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

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

Goal disturbance in early-stage breast cancer survivors.

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.

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

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

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.

Cultivating a healthy neuro-immune network: A health psychology approach.

The field of psychoneuroimmunology (PNI) examines interactions among psychological and behavioral states, the brain, and the immune system. Research in PNI has elegantly documented effects of stress at multiple levels of the neuro-immune network, with profound implications for both physical and mental health. In this review, we consider how the neuro-immune network might be influenced by "positive" psychological and behavioral states, focusing on positive affect, eudaimonic well-being, physical activity, and sleep. There is compelling evidence that these positive states and behaviors are associated with changes in immune activity in the body, including reductions in peripheral inflammatory processes relevant for physical health. Growing evidence from animal models also suggests effects of positive states on immune cells in the brain and the blood-brain barrier, which then impact critical aspects of mood, cognition, and behavior. Tremendous advances are being made in our understanding of neuro-immune dynamics; one of the central goals of this review is to highlight recent preclinical research in this area and consider how we can leverage these findings to investigate and cultivate a healthy neuro-immune network in humans.

Inflammation and dimensions of reward processing following exposure to the influenza vaccine.

BACKGROUND: Alterations 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. METHODS: The 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. RESULTS: The influenza vaccine led to mild but significant increases in circulating levels of the pro-inflammatory cytokine interleukin-6 (IL-6) (p < .001). Consistent with hypotheses, increases in IL-6 predicted lower reward motivation (p = .029). However, contrary to hypotheses, increases in IL-6 predicted increased performance on a reward learning task (p = .043) and were not associated with changes in reward sensitivity (p's > .288). CONCLUSIONS: These 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.