Vulnerability, distress, and immune response to vaccination in older adults.

Psychological distress and biobehavioral vulnerability (e.g., arising from being older or sedentary) have independently predicted immune responses to influenza vaccination in older adults. Recent research examining basal inflammatory markers suggests that, rather than having additive effects, distress and vulnerability interact with each other. The present study tested the interactions between distress and age, sex, education, BMI, sleep quality, and physical activity over up to 8 years in older adults (N=134; M age=74 years) who received annual influenza vaccinations. Measured vaccination responses were changes from baseline in antibody to the three vaccine components, interleukin (IL)-6, and ß2-microglobulin. As predicted, the most robust effects were interactions between distress and vulnerability. BMI interacted with stable individual differences in distress to predict antibody response (t(132)=3.09, p<0.003), such that only the combination of low BMI and low distress was associated with a more robust antibody response. Likewise, changes in physical activity over time interacted with changes in distress (t(156)=2.96, p<0.004), such that only the combination of increased physical activity and decreased distress was associated with a more robust antibody response. Finally, there was a smaller tendency for age to interact with stable individual differences in distress (t(130)=2.46, p<0.015), such that distress was more strongly associated with post-vaccination IL-6 at older ages. The synergistic effects of distress and other forms of vulnerability are an important direction for future research and a target for interventions to improve immunological health in older adults.

Exposure and reactivity to repetitive thought in the neuroticism-distress relationship.

INTRODUCTION: Distress has been assumed to result from exposure to repetitive thought (RT). However, if RT is viewed as internally generated stressors, both exposure and affective reactivity to RT could play roles in generating distress. METHODS: Three studies (young adults, N=99; midlife women, N=111; older adults, N=159) assessed exposure and reactivity to daily RT and tested whether neuroticism was related to individual differences in both exposure and affective reactivity. RESULTS: Across all 3 studies, reactivity effects on depressive symptoms exceeded those of exposure to RT, and neuroticism was associated with more exposure and greater affective reactivity. Furthermore, RT exposure and reactivity accounted for most when not all of the relationship between neuroticism and depressive symptoms. DISCUSSION AND CONCLUSIONS: Further consideration of both exposure and affective reactivity to RT can not only increase the explanatory power of this construct but also suggest effective targets for intervention.

Effects of norketamine enantiomers in rodent models of persistent pain.

NMDA-receptor antagonists are potential drugs for chronic pain treatment, in particular for neuropathic pain involving central sensitization processes. Clinical use of available NMDA antagonists, such as ketamine, is limited for this indication due to its side effects (psychotomimetic, sedative, motor). There is a need for novel NMDA-receptor antagonist(s) with better analgesia/toxicity profile(s). One such potential candidate is norketamine, a primary metabolite of ketamine. S(+) and R(-)norketamine were characterized utilizing rodent models of persistent pain: the chronic constriction nerve injury model of peripheral neuropathy (CCI) and the formalin-injection model of tonic inflammatory pain (formalin test). Side effects (motor coordination, stereotypic behaviors, locomotor activity) were also assessed. (+/-)Ketamine served as a reference NMDA-receptor antagonist in some studies. Norketamine alleviated, in a dose-dependent fashion, mechanical and thermal hyperalgesia (CCI), and blocked formalin-induced flinches (2nd phase). It had less effect on tactile allodynia (CCI). Efficacy was demonstrated after parenteral and oral administration. The antinociceptive properties resided primarily in the S(+) enantiomer. Antinociception was not accompanied by significant side effects. The present findings suggest that norketamine, in particular the S(+) enantiomer, might be a useful NMDA-receptor antagonist for treatment of chronic pain involving central sensitization.

The Relationship Between Life Purpose With Depression and Disability in Acute Low Back Pain Patients.

BACKGROUND: Life purpose in acute low back pain patients is not well described in published literature. METHODS/PURPOSE: We used linear regression models to describe the relationship of life purpose with perceived functional disability and depression in persons with acute low back pain (N = 42) participating in a randomized clinical trial to prevent transition to chronic low back pain. RESULTS: In our predominantly female sample (81.8%) with a mean age of 53 years (SD = 11.6 years), 52% worked full-time. Adjusting for age, gender, and working status, life purpose was a significant correlate of depression (p = .007). For every 10-unit increase in life purpose score, the estimated depression score decreased by almost 2.5 points. A significant relationship between life purpose and perceived functional disability was not identified. CONCLUSION: Life purpose likely is a modifiable risk factor for depression in acute low back pain patients.

Briefly Assessing Repetitive Thought Dimensions: Valence, Purpose, and Total.

Discrete forms of repetitive thought (RT), such as worry and reflection, can be characterized along basic dimensions of valence (positive vs. negative) and purpose (searching vs. solving). In addition, people can be characterized as high or low in their tendency to engage in RT. This dimensional model has been demanding to assess, and a smaller number of items that could stand in for a large battery would make measurement more accessible. Using four samples (N = 1,588), eight items that assess RT valence, purpose, and total in a circumplex model were identified. Across these and other samples, the dimensions were adequately reliable and valid with regard to assessment via large RT battery, other measures of RT, and depressive symptoms. The accessibility of dimensional assessment of RT using this smaller number of items should facilitate work on questions about the qualities of RT that predict mental and physical health.

Episodic repetitive thought: dimensions, correlates, and consequences.

Repetitive thought (RT) - attentive, prolonged, or frequent thought about oneself and one's world - plays an important role in many models of psychological and physical ill health (e.g., rumination and worry), as well as models of recovery and well-being (e.g., processing and reminiscing). In these models, repetitive thought is typically treated as stable or trait-like. In contrast, episodic RT reflects what people have "on their minds" at a particular point in time. In four studies, young women (N=94), college students (N=166), first-year law students (N=73), and older adults (N=174) described their episodic RT, which was then rated for qualities including valence, purpose, and theme. Episodic RT valence was associated with mood and depressive symptoms both between (Studies 1-4) and within people (Studies 3-4), and it mediated the effects of dispositional coping through emotional approach (Study 1). The effect of episodic RT valence in turn was moderated by other properties of episodic RT, including purpose, "trait" valence, and theme (Studies 1-4). The study of episodic RT complements that of trait RT and allows for observations of how RT and psychological adjustment change in concert and in context, as well as examining how the RT qualities that are not reflected in trait measures affect adjustment.

Goal conflict, distress, and pain in women with fibromyalgia: a daily diary study.

OBJECTIVES: A chronic illness such as fibromyalgia can interfere with daily activities and goals by limiting available resources, including time and energy. This leads to competition between goals, known as goal conflict. The purpose of this study was to determine if goal conflict increases symptoms in women with fibromyalgia and whether symptoms lead to perceptions of goal conflict. METHODS: Women with fibromyalgia (N=27) recorded their pain, emotional distress, and fatigue each morning and evening for five consecutive days. Each evening, they listed that day's goals, rating goals on their level of conflict. Goal conflict was also rated by independent raters, and a difference score reflected goal conflict discrepancy. RESULTS: On days with higher goal conflict, pain increased more from morning to evening (γ=1.71, 95% confidence interval=0.32-3.09, P<.05). On days with higher morning emotional distress, goal conflict was overestimated (γ=0.075, 95% confidence interval=0.035-0.116, P<.05). Women who had a higher symptom burden also typically overestimated their goal conflict relative to those with fewer symptoms (P<.05 for all). CONCLUSIONS: Goal pursuit may deplete psychological and physical resources in this vulnerable population, resulting in higher pain. Conversely, emotional distress may affect perception of goal conflict, resulting in less ambitious goal pursuit. Understanding the dynamic relationship between goal conflict and fibromyalgia symptoms may lead to more effective management of limited resources and pursuit of daily goals with fibromyalgia.

The analgesic and toxic effects of nornicotine enantiomers alone and in interaction with morphine in rodent models of acute and persistent pain.

Neuronal nicotinic acetylcholinic receptors (nAChR) are promising targets for the development of novel analgesics. Nicotine and other nAChR-agonists produce profound analgesia in rodent models of acute and persistent pain. However, significant side-effects are of concern. Nornicotine (N-desmethyl-nicotine) appears to activate different nAChR subtypes, has a better pharmacokinetic profile, and produces less toxicity than nicotine. Little is known about its analgesic properties. In the present study, the S(-)- and R(+)-enantiomers of nornicotine were characterized with regard to analgesia and side-effects profile. Efficacy was demonstrated in rat models of pain where central sensitization is involved: i.e. the chronic constriction nerve injury model of peripheral neuropathy and the formalin model of tonic inflammatory pain. The desirable (analgesic) properties resided predominantly in the S(-)- rather than the R(+)-enantiomer. In contrast, undesirable effects (motor in-coordination, reduced locomotor activity, ataxia) were more pronounced with the R(+)-enantiomer. This is an interesting finding, which may suggest separation of toxicity from analgesia by utilization of S(-)-enantiomer of nornicotine. Maximum analgesic effectiveness without significant side-effects was achieved when S(-)-nornicotine (sub-analgesic dose) was combined with a low-dose of the micro-opioid, morphine. These preclinical data suggest that S(-)-nornicotine may be of value, either alone or in combination with an opioid, for treatment of a broad-spectrum of pain (i.e. nociceptive, neuropathic, and mixed pain).