Mats Lekander

Evaluating the effectiveness of exposure and acceptance strategies to improve functioning and quality of life in longstanding pediatric pain - A randomized controlled trial

ABSTRACT Although several studies have illustrated the effectiveness of cognitive behavior therapy (CBT) on adult pain patients, there are few randomized controlled trials on children and adolescents. There is particularly a need for studies on pediatric patients who are severely disabled by longstanding pain syndromes. Acceptance and Commitment Therapy, as an extension of traditional CBT, focuses on improving functioning and quality of life by increasing the patient’s ability to act effectively in concordance with personal values also in the presence of pain and distress. Following a pilot study, we sought to evaluate the effectiveness of an ACT‐oriented intervention based on exposure and acceptance strategies and to compare this with a multidisciplinary treatment approach including amitriptyline (n = 32). The ACT condition underwent a relatively brief treatment protocol of approximately 10 weekly sessions. Assessments were made before and immediately after treatment, as well as at 3.5 and 6.5 months follow‐up. Prolonged treatment in the MDT group complicated comparisons between groups at follow‐up assessments. Results showed substantial and sustained improvements for the ACT group. When follow‐up assessments were included, ACT performed significantly better than MDT on perceived functional ability in relation to pain, pain intensity and to pain‐related discomfort (intent‐to‐treat analyses). At post‐treatment, significant differences in favor of the ACT condition were also seen in fear of re/injury or kinesiophobia, pain interference and in quality of life. Thus, results from the present study support previous findings and suggest the effectiveness of this ACT‐oriented intervention for pediatric longstanding pain syndromes.

Less effective executive functioning after one night's sleep deprivation

The prefrontal cortex (PFC) is affected negatively by sleep deprivation (SD) and executive functioning is largely dependent on activity in the PFC. Earlier studies have focused on subsystems of executive functioning, and tests of executive functioning have shown both low reliability and low validity. In the present study, 11 healthy volunteers were sleep deprived and compared with 11 healthy controls in a study on effects of one nights SD on integrative executive functioning. Following SD, the performance of subjects on an ecologically valid test, the modified Six Elements Test, was significantly impaired. There were no group differences on psychomotor vigilance, verbal or visuo‐spatial working memory. This extends previous knowledge of performance effects of SD, and may be of special importance for individuals with cognitive work tasks.

Self-rated health and vital exhaustion, but not depression, is related to inflammation in women with coronary heart disease.

Poor subjective well-being has been associated with increased coronary heart disease (CHD) morbidity and mortality in population-based studies and with adverse outcomes in existing CHD. Little is known about the mechanisms responsible for this association, but immune activity appears to be a potential pathway. Despite the growing evidence linking immune activity to subjective feelings, very few studies have examined patients with CHD, and the results are conflicting. We examined consecutive women patients hospitalized for acute myocardial infarction, and/or underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. We assessed depression, vital exhaustion, and self-rated health by questionnaires. Circulating levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) concentrations were determined. After controlling for potential confounding factors there was a significant positive correlation between IL-6 levels and vital exhaustion and poor self-rated health. The association between hsCRP and vital exhaustion and self-rated health was borderline significant. In contrast, the correlations between psychological factors and IL-1ra levels were weak and non-significant, as were the correlations between inflammatory markers and depression. Similar relationships between the inflammatory markers and the measures of psychological well-being were obtained when the latter ones were categorized into tertiles. In conclusion, inflammatory activity, assessed by IL-6 and hsCRP levels, was associated with vital exhaustion and self-rated health in CHD women. These findings may provide further evidence for a possible psychoneuroimmune link between subjective well-being and CHD. Our observations also raise the possibility that a cytokine-induced sickness response in CHD may be better represented by constructs of vital exhaustion and self-rated health than of depression.

Self-rated health is related to levels of circulating cytokines.

Objective: Self-rated health is a powerful and independent predictor of long-term health, but its biological basis is unknown. Because factors associated with poor self-rated health (eg, pain, daily discomforts, and low energy and fitness) resemble symptoms of a generalized cytokine-induced sickness response, we examined the relationship between circulating cytokines and self-rated health. Methods: In 265 consecutive primary health care patients (174 women and 91 men), we examined self-rated and physician-rated health, circulating levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor (TNF)-&agr; as determined from plasma samples using high-sensitivity enzyme-linked immunoassay. Results: Self-rated health correlated with levels of IL-1β (r = 0.27; p < .001), IL-1ra (r = 0.19; p < .05) and TNF-&agr; (r = 0.46; p < .001) in women but not in men. Thus, poorer subjective health was associated with higher levels of inflammatory cytokines. Even when controlling for age, education, physical health, and diagnoses in multiple regression analyses, self-rated health was an independent and more robust predictor of cytokine levels than physician-rated health. Conclusions: The present findings suggest that an individuals health perception may be coupled to circulating cytokines. Because epidemiological research established that self-rated health predicts morbidity and mortality, the biological correlates and mechanisms of self-rated health need to be understood.

Sleepiness and performance in response to repeated sleep restriction and subsequent recovery during semi-laboratory conditions.

There is an ongoing debate of how best to measure the effects of sleep loss in a reliable and feasible way, partly because well controlled laboratory studies and field studies have come to different conclusions. The aims of the present study were to investigate both sleepiness and performance in response to long‐term sleep restriction and recovery in a semi‐laboratory environment, investigate order effects (i.e., whether levels return to baseline) in a study with seven days of recovery, and characterize individual differences in tolerance to restricted sleep. Nine healthy men (age 23–28 yrs) participated in the protocol, which included one habituation day (sleep 23:00–07:00 h), two baseline days (23:00–07:00 h), five days with restricted sleep (03:00–07:00 h), and seven recovery days (23:00–07:00 h). Participants went outdoors at least twice each day. Reaction‐time tests were performed at 08:00, 14:00, and 20:00 h each day in the laboratory. Sleepiness was self‐rated by the Karolinska Sleepiness Scale (KSS) after each test. The mixed‐effect regression models showed that each day of restricted sleep resulted in an increase of sleepiness by 0.64±.05 KSS units (a nine‐step scale, p<.001), increase of median reaction times of 6.6±1.6 ms (p=.003), and increase of lapses/test of 0.69±.16 ms (p<.001). Seven days of recovery allowed participants to return to the baseline for sleepiness and median reaction time, but not for lapses. The individual differences were larger for performance measures than for sleepiness; the between‐subject standard deviation for the random intercept was in the magnitude of the effects of 1.1 days of restricted sleep for sleepiness, 6.6 days of restricted sleep for median reaction time, and 3.2 days for lapses. In conclusion, the present study shows that sleepiness is closely related to sleep pressure, while performance measures, to a larger extent, appear determined by specific individual traits. Moreover, it is suggested to measure sleepiness in a standardized situation so as to minimize the influences of contextual factors.

The Scent of Disease Human Body Odor Contains an Early Chemosensory Cue of Sickness

Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals’ level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a “behavioral immune response” that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

Changes in immune regulation in response to examination stress in atopic and healthy individuals

Background Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown.

A putative role for cytokines in the impaired appetite in depression

Impaired appetite and weight changes are commonly seen in patients with depression, but the pathophysiology behind this imbalance between energy intake and energy expenditure remains largely unknown. The aim of this paper is to review the literature regarding a possible role for cytokines in the regulation of appetite and body weight, with special emphasis on depression. There now exists a substantial amount of evidence that depressed patients show signs of immune activation including increased levels of proinflammatory cytokines. Cytokines, which by themselves have anorectic properties, stimulate the release of the cytokine-like anorexogenic peptide leptin. In addition to their anorectic properties, both proinflammatory cytokines and leptin interact with the hypothalamic-pituitary-adrenal (HPA) axis, the sympathetic nervous system (SNS) and the immune system. In turn, these systems regulate energy balance as well as they are dysfunctional in depression. Furthermore, both proinflammatory cytokines and leptin can induce anhedonia, one of the cardinal symptoms of depression. In view of the different effects on appetite and/or body weight observed in melancholic versus atypical depression, we suggest that cytokines are differentially altered in these subtypes of depression, and that this may explain some of the inconsistency in the reported findings of cytokine as well as leptin levels in depressed patients. Finally, we propose that the immune system uses the interoceptive pathway projecting to the insular cortex, a brain region where cytokine-induced changes in appetite could be partly mediated, and that this pathway is activated in depression.

Inflammatory markers and heart rate variability in women with coronary heart disease.

Purpose.  Both heart rate variability (HRV) and inflammatory markers are carrying prognostic information in coronary heart disease (CHD), however, we know of no studies examining their relation in CHD. The aim of this study, therefore, was to assess the association between HRV and inflammatory activity, as reflected by the levels of interleukin‐6 (IL‐6), IL‐1 receptor antagonist (IL‐1ra) and C‐reactive protein (CRP).

Inflammatory cytokines, behaviour and age as determinants of self-rated health in women

Self-rated health is a powerful and independent predictor of long-term health, but its biological basis is unknown. We have shown previously that self-rated health is associated with increased levels of circulating cytokines in women. The main aim of the present study was to increase the understanding of the association between markers of wellbeing, such as self-rated health, and cytokines and to investigate the impact of age on these associations. In 174 female consecutive primary health care patients divided into three age groups, we examined subjective ratings of health and aspects of wellbeing and circulating levels of IL (interleukin)-1beta, IL-1ra (IL-1 receptor antagonist), IL-6 and TNF-alpha (tumour necrosis factor-alpha). Poor self-rated health was significantly associated with higher levels of TNF-alpha in all of the age groups. For IL-1beta and IL-1ra, the correlations with self-rated health were significant only in the oldest age group. Lower ratings of other measurements of health and wellbeing were related to higher levels of cytokines, most pronounced for TNF-alpha and IL-1beta, and in the middle and olderst age groups. More symptoms resembling a sickness response induced by inflammation were implicated to be associated with lower self-rated health. The strength of the association between inflammatory cytokines and poor health perception increased with advanced age, indicating an increased vulnerability for inflammatory activity during aging. It is suggested that higher levels of TNF-alpha are connected to a sickness response that, in turn, is connected to self-rated health. The results provide a possible psychobiological basis to understand better diffuse subjective symptoms and poor subjective health in women.