Heather M. Derry

Inflammation: Depression Fans the Flames and Feasts on the Heat

Depression and inflammation fuel one another. Inflammation plays a key role in depressions pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.

Lower subjective social status exaggerates interleukin-6 responses to a laboratory stressor.

Growing evidence suggests that lower subjective social status (SSS), which reflects where a person positions himself on a social ladder in relation to others, is independently related to poor health. People who rate themselves lower in status also experience more frequent stressors and report higher stress than those who rate themselves higher in status, and chronic stress can enhance an individuals response to subsequent stressors. To address whether SSS predicted stress-induced interleukin-6 (IL-6) changes, we assessed 138 healthy adults at rest and following the Trier Social Stress Test (TSST). Participants completed the TSST at two study visits, separated by 4 months. People who placed themselves lower on the social ladder had larger IL-6 responses from baseline to 45 min post-stressor (p=0.01) and from baseline to 2h post-stressor (p=0.03) than those who placed themselves higher on the social ladder. Based on a ratio of subjective threat and coping ratings of the stress task, participants who viewed themselves as lower in status also tended to rate the speech task as more threatening and less manageable than those who viewed themselves as higher in status (p=0.05). These data suggest that people with lower perceived status experience greater physiological and psychological burden from brief stressors compared to those with higher perceived status. Accordingly, responses to stressors may be a possible mechanistic link among SSS, stress, and health.

Yoga and self-reported cognitive problems in breast cancer survivors: a randomized controlled trial

Cancer survivors often report cognitive problems. Furthermore, decreases in physical activity typically occur over the course of cancer treatment. Although physical activity benefits cognitive function in noncancer populations, evidence linking physical activity to cognitive function in cancer survivors is limited. In our recent randomized controlled trial, breast cancer survivors who received a yoga intervention had lower fatigue and inflammation following the trial compared with a wait list control group. This secondary analysis of the parent trial addressed yogas impact on cognitive complaints.

Sex Differences in Depression: Does Inflammation Play a Role?

Women become depressed more frequently than men, a consistent pattern across cultures. Inflammation plays a key role in initiating depression among a subset of individuals, and depression also has inflammatory consequences. Notably, women experience higher levels of inflammation and greater autoimmune disease risk compared to men. In the current review, we explore the bidirectional relationship between inflammation and depression and describe how this link may be particularly relevant for women. Compared to men, women may be more vulnerable to inflammation-induced mood and behavior changes. For example, transient elevations in inflammation prompt greater feelings of loneliness and social disconnection for women than for men, which can contribute to the onset of depression. Women also appear to be disproportionately affected by several factors that elevate inflammation, including prior depression, somatic symptomatology, interpersonal stressors, childhood adversity, obesity, and physical inactivity. Relationship distress and obesity, both of which elevate depression risk, are also more strongly tied to inflammation for women than for men. Taken together, these findings suggest that women’s susceptibility to inflammation and its mood effects may contribute to sex differences in depression. Depression continues to be a leading cause of disability worldwide, with women experiencing greater risk than men. Due to the depression-inflammation connection, these patterns may promote additional health risks for women. Considering the impact of inflammation on women’s mental health may foster a better understanding of sex differences in depression, as well as the selection of effective depression treatments.

Telomere Length: A Marker of Disease Susceptibility?

Telomeres, the caps found at the ends of chromosomes, have clinical significance for health: a growing literature links shorter telomeres with depression, poor health behaviors, age-related diseases, and mortality (Epel et al., 2010; Lin et al., 2012). Elegant prior work by Cohen and his colleagues clearly demonstrated that psychological stress and socioeconomic status (SES) alter infectious disease risk (Cohen et al., 2013). In their newest paper, Cohen and colleagues show that adults with lower SES during childhood had shorter telomeres on CD8+CD28− T-cells and were more likely to develop the common cold than adults with a higher childhood SES (Cohen et al., in press). The authors argue that lower childhood SES speeds the progression to replicative senescence in CD8+CD28− T-cells, an important T-cell subset because of its role in cancer and viral illnesses; shorter CD8+CD28− telomeres reflect greater senescence (Cohen et al., in press). Accordingly, childhood SES could have a far-reaching impact on disease susceptibility. Inflammation may be one mechanism linking lower childhood SES to shortened telomeres; inflammation triggers T-cell proliferation, one known cause of telomere shortening (Kiecolt-Glaser et al., 2013). Indeed, converging evidence suggests that other forms of childhood adversity, such as abuse or neglect, are linked to elevated levels of inflammation and shortened telomeres. For example, adults who experienced more early life adversity had higher inflammation and shorter telomeres than adults who experienced less early life adversity (Kiecolt-Glaser et al., 2011). Importantly, Cohen’s paper suggests that early childhood stressors may affect immune function throughout the lifespan (Cohen et al., in press); related work has demonstrated that adult SES also has immune consequences, potentially because low SES adults report high levels of stress and depression (Jaremka et al., 2013). For instance, adults with lower subjective SES had stronger inflammatory responses to a laboratory speech task than those with higher subjective SES, and tended to rate the task as more threatening and less manageable (Derry et al., 2013). Taken together, previous research and the new Cohen paper suggest that low SES and early life stress elevate inflammation, thereby shortening telomeres and increasing infectious disease susceptibility during adulthood. Prior work investigating the links among SES, early life adversity, inflammation, and disease susceptibility often utilized relatively healthy adult samples. Indeed, Cohen and colleagues tested their hypotheses with a unique sample of extremely healthy adults (Cohen et al., in press); their volunteers were free from major medical comorbidities and were not taking medication other than birth control. Furthermore, their average age was 29.8, with a range from 18 to 55. The odds of needing prescription medication for one or more chronic conditions rise steeply during middle age, and thus their sample represents the very best case scenario in terms of physical and mental health. Although telomere attrition is an important correlate of aging, health status affects this relationship. For example, healthy centenarians had longer telomeres than centenarians who had two or more chronic health conditions (Terry et al., 2008). Accordingly, chronic illness may further accelerate age-related telomere shortening. Indeed, many chronic diseases, including cancer, have inflammatory correlates or consequences (Jaremka et al., 2013). In this context, elevated inflammation among cancer survivors carries clear risks for accelerated aging. The tissue damage resulting from surgery, chemotherapy, and radiation may evoke inflammatory responses and thus shorten telomeres. Furthermore, many people reduce physical activity and gain weight during cancer treatment; low physical activity and adiposity are risk factors for higher inflammation and shorter telomeres, placing cancer survivors at further risk of accelerated aging. Depression, which affects a subset of cancer survivors, promotes inflammation and the premature aging of immune cells (Hewitt et al., 2003; Jaremka et al., 2013). Accordingly, the combination of depression and inflammatory-related chronic diseases may be a particularly potent challenge to cell aging. The findings by Cohen and colleagues suggest that this accelerated cell aging may affect disease susceptibility among cancer survivors; shortened telomeres enhance risk of infectious (Cohen et al., in press) and age-related diseases (Epel et al., 2010). Indeed, cancer survivors experience higher rates of other comorbid illnesses, such as cardiovascular disease, than those who have not had cancer (Hewitt et al., 2003); infectious disease risk may also be higher. In sum, inflammation and accelerated cell aging represent important pre-disease mechanisms that may be improved or worsened through multiple behavioral and biomedical pathways (Kiecolt-Glaser et al., 2013). Because short telomeres predict early disease, slowing immune cell aging could have broad effects by slowing the onset of age-related diseases.

Omega-3 Supplementation and Loneliness-Related Memory Problems: Secondary Analyses Of A Randomized Controlled Trial

Objective Loneliness enhances risk for episodic memory declines over time. Omega-3 supplementation can improve cognitive function for people experiencing mild cognitive difficulties. Accordingly, we explored whether omega-3 supplementation would attenuate loneliness-related episodic memory problems. Methods Participants (n = 138) from a parent randomized controlled trial were randomized to the placebo, 1.25 grams/d of omega-3, or 2.50 grams/d of omega-3 conditions for a 4-month period. They completed a baseline loneliness questionnaire and a battery of cognitive tests both at baseline and at the end of the randomized controlled trial. Results After adjustment for baseline verbal episodic memory scores, lonelier people within the placebo condition had poorer verbal episodic memory postsupplementation, as measured by immediate (b = −0.28, t (117) = −2.62, p = .010) and long-delay (b = −0.06, t (116) = −2.07, p = .040) free recall, than their less lonely counterparts. This effect was not observed in the 1.25- and 2.50-grams/d supplementation groups (all p values > .10). The plasma omega-6:omega-3 ratio data mirrored these results. There were no loneliness-related effects of omega-3 supplementation on short-delay recall or the other cognitive tests (all p values > .32). Conclusion These results suggest that omega-3 supplementation attenuates loneliness-related verbal episodic memory declines over time and support the use of exploring novel interventions for treating episodic memory problems among lonely people. Trial Registration clinicaltrials.gov Identifier: NCT00385723.

Resilience and immune function in older adults

Normal aging is marked by dysregulated immune function or immunosenescence. However, there is considerable variation in the degree to which adults are susceptible or resilient to immune dysregulation and disease. Stress is an important factor that can further alter the aging immune system. In this chapter, we review research that shows how stress can enhance age-related immune dysregulation in a variety of clinically relevant ways. We then explore what factors promote resilience to the negative immunological consequences of stress and aging. Finally, we take a lifespan perspective to examine evidence to suggest that some of the most important factors that augment or assuage an older adults capacity for resilience to age and stress-related immune dysregulation develop long before he or she reaches older adulthood.

109. Marital status is related to Epstein-Barr virus latency in individuals undergoing cancer diagnostic procedures

Married individuals reap many health benefits, including higher 5-year relative survival rates from cancer than unmarried individuals. We investigated whether cellular immune function differed by marital status (married vs. single vs. divorced, separated, or widowed) during the stress of cancer diagnosis. Immune dysfunction was indexed by reactivation of latent Epstein-Barr virus (EBV), and was measured using EBV viral capsid antigen (VCA) IgG antibody titers. In 393 men and women awaiting or shortly following diagnosis for breast or colorectal cancer, EBV antibody titers differed significantly by marital status, p