Jean-Philippe Gouin

Childhood Adversity Heightens the Impact of Later-Life Caregiving Stress on Telomere Length and Inflammation

Objective: To address the question of whether childhood abuse and other adversities have lasting, detectable consequences for inflammation and cell aging late in life, and whether the effects are large enough to be discernible beyond that of a major chronic stressor, dementia family caregiving. Previous research on the physical health consequences of childhood abuse and other adversities has been based on data from young or middle-aged adults. Method: In this community sample of 132 healthy older adults (mean age = 69.70 years; standard deviation = 10.14), including 58 dementia family caregivers and 74 noncaregivers, blood samples were analyzed for interleukin (IL)-6, tumor necrosis factor (TNF)-&agr;, and telomere length, a measure of cell aging. Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Results: After controlling for age, caregiving status, gender, body mass index, exercise, and sleep, the presence of multiple childhood adversities was related to both heightened IL-6 (0.37 ± 0.03 log10 pg/mL versus 0.44 ± 0.03 log10 pg/mL) and shorter telomeres (6.51 ± 0.17 Kb versus 5.87 ± 0.20 Kb), compared with the absence of adversity; the telomere difference could translate into a 7- to 15-year difference in life span. Abuse was associated with heightened IL-6 and TNF-&agr; levels; for TNF-&agr;, this relationship was magnified in caregivers compared with controls. Moreover, abuse and caregiving status were associated significantly and independently with higher levels of depressive symptoms. Conclusions: Adverse childhood events are related to continued vulnerability among older adults, enhancing the impact of chronic stressors. Childhood adversities cast a very long shadow. BMI = body mass index; CES-D = Center for Epidemiological Studies Depression Scale; CRP = C-reactive protein; IL = interleukin; PBMCs = peripheral blood mononuclear cells; TNF = tumor necrosis factor.

Close relationships, inflammation, and health

Different aspects of personal relationships including social integration, social support, and social conflict have been related to inflammation. This article summarizes evidence linking the quality and quantity of relationships with gene expression, intracellular signaling mechanisms, and inflammatory biomarkers, and highlights the biological and psychological pathways through which close relationships impact inflammatory responses. Relationship conflict and lower social support can effectively modulate proinflammatory cytokine secretion both directly (via CNS/neural/endocrine/immune biobehavioral pathways), and indirectly, by promoting depression, emotional stress responses, and detrimental health behaviors. Accordingly, thorough assessments of health behaviors and attention to key methodological issues are necessary to identify the contributions of relationships to inflammation, and thus we highlight procedural issues to be considered in the design of studies. Despite some notable methodological challenges, the evidence suggests that learning more about how close relationships influence inflammation will provide important new insights into the ways that relationships impact health.

Immune Dysregulation and Chronic Stress among Older Adults: A Review

Aging is associated with a natural dysregulation in immune functioning which may be amplified when it occurs in the context of chronic stress. Family dementia caregiving provides an excellent model to study the impact of chronic stress on immune functioning among older individuals. Empirical data suggest that the stress of caregiving dysregulates multiple components of innate and adaptive immunity. Elderly caregivers have poorer responses to vaccines, impaired control of latent viruses, exaggerated production of inflammatory mediators and accelerated cellular aging, compared to noncaregiving older adults. The chronic stress-induced immune dysregulation observed among older caregivers appears to be of sufficient magnitude to impact health. Furthermore, evidence suggests that chronic stress leads to premature aging of the immune system.

The Impact of Psychological Stress on Wound Healing: Methods and Mechanisms

Converging and replicated evidence indicates that psychological stress can modulate wound-healing processes. This article reviews the methods and findings of experimental models of wound healing. Psychological stress can have a substantial and clinically relevant impact on wound repair. Physiologic stress responses can directly influence wound-healing processes. Furthermore, psychological stress can indirectly modulate the repair process by promoting the adoption of health-damaging behaviors. Translational work is needed to develop innovative treatments able to attenuate stress-induced delays in wound healing.

Chronic stress, daily stressors, and circulating inflammatory markers.

OBJECTIVES Acute laboratory stressors elicit elevations in serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP). Chronic stressors, such as family dementia caregiving, promote a state of chronic low-grade elevation in circulating inflammatory markers. The recurrent daily stressors associated with chronic stress may lead to repeated and sustained activation of the physiological stress systems. The present study evaluated the possibility that greater exposure and reactivity to daily stressors fueled increased levels of circulating inflammatory markers among family dementia caregivers, compared with noncaregiving controls. METHODS This cross-sectional study included 53 caregivers and 77 noncaregiving controls. A semistructured interview assessed the occurrence of daily stressors in the past 24 h. A blood sample provided data on two inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6). RESULTS Caregivers were more likely to experience multiple stressors in the past 24 h than noncaregiving controls. The occurrence of multiple daily stressors was associated with greater serum IL-6 and CRP levels. The greater occurrence of daily stressors in the past 24 h partially mediated the relationship between dementia caregiving and CRP levels. CONCLUSION These results suggest that the cumulative effect of daily stressors promotes elevations in inflammatory markers. Greater exposure to daily stressors may be a psychobiological mechanism leading to elevations in CRP levels among family dementia caregivers.

The Influence of Anger Expression on Wound Healing

Certain patterns of anger expression have been associated with maladaptive alterations in cortisol secretion, immune functioning, and surgical recovery. We hypothesized that outward and inward anger expression and lack of anger control would be associated with delayed wound healing. A sample of 98 community-dwelling participants received standardized blister wounds on their non-dominant forearm. After blistering, the wounds were monitored daily for 8 days to assess speed of repair. Logistic regression was used to distinguish fast and slow healers based on their anger expression pattern. Individuals exhibiting lower levels of anger control were more likely to be categorized as slow healers. The anger control variable predicted wound repair over and above differences in hostility, negative affectivity, social support, and health behaviors. Furthermore, participants with lower levels of anger control exhibited higher cortisol reactivity during the blistering procedure. This enhanced cortisol secretion was in turn related to longer time to heal. These findings suggest that the ability to regulate the expression of ones anger has a clinically relevant impact on wound healing.

Altered expression of circadian rhythm genes among individuals with a history of depression

BACKGROUND Depression has been associated with several circadian rhythm perturbations, suggesting a disruption of the circadian clock system in affective disorders. The interaction of several circadian clock genes generates these daily circadian rhythms. METHODS This cross-sectional study evaluated whether circadian gene expression differed between individuals with a history of depression and participants without a similar history. The participants were 60 healthy older adults. Half of the participants had a history of depression. Real-time quantitative polymerase chain reaction was used to measure the circadian gene Clock, BMAL1, Period1, and Period2 messenger RNA levels in peripheral blood leukocytes. RESULTS Individuals with a history of depression had higher Clock, Period1, and Bmal1 mRNA levels, compared to non-depressed participants. LIMITATIONS Although circadian gene expression fluctuates throughout the day, clock gene mRNA levels were evaluated only in the morning. CONCLUSIONS These results suggest that disruptions of the molecular mechanisms underlying the circadian clock system may be associated with depression.

Neuroimaging findings in primary insomnia

State-of-the-art neuroimaging techniques have accelerated progress in the study and understanding of sleep in humans. Neuroimaging studies in primary insomnia remain relatively few, considering the important prevalence of this disorder in the general population. This review examines the contribution of functional and structural neuroimaging to our current understanding of primary insomnia. Functional studies during sleep provided support for the hyperarousal theory of insomnia. Functional neuroimaging also revealed abnormalities in cognitive and emotional processing in primary insomnia. Results from structural studies suggest neuroanatomical alterations in primary insomnia, mostly in the hippocampus, anterior cingulate cortex and orbitofrontal cortex. However, these results are not well replicated across studies. A few magnetic resonance spectroscopy studies revealed abnormalities in neurotransmitter concentrations and bioenergetics in primary insomnia. The inconsistencies among neuroimaging findings on insomnia are likely due to clinical heterogeneity, differences in imaging and overall diversity of techniques and designs employed. Larger samples, replication, as well as innovative methodologies are necessary for the progression of this perplexing, yet promising area of research.

Sleep Spindles Predict Stress-Related Increases in Sleep Disturbances

Background and Aim: Predisposing factors place certain individuals at higher risk for insomnia, especially in the presence of precipitating conditions such as stressful life events. Sleep spindles have been shown to play an important role in the preservation of sleep continuity. Lower spindle density might thus constitute an objective predisposing factor for sleep reactivity to stress. The aim of this study was therefore to evaluate the relationship between baseline sleep spindle density and the prospective change in insomnia symptoms in response to a standardized academic stressor. Methods: Twelve healthy students had a polysomnography recording during a period of lower stress at the beginning of the academic semester, along with an assessment of insomnia complaints using the insomnia severity index (ISI). They completed a second ISI assessment at the end of the semester, a period coinciding with the week prior to final examinations and thus higher stress. Spindle density, amplitude, duration, and frequency, as well as sigma power were computed from C4–O2 electroencephalography derivation during stages N2–N3 of non-rapid-eye-movement (NREM) sleep, across the whole night and for each NREM sleep period. To test for the relationship between spindle density and changes in insomnia symptoms in response to academic stress, spindle measurements at baseline were correlated with changes in ISI across the academic semester. Results: Spindle density (as well as spindle amplitude and sigma power), particularly during the first NREM sleep period, negatively correlated with changes in ISI (p < 0.05). Conclusion: Lower spindle activity, especially at the beginning of the night, prospectively predicted larger increases in insomnia symptoms in response to stress. This result indicates that individual differences in sleep spindle activity contribute to the differential vulnerability to sleep disturbances in the face of precipitating factors.

Poor sleep as a pathophysiological pathway underlying the association between stressful experiences and the diurnal cortisol profile among children and adolescents

Recent evidence suggests that poor sleep is a potential pathway underlying the association between stressful experiences and the diurnal cortisol profile. However, existing findings are largely limited to adults. The present study examines whether poor sleep (duration, quality) mediates the relation between stressful experiences and the diurnal cortisol profile in children and adolescents. Children and adolescents (N = 220, M(age) = 12.62) provided six saliva samples over two days to derive cortisol indices (bedtime, AUCAG, AUCTG, slope(MAX)). Perceived stress, stressful life events, self-reported sleep duration, and sleep quality were measured. Using bootstrapping analyses, sleep quality mediated the relation between perceived stress and AUCTG (R(2) = 0.10, F(7, 212) = 3.55, p = .001; 95% BCI[0.09, 1.15]), as well as the relation between stressful life events and AUCTG (R(2) = 0.11, F(7, 212) = 3.69, p = .001; 95% BCI[0.40, 3.82]). These mediation models remained significant after adjusting for sleep duration, suggesting that poor sleep quality underlies the association between stressful experiences and the diurnal cortisol profile in children and adolescents. Longitudinal data combined with objectively-measured sleep is essential to further disentangle the complex association between sleep and stress.