Background

Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals particularly vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms.

Methods

Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions.

Results

There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001).

Conclusion

The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment.

Limitation

BDNF genotype is an indirect measure of BDNF protein levels.

A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendationsfor how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.

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.

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.

Background and objectives

Chronic stress is implicated in many theories as a contributor to a wide range of physical and mental health problems. The current study describes the development of a chronic stress measure that was based on the UCLA Life Stress Interview (LSI) and adapted in collaboration with community partners for use in a large community health study of low-income, ethnically diverse parents of infants in the USA (Community Child Health Network [CCHN]). We describe the instrument, its purpose and adaptations, implementation, and results of a reliability study in a subsample of the larger study cohort.

Design and methods

Interviews with 272 mothers were included in the present study. Chronic stress was assessed using the CCHN LSI, an instrument designed for administration by trained community interviewers to assess four domains of chronic stress, each rated by interviewers.

Results

Significant correlations ranging from small to moderate in size between chronic stress scores on this measure, other measures of stress, biomarkers of allostatic load, and mental health provide initial evidence of construct and concurrent validity. Reliability data for interviewer ratings are also provided.

Conclusions

This relatively brief interview (15 minutes) is available for use and may be a valuable tool for researchers seeking to measure chronic stress reliably and validly in future studies with time constraints.