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)-α, 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-α levels; for TNF-α, 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.

Caregivers of Alzheimer’s disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-α and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.

This article reviews and develops some theories about the neurobiological basis of creative innovation (CI). CI is defined as the ability to understand and express novel orderly relationships. A high level of general intelligence, domain-specific knowledge and special skills are necessary components of creativity. Specialized knowledge is stored in specific portions of the temporal and parietal lobes. Some anatomic studies suggest that talented people might have alterations of specific regions of the posterior neocortical architecture, but further systematic studies are needed. Intelligence, knowledge and special skills, however, are not sufficient for CI. Developing alternative solutions or divergent thinking has been posited to be a critical element of CI, and clinical as well as functional imaging studies suggest that the frontal lobes are important for these activities. The frontal lobes have strong connections with the polymodal and supramodal regions of the temporal and parietal lobes where concepts...

Stress-induced activation of the locus ceruleus-norepinephrine (LC-NE) system produces significant cognitive and behavioral effects, including enhanced arousal and attention. Improvements in discrimination task performance and memory have been attributed to this stress response. In contrast, for other cognitive functions that require cognitive flexibility, increased activity of the LC-NE system may produce deleterious effects. The aim of the present study was to determine the effect of pharmacological modulation of the LC-NE system on stress-induced impairments in cognitive flexibility performance in healthy individuals. Cognitive performance, plus psychological and physiological parameters for 16 adults without any history of anxiety disorders, was assessed during four test sessions: stress and no-stress, with each condition tested after administration of propranolol and placebo. The Trier Social Stress Test, a public-speaking and mental arithmetic stressor, was presented to participants for the stress sessions, whereas a similar, but nonstressful, control task (reading, counting) was utilized for the no-stress sessions. Tests of cognitive flexibility included lexical-semantic and associative problem-solving tasks (anagrams, Compound Remote Associates Test). Visuo-spatial memory and motor processing speed tests served as control tasks. Results indicate that (1) stress impaired performance on cognitive flexibility tasks, but not control tasks; (2) compared to placebo, cognitive flexibility improved during stress with propranolol. Therefore, psychological stress, such as public speaking, negatively impacts performance on tasks requiring cognitive flexibility in normal individuals, and this effect is reversed by beta-adrenergic antagonism. This may provide support for the hypothesis that stress-related impairments in cognitive flexibility are related to the noradrenergic system.

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. 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). 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. 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.