, and latency were estimated for weekdays and weekends. Intra-individual variability in duration across nights was also obtained.ResultsSleep parameters were correlated modestly between Wave 1 and Wave 2, but not correlated between Wave 1 and Wave 3, indicating modest shorter-term and little longer-term stability of individual differences. Multilevel growth models demonstrated declines in weekday sleep duration and efficiency across high school and post-high school years. Intra-individual variability in duration increased over the years. Latency trajectories changed more for non-college attendees compared with college attendees.ConclusionsOverall the findings suggest developmental trends of worsening sleep during adolescents' transition to young adulthood. Interventions to improve sleep may need to target specific issues faced by youth at that particular period in their lives.

PURPOSE:Cancer-related goal disturbance can influence long-term outcomes in cancer patients and survivors; however, few studies have examined the factors that contribute to goal disturbance in early survivorship. DESIGN:The current study examined the relationships between demographic variables, cancer- and treatment-related factors, and behavioral and psychological symptoms (i.e., fatigue, pain, cognitive complaints, depressive symptoms, and anxiety) and goal disturbance in breast cancer survivors 1 year after treatment completion. METHODS:Women diagnosed with early-stage breast cancer (n = 171) completed assessments following primary treatment (i.e., surgery, radiation, and chemotherapy) and again 6 months and 1 year later. We focused on the 1-year post-treatment assessment when participants were asked if they had experienced a cancer-related goal disturbance. FINDINGS:Approximately, 27% of women reported a cancer-related goal disturbance. Analyses indicated that both receipt of chemotherapy and behavioral and psychological symptoms-analyzed as a composite score and individually-were associated with a higher probability of reporting a goal disturbance. CONCLUSIONS:Chemotherapy and behavioral and psychological symptoms were unique correlates of goal disturbance, suggesting that the impact of chemotherapy extends beyond its influence on persistent symptoms. IMPLICATIONS:Elucidating factors that inhibit the pursuit of meaningful activities in early survivorship is critically important to understanding the long-term psychosocial impacts of cancer diagnosis and treatment.

BACKGROUND:The conserved transcriptional response to adversity (CTRA), characterized by increased expression of proinflammatory genes and decreased expression of antiviral and antibody-related genes, is upregulated in the context of chronic adversity and distress and has been linked to cancer progression. Several studies suggest that the CTRA may also be down-regulated in association with some positive psychological states, particularly eudaimonic well-being. However, it is not clear if the link between inter-individual differences in the CTRA and eudaimonic well-being can be extended to intra-individual change. Using a standardized mindfulness-based intervention, the current study tested whether mindfulness-related increases in eudaimonic well-being related to intra-individual reduction in the CTRA in a sample of younger breast cancer survivors. METHODS:Participants were 22 women who had been diagnosed and treated for early-stage breast cancer at or before age 50 (Mage = 46.6 years) and had no evidence of active disease. Women completed self-report questionnaires and provided peripheral blood samples before and after a 6-week mindfulness meditation intervention. Regression analyses were used to quantify associations between the magnitude of change in eudaimonic well-being and the magnitude of change in the global CTRA score. RESULTS:Women reported significant increases in eudaimonic well-being and showed decreased expression of the pro-inflammatory subcomponent of the CTRA from pre- to post-intervention. The magnitude of increase in eudaimonic well-being was associated with the magnitude of decrease in the composite CTRA score, and this relationship was driven primarily by increased expression of the antiviral/antibody-related CTRA subcomponent. While the intervention was also associated with reduced depressive symptoms, there was no association between change in depressive symptoms and change in the overall CTRA composite score or either of its subcomponents. CONCLUSIONS:Results are consistent with the hypothesis that eudaimonic well-being may be an important mechanism in interventions aimed at enhancing health in vulnerable groups, and contribute to our understanding of how psychological well-being may influence physical health in cancer patients.

Psychosocial stress during childhood and adolescence is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis and with heightened inflammation, both of which are implicated in poor health; however, factors that may protect against these effects relatively early in life are not well understood. Thus, we examined whether psychosocial resources protect against stress-related alterations in the HPA axis and heightened inflammation in a sample of 91 late adolescents. Participants completed measures of various stressors (major life events, daily interpersonal stress, early adversity), and psychosocial resources (mastery, optimism, self-esteem, and positive reappraisal). They also completed the Trier Social Stress Test and provided saliva and blood samples for the assessment of cortisol and interleukin-6 reactivity. Each of the stressors was associated with lower cortisol reactivity. Additionally, associations with major life events and daily stress were moderated by psychological resources, such that more life events and daily stress were associated with decreased HPA reactivity among adolescents with lower levels of psychological resources, but not among those with higher levels of psychological resources. This pattern of findings was observed only for cortisol reactivity and not for interleukin-6 reactivity. Findings suggest that psychological resources may counteract the effects of certain adversity-related decreases in cortisol reactivity.

BackgroundPsychological stress and poor sleep are associated with a wide range of negative health outcomes, which are thought to be mediated in part by alterations in immune processes. However, the molecular bases of links among stress, sleep, and immune processes are not completely understood, particularly during adolescence when sensitivity to stress and problems with sleep tend to increase. In the current study, we investigated whether various stressors (daily stress, major life events, perceived stress), sleep indices (duration, efficiency), and their interactions (e.g., moderating effects) are associated with expression of genes bearing response elements for transcription factors that regulate inflammatory and anti-viral processes.MethodEighty-seven late adolescents completed daily checklists of their social experiences across a 15-day period and reported on their major life events during the previous year. They also completed actigraphy-based assessments of sleep quality and duration during 8 consecutive nights. An average of 5.5 months later, participants reported on their global perceptions of stress during the previous month and provided blood samples for genome-wide expression profiling of mRNA from peripheral blood mononuclear cells (PBMCs).ResultsHigher levels of daily interpersonal stress and shorter sleep duration were associated with upregulation of inflammation-related genes bearing response elements for proinflammatory transcription factor nuclear factor kappa B (NF-κB). Shorter sleep duration was also linked to downregulation of antiviral-related genes bearing response elements for interferon response factors (IRFs). Lastly, there was a significant interaction between daily stress and shorter sleep duration, such that the association between daily stress and inflammation-related gene expression was exacerbated in the context of shorter sleep duration. Results were independent of sex, ethnicity, parent education, body mass index, and smoking and alcohol history.ConclusionEveryday interpersonal stress and shortened sleep can be consequential for upstream NF-κB signaling pathways relevant to inflammatory processes during late adolescence. Notably, the occurrence of both may lead to even greater activation of NF-κB signaling.

BackgroundAlterations in reward processing are a central feature of depression and may be influenced by inflammation. Indeed, inflammation is associated with deficits in reward-related processes in animal models and with dysregulation in reward-related neural circuitry in humans. However, the downstream behavioral manifestations of such impairments are rarely examined in humans.MethodsThe influenza vaccination was used to elicit a mild inflammatory response in 41 healthy young adults (age range: 18-22, 30 female). Participants provided blood samples and completed behavioral measures of three key aspects of reward-reward motivation, reward learning, and reward sensitivity-before and 1 day after receiving the influenza vaccine.ResultsThe influenza vaccine led to mild but significant increases in circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) (p  .288).ConclusionsThese findings contribute to an emerging literature on the nuanced associations between inflammation and reward and demonstrate that even mild alterations in inflammation are associated with multiple facets of reward processing.

ObjectiveCardiovascular disease (CVD) is one of the most prevalent chronic conditions and leading causes of death. Although CVD clinically manifests in adulthood, underlying processes of CVD begin in the earlier decades of life. Inflammation has been shown to play a key role, but relatively little is understood about how inflammation changes over time among young individuals. Additionally, how psychosocial factors like stress may influence changes in inflammation earlier in the lifespan is not entirely clear. Thus, the current three-wave longitudinal study examined the developmental trajectory of CRP, a marker of systemic inflammation, over a 4-year period from mid-adolescence into young adulthood. Between- and within-person differences in stress in relation to changes in CRP were also examined.MethodA sample of 350 individuals was recruited during mid-adolescence and participated in 1 to 3 assessments, 2 years apart. At each assessment, participants provided dried blood spots for the assessment of CRP and reported on recent major life events, perceived stress, and daily interpersonal stress.ResultsMultilevel modeling indicated that CRP increased with age, and within-person increases in perceived stress, but not life events or daily stress, were associated with higher CRP. Between-person differences in average levels of stress from mid-adolescence into young adulthood were not associated with changes in CRP.ConclusionThese findings suggest that the link between stress and systemic inflammation between mid-adolescence and young adulthood may be most affected by contemporaneous experiences of perceived stress. There was little evidence to suggest that CRP trajectories varied by between-person differences in overall average levels of perceived stress, life events, and daily stress. (PsycINFO Database Record (c) 2019 APA, all rights reserved).