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Background: The Health Anxiety Inventory (HAI), the Illness Attitude Scales (IAS), and the Whiteley Index (WI) are three of the most widely used health anxiety measures, but their psychometric properties have not been investigated when administered via the Internet., Methods: We investigated the three instruments' test-retest reliability, internal consistency, convergent, and discriminant validity and sensitivity to change using one sample (n=111) of participants with severe health anxiety and one sample of healthy controls (n=92)., Results: The HAI, IAS, and WI showed high test-retest reliability (rs≥.80), good convergent, and discriminant validity and were sensitive to detect change. The HAI and IAS (αs≥.85), but not the WI (αs≤.60) demonstrated high internal consistency., Conclusions: The HAI, IAS, and WI have good psychometric properties, except for the low internal consistency of WI, when used as Internet-administered measures of health anxiety. Using these measures over the Internet offers highly important advantages such as increased ease of administration, reduced attrition, and cost-efficient treatment evaluation., (Copyright © 2015. Published by Elsevier Ltd.)

Severe health anxiety can be effectively treated with exposure-based Internet-delivered cognitive behavior therapy (ICBT), but information about which factors that predict outcome is scarce. Using data from a recently conducted RCT comparing ICBT (n = 79) with Internet-delivered behavioral stress management (IBSM) (n = 79) the presented study investigated predictors of treatment outcome. Analyses were conducted using a two-step linear regression approach and the dependent variable was operationalized both as end state health anxiety at post-treatment and as baseline-to post-treatment improvement. A hypothesis driven approach was used where predictors expected to influence outcome were based on a previous predictor study by our research group. As hypothesized, the results showed that baseline health anxiety and treatment adherence predicted both end state health anxiety and improvement. In addition, anxiety sensitivity, treatment credibility, and working alliance were significant predictors of health anxiety improvement. Demographic variables, i.e. age, gender, marital status, computer skills, educational level, and having children, had no significant predictive value. We conclude that it is possible to predict a substantial proportion of the outcome variance in ICBT and IBSM for severe health anxiety. The findings of the present study can be of high clinical value as they provide information about factors of importance for outcome in the treatment of severe health anxiety., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Unlabelled: Personality traits have traditionally been viewed as stable, but recent studies suggest that they could be affected through psychological treatment. Internet-based cognitive behavior therapy (ICBT) for severe health anxiety (DSM-IV hypochondriasis) has been shown to be effective in reducing health anxiety, but its effect on measures of personality traits has not been investigated. The main aim of this study was to investigate the impact of ICBT on personality traits in the three broad dimensions--neuroticism, extraversion and aggression. We hypothesized that participants in ICBT would reduce their level of neuroticism compared to controls that did not receive the active treatment. No specific predictions were made regarding extraversion and aggression. Data from a randomized controlled trial were used in which participants were allocated to 12 weeks of ICBT (n = 40) or to a basic attention control condition (n = 41). Personality traits were assessed with the Swedish Universities Scales of Personality and the primary outcome of health anxiety was the Health Anxiety Inventory. There was a significant interaction effect of group and time on neuroticism-related scales, indicating larger pre- to post-treatment reductions in the Internet-based CBT group compared to the control condition. Analyses at 6-month follow-up showed that changes were stable. Traits relating to extraversion and aggression were largely unchanged. This study is the first to demonstrate that a brief ICBT intervention for severe health anxiety causes long-term changes in measures of personality traits related to neuroticism. The treatment thus has a broader impact than just reducing health anxiety., Trial Registration: Clinicaltrials.gov (ID NCT00828152).

Background: Exposure-based cognitive-behavioural therapy (CBT) delivered via the internet has been shown to be effective for severe health anxiety (hypochondriasis) but has not been compared with an active, effective and credible psychological treatment, such as behavioural stress management (BSM)., Aims: To investigate two internet-delivered treatments - exposure-based CBT v. BSM - for severe health anxiety in a randomised controlled trial (trial registration: NCT01673035)., Method: Participants (n = 158) with a principal diagnosis of severe health anxiety were allocated to 12 weeks of exposure-based CBT (n = 79) or BSM (n = 79) delivered via the internet. The Health Anxiety Inventory (HAI) was the primary outcome., Results: Internet-delivered exposure-based CBT led to a significantly greater improvement on the HAI compared with BSM. However, both treatment groups made large improvements on the HAI (pre-to-post-treatment Cohen's d: exposure-based CBT, 1.78; BSM, 1.22)., Conclusions: Exposure-based CBT delivered via the internet is an efficacious treatment for severe health anxiety., (Royal College of Psychiatrists.)

Social anxiety disorder (SAD) is common, debilitating and associated with high societal costs. The disorder can be effectively treated with Internet-based cognitive behavior therapy (ICBT), but no previous study has investigated the long-term clinical or health economic effects of ICBT for SAD in comparison to an evidence-based control treatment. The aim of the study was to investigate the clinical effectiveness and cost-effectiveness of ICBT compared to cognitive behavioral group therapy (CBGT) four years post-treatment. We conducted a 4-year follow-up study of participants who had received ICBT or CBGT for SAD within the context of a randomized controlled non-inferiority trial. The cost-effectiveness analyses were conducted taking a societal perspective. Participants in both treatment groups made large improvements from baseline to 4-year follow-up on the primary outcome measure (d = 1.34-1.48) and the 95% CI of the mean difference on the primary outcome was well within the non-inferiority margin. ICBT and CBGT were similarly cost-effective and both groups reduced their indirect costs. We conclude that ICBT for SAD yields large sustainable effects and is at least as long-term effective as CBGT. Intervention costs of both treatments are offset by net societal cost reductions in a short time., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Fatigue is related to a number of serious diseases, as well as to general well-being. It is also a major cause of sickness absence and use of health facilities. Still, the determinants of variations in fatigue are little investigated. The purpose of present study was to investigate the relationships between the daily variations of fatigue with sleep during the previous night, stress or disease symptoms during the same day - across 42 consecutive days of normal life., Methods: 50 individuals participated and gave diary reports and used an actigraph across the 42days. The data was analyzed using a multilevel approach with mixed model regression., Results: The analyses showed that the day-to-day variation in fatigue was related to (poor) sleep quality (p<.001) and (reduced) sleep duration (p<.01) the previous night, as well as to higher stress (p<.05), and to the occurrence of a cold or fever (p<.001) during the same day as the fatigue rating. Fatigue was also strongly related to poorer subjective health (p<.001) and sleepiness (p<.001) during the same day., Conclusion: The results indicate that prior sleep (and sleepiness) as well as stress and illness are consistently connected to how fatigue is experienced during normal living conditions., (Copyright © 2014 Elsevier Inc. All rights reserved.)

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.

Objective: A sudden gain is defined as a large and stable individual improvement occurring between two consecutive treatment sessions. Sudden gains have been shown to predict better long-term improvement in several treatment studies, including cognitive behavioural therapy for depression and anxiety disorders, but have not been studied in the treatment of health anxiety or any form of internet-based cognitive behavioural therapy. The aim of this study was to investigate the role of sudden gains in internet-based cognitive behavioural therapy for severe health anxiety., Method: We examined the occurrence and significance of sudden gains in measures of health anxiety in 81 participants receiving internet-based cognitive behavioural therapy. We compared patients with sudden gains, patients without sudden gains, and patients with gradual gains., Results: Thirteen participants (16%) experienced one sudden gain in health anxiety with individual sudden gains distributed across the treatment. As expected, patients with a sudden gain showed larger improvements than patients without a sudden gain at post-treatment (d = 1.04) and at one-year follow-up (d = 0.91) on measures of health anxiety., Conclusions: Consistent with previous studies, sudden gains in internet-based cognitive behavioural therapy are associated with significantly larger and stable treatment effects up to one-year follow-up., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Despite the common notion that stress impairs sleep there is little published data showing that sleep (polysomnography (PSG)) is impaired across several sleep episodes in individuals who complain of daily stress during the same period. The present paper aimed at investigating such a connection. 33 subjects had 3 sleeps recorded with PSG at home across 6 weeks and kept a sleep/wake diary each day, including 3-hourly ratings of stress (scale 1-9). The stress ratings and the conventional PSG parameters were averaged across time. A stepwise multiple regression analysis showed that the best predictors of stress were Stage 1 sleep (beta = 0.49), latency to Stage 1 sleep (0.47) (adjusted for anxiety and age). Other sleep continuity variables had significant correlations with stress (reversed) but did not enter the multiple regression analysis. The correlation between stress before the start of the study and PSG data was not significant. It was concluded that moderately increased stress over a longer period of time is related to moderate signs of disturbed sleep during that period. This may be of importance when considering stress as a work environment problem.

Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion., Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00-07.00 h) followed by 5 days with restricted sleep (03.00-07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-α), interleukin (IL) -1β, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed., Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-α and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day., Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

Sleep and subjective health are both prospectively related to objective indices of health and health care use. Here, we tested whether five days with restricted sleep and subsequent recovery days affect subjective health and is related to increased levels of circulating IL-6 and TNF-α and fatigue. Nine healthy men (23-28 ears) went through a 6-week sleep protocol with subjects as their own controls in a repeated measures design with a total of 11 nights in a sleep laboratory. The experimental part of the protocol included three baseline days (sleep 23-07 h), five days with sleep restriction (03-07 h) and three recovery days (23-07 h) in the sleep laboratory. Subjective health and fatigue was recorded daily. Eight blood samples were drawn each day (every third hour) on 8 days of the protocol and analyzed with respect to IL-6 and TNF-α. Subjective health deteriorated gradually during restricted sleep (p=.002) and returned to baseline levels after three days of recovery. IL-6 and TNF-α did not change significantly. Fatigue increased gradually during sleep restriction (p=.001), which significantly contributed to the association between restricted sleep and subjective health. The study is the first to show that subjective health is directly responsive to changes in sleep length and related to increased fatigue. Thus, subjective health is differently appraised after manipulation of one of its presumed determinants. Larger experimental studies would be beneficial to further distinguish causation from association regarding the underpinnings of subjective health., (Copyright © 2013. Published by Elsevier Inc.)

Background: Atopic asthma is characterized by Th2 cytokine-driven inflammation of the airway mucosa, which is signaled by the fraction of exhaled nitric oxide (FENO)., Objective: We tested whether an FENO-guided anti-inflammatory treatment algorithm could improve asthma-related quality of life and asthma symptom control, and reduce exacerbations in atopic asthmatics within primary care., Methods: Altogether, 187 patients with asthma and who were nonsmokers (age range, 18-64 years) with perennial allergy and who were on regular inhaled corticosteroid treatment were recruited at 17 primary health care centers, randomly assigned to 2 groups and followed up for 1 year. For the controls (n = 88), FENO measurement was blinded to both operator and patient, and anti-inflammatory treatment was adjusted according to usual care. In the active group (n = 93), treatment was adjusted according to FENO. Questionnaires on asthma-related quality of life (Mini Asthma Quality of Life Questionnaire) and asthma control (Asthma Control Questionnaire) were completed, and asthma events were noted., Results: The Asthma Control Questionnaire score change over 1 year improved significantly more in the FENO-guided group (-0.17 [interquartile range {IQR}, -0.67 to 0.17] vs 0 [-0.33 to 0.50]; P = .045), whereas the Mini Asthma Quality of Life Questionnaire score did not (0.23 [IQR, 0.07-0.73] vs 0.07 [IQR, -0.20 to 0.80]; P = .197). The change in Asthma Control Questionnaire was clinically important in subpopulations with poor control at baseline (P = .03). Furthermore, the exacerbation rate (exacerbations/patient/y) was reduced by almost 50% in the FENO-guided group (0.22 [CI, 0.14-0.34] vs 0.41 [CI, 0.29-0.58]; P = .024). Mean overall inhaled corticosteroid use was similar in both groups (P = .95)., Conclusion: Use of FENO to guide anti-inflammatory treatment within primary care significantly reduced the exacerbation rate and improved asthma symptom control without increasing overall inhaled corticosteroid use., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

According to the cognitive behavioral model of severe health anxiety (hypochondriasis) four central maintaining mechanisms are how the individual perceives the risk of disease and how negative its consequences would be, attention to bodily sensations, and intolerance of uncertainty. The aim of the present study was to investigate the mediating role of these putative mechanisms in Internet-delivered CBT for severe health anxiety. We analyzed data from an RCT where participants were randomized to Internet-delivered CBT (n=40) or to a control condition (n=41). Mediators and outcome, i.e. health anxiety, were assessed weekly throughout the treatment, enabling fulfillment of the criterion of temporal precedence of changes occurring in the mediator in relation to the outcome to be met. The results showed that reduced perceived risk of disease, less attention to bodily symptoms, and reduced intolerance of uncertainty significantly mediated improvement in health anxiety. The study supports the validity of the cognitive behavioral model of health anxiety. The findings have theoretical and clinical implications as they indicate processes that may be causally related to the improvements observed after CBT for health anxiety.

Internet-based cognitive behavior therapy (CBT) for severe health anxiety can be effective, but not all patients achieve full remission. Under these circumstances, knowledge about predictors is essential for the clinician in order to make reliable treatment recommendations. The primary aim of this study was to investigate clinical, demographic, and therapy process-related predictors of Internet-based CBT for severe health anxiety. We performed three types of analyses on data from a sample comprising participants (N = 81) who had received Internet-based CBT in a randomized controlled trial. Outcomes were a) end state health anxiety, b) improvement in health anxiety (continuous change scores), and c) clinically significant improvement. Outcomes were assessed at six-month follow-up. The results showed that the most stable predictors of both end state health anxiety and improvement were baseline health anxiety and depressive symptoms. Treatment adherence, i.e. the number of completed treatment modules, also significantly predicted outcome. Notably, health anxiety at baseline was positively associated with symptom improvement while depressive symptoms was negatively related to improvement. Demographic factors were largely without significant impact on end state symptoms or improvement. We conclude that baseline symptom burden and adherence to treatment have strong predictive effects in Internet-based CBT for severe health anxiety., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

According to cognitive-behavioral models of social anxiety disorder (SAD), four of the important maintaining mechanisms are avoidance, self-focused attention, anticipatory processing and post-event cognitive processing. Individual cognitive therapy (ICT) and cognitive behavioral group therapy (CBGT) both have substantial empirical support. However, it is unclear whether they achieve their effects by similar or different mechanisms. The aim of this study was to investigate whether changes in the four maintenance processes mediate clinical improvement in ICT and CBGT for SAD. We analyzed data from participants (N = 94) who received either ICT or CBGT in two separate RCTs. The results showed that ICT had larger effects than CBGT on social anxiety and each of the four potential mediators. More pertinently, moderated mediation analyses revealed significant between-treatment differences. Whereas improvement in ICT was mainly mediated by reductions in avoidance and self-focused attention, improvement in CBGT was mediated by changes in self-focused attention and in anticipatory and post-event processing. These results support the importance of the putative mediators, but suggest that their relative weights are moderated by treatment type., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Study Objective: To investigate the facial cues by which one recognizes that someone is sleep deprived versus not sleep deprived., Design: Experimental laboratory study., Setting: Karolinska Institutet, Stockholm, Sweden., Participants: Forty observers (20 women, mean age 25 ± 5 y) rated 20 facial photographs with respect to fatigue, 10 facial cues, and sadness. The stimulus material consisted of 10 individuals (five women) photographed at 14:30 after normal sleep and after 31 h of sleep deprivation following a night with 5 h of sleep., Measurements: Ratings of fatigue, fatigue-related cues, and sadness in facial photographs., Results: The faces of sleep deprived individuals were perceived as having more hanging eyelids, redder eyes, more swollen eyes, darker circles under the eyes, paler skin, more wrinkles/fine lines, and more droopy corners of the mouth (effects ranging from b = +3 ± 1 to b = +15 ± 1 mm on 100-mm visual analog scales, P < 0.01). The ratings of fatigue were related to glazed eyes and to all the cues affected by sleep deprivation (P < 0.01). Ratings of rash/eczema or tense lips were not significantly affected by sleep deprivation, nor associated with judgements of fatigue. In addition, sleep-deprived individuals looked sadder than after normal sleep, and sadness was related to looking fatigued (P < 0.01)., Conclusions: The results show that sleep deprivation affects features relating to the eyes, mouth, and skin, and that these features function as cues of sleep loss to other people. Because these facial regions are important in the communication between humans, facial cues of sleep deprivation and fatigue may carry social consequences for the sleep deprived individual in everyday life.

Sleepiness is linked to accidents and reduced performance, and is usually attributed to short/poor prior sleep and sleepiness. However, while the link between reduced sleep and subsequent sleepiness is well established in laboratory experiments of sleep reduction, very little is known about the day-to-day variation of sleepiness in everyday life and its relation to the immediately preceding sleep episode. The purpose of the present study was to investigate the characteristics of this relation across 42 consecutive days. Fifty volunteers participated. Self-reports of sleep were given in the morning and recorded with actigraphy; health was rated in the evening; and sleepiness was rated at eight points during the day (on a scale of 1-9). Results from mixed-model regression analyses showed that, on average, total sleep time predicted sleepiness during the rest of the day across the 42 days, with sleepiness increasing with shorter preceding sleep (β = -0.15 units h(-1) , P < 0.001). Sleepiness also increased with earlier time of rising and lower-rated sleep quality. Days off reduced sleepiness, but was accounted for by sleep. Self-rated health improved when sleepiness was low during the same day (β = -0.36 unit unit(-1) of rated health, P < 0.001), but the two were measured simultaneously. Napping was related to high sleepiness during the same day. Actigraphy measures of sleep duration showed similar, but somewhat weaker, effects than diary measures. It was concluded that the main determinants of daytime sleepiness in a real-life day-to-day context were short sleep, poor sleep and early rising, and that days with high sleepiness ended with ratings of poorer health., (© 2012 European Sleep Research Society.)

Background: Both atopic diseases and sleep disturbances have increased during recent decades, especially in children. Sleep is important for many aspects of immune regulation relevant in allergic diseases, and sleep disturbances are common in patients with such diseases. A connection between sleep disturbances and fatigue, and atopic disease is well established. However, the time course and putative causal relationships between these factors are obscure., Objective: We aimed at investigating the developmental relationships between subjectively reported sleep disturbances and symptoms of atopic disease, from childhood to adolescence., Methods: This longitudinal study used parent-report questionnaire data on symptoms of atopic disease, and sleep disturbances, from the Twin Study of Child and Adolescent Development (TCHAD). Overall, 1480 twin pairs born in Sweden were approached first when children were 8-9 years old, and again later at 13-14 years old. Response rates were 75% and 72%. Data from the TCHAD questionnaires were linked to the Swedish Medical Birth Register based on personal identification numbers., Results: Being overtired at age 8 increased the risk [OR; 95% CI (2.59; 1.31-5.11)] to develop rhinitis symptoms at age 13, even when controlling for gender, previous rhinitis, Socio-economic status, birth weight and other sleep disturbances at age 8. Likewise, symptoms of asthma at age 8 was an independent risk factor for being overtired at age 13 [OR; 95% CI (2.64; 1.44-4.84)], controlling for similar confounders., Conclusion & Clinical Relevance: The findings from this study are consonant with the proposition that atopic disease and disturbed sleep are more than passively interrelated. Future research needs to delineate whether causal relationships between these problems are at hand and, if so, at what periods in development this applies. These results point to a need for clinicians to investigate sleep difficulties and treat impaired sleep in paediatric patients with atopic disease., (© 2013 Blackwell Publishing Ltd.)

Poor subjective health has been associated with higher levels of inflammatory cytokines. We investigated whether such an association would apply to women of the general population. Levels of cytokines, affect and subjective health were assessed in 347 women of the general population aged 45 to 90 years. Higher levels of interleukin-6 were associated with poor subjective health, especially in participants over 65 years of age. Positive affect was a more robust determinant of subjective health than negative affect. The presence of low-grade inflammation and absence of positive affect, rather than presence of negative affect, may be important determinants of subjective health.

Despite the existing knowledge regarding the neuropathology of Alzheimer's disease (AD), the cause of sporadic forms of the disease is unknown. It has been suggested that systemic inflammation may have a role, but the exact mechanisms through which inflammatory processes influence the pathogenesis and progress of AD are not obvious. Allergy is a chronic inflammatory disease affecting more than 20% of the Western population, but the effects of allergic conditions on brain functions are largely unknown. The aim of this study was to investigate whether or not chronic peripheral inflammation associated with allergy affects the expression of AD-related proteins and inflammatory markers in the brain. On the basis of previously described models for allergy in mice we developed a model of chronic airway allergy in mouse, with ovalbumin as allergen. The validity of the chronic allergy model was confirmed by a consistent and reproducible eosinophilia in the bronchoalveolar lavage (BAL) fluid of allergic animals. Allergic mice were shown to have increased brain levels of both immunoglobulin (Ig) G and IgE with a widespread distribution. Allergy was also found to increase phosphorylation of tau protein in the brain. The present data support the notion that allergy-dependent chronic peripheral inflammation modifies the brain inflammatory status, and influences phosphorylation of an AD-related protein, indicating that allergy may be yet another factor to be considered for the development and/or progression of neurodegenerative diseases such as AD., (© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.)

Background/objectives: The connection between stress and sleep is well established in cross-sectional questionnaire studies and in a few prospective studies. Here, the intention was to study the link between stress and sleep on a day-to-day basis across 42 days., Methods: Fifty participants kept a sleep/wake diary across 42 days and responded to daily questions on sleep and stress. The results were analyzed with a mixed model approach using stress during the prior day to predict morning ratings of sleep quality., Results: The results showed that bedtime stress and worries were the main predictors of sleep quality, but that, also, late awakening, short prior sleep, high quality of prior sleep, and good health the prior day predicted higher sleep quality., Conclusions: Stress during the day predicts subsequent sleep quality on a day-to-day basis across 42 days. The observed range of variation in stress/worries was modest, which is why it is suggested that the present data underestimates the impact of stress on subsequent sleep quality., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Problem: This study investigates whether affectivity differs between mothers delivering preterm and term and whether maternal and umbilical cord serum cytokines differ between these groups. Further, whether there are associations between mothers' emotions and maternal and cord cytokines at preterm and term birth., Method of Study: Twenty-seven mothers delivering preterm and 37 mothers delivering at term reported positive/negative affect and previous depressive symptoms during pregnancy. Blood samples from mothers in labor and cord samples (23 preterm and 33 term) were analyzed for cytokines., Results: Maternal IL-8 was lower at preterm delivery compared with term. In the preterm group only, associations were found between negative emotions and maternal IL-6, IL-8 and cord IL-6, IL-8, IL-10, IL-13, and IL-18., Conclusion: The findings indicate associations in preterm delivery between negative emotions and both maternal and neonate immune activity. Future studies should investigate whether such associations are part of the etiology of preterm delivery., (© 2011 John Wiley & Sons A/S.)

Background: Serotonin (5-HT) is highly involved in pain regulation and serotonin-1A (5-HT1A) receptors are important in determining central 5-HT tone. Accordingly, variation in the 5-HT1A receptor gene (HTR1A) may contribute to inter-individual differences in human pain sensitivity. The minor G-allele of the HTR1A single nucleotide polymorphism (SNP) rs6295 attenuates firing of serotonergic neurons and reduces postsynaptic expression of the receptor. Experiments in rodents suggest that 5-HT1A-agonism modulates pain in opposite directions at mild compared to high noxious intensities. Based upon this and several other similar observations, we hypothesized that G-carriers would exhibit a relative hypoalgesia at mild thermal stimuli but tend towards hyperalgesia at higher noxious intensities., Methods: Fourty-nine healthy individuals were selectively genotyped for rs6295. Heat- and cold-pain thresholds were assessed along with VAS-ratings of a range of suprathreshold noxious heat intensities (45°C-49°C). Nociceptive-flexion reflex (NFR) thresholds were also assessed., Results: Volunteers did not deviate significantly from Hardy-Weinberg equilibrium. G-carriers were less sensitive to threshold-level thermal pain. This relative hypoalgesia was abolished at suprathreshold noxious intensities where G-carriers instead increased their ratings of heat-pain significantly more than C-homozygotes. No differences with regard to NFR-thresholds emerged., Conclusion/significance: To the best of our knowledge this is the first study of human pain perception on the basis of variation in HTR1A. The results illustrate the importance of including a range of stimulus intensities in assessments of pain sensitivity. In speculation, we propose that an attenuated serotonergic tone may be related to a 'hypo- to hyperalgesic' response-pattern. The involved mechanisms could be of clinical interest as variation in pain regulation is known to influence the risk of developing pain pathologies. Further investigations are therefore warranted.

Increasing evidence suggests a role of the immune system in modulation of cognition, but details on affected memory systems are largely lacking. We therefore aimed to study the relation between selected cytokines and subsets of memory, and the impact of age in these relations. From a random population-based sample (the Betula Prospective Cohort Study), 298 women (age 45-90) were studied in terms of episodic recall and recognition, semantic fluency and knowledge, and prospective memory. Circulating cytokines of relevance for cognition and aging were measured with ELISA. Levels of interleukin (IL)-6 and sIL-2R were significantly and negatively associated with most cognitive variables, while the opposite was true for IL-1β. Age shared substantial variance with both cytokines and memory, and turned most correlations non-significant when controlled for together with education, BMI and presence of disease. Interactions between age and cytokines were further analyzed in multiple regressions. For IL-6, significant negative interactions with age were found for semantic fluency (p<0.05) and prospective memory (p<0.01), and for sIL-2R in predicting semantic knowledge (p<0.05), indicating an increased negative impact of these cytokines on memory with increasing age. In conclusion, the study indicates a relation between cytokines and memory that appears to be largely mediated by age, and supports the suggestion that cytokine dysregulation with higher age may interact with cognitive aging., (© 2011 The Authors. Scandinavian Journal of Psychology © 2011 The Scandinavian Psychological Associations.)

Background: It is not known whether or not delivering acupuncture triggers mechanisms cited as placebo and if acupuncture or sham reduces radiotherapy-induced emesis more than standard care., Methodology/principal Findings: Cancer patients receiving radiotherapy over abdominal/pelvic regions were randomized to verum (penetrating) acupuncture (n = 109; 99 provided data) in the alleged antiemetic acupuncture point PC6 or sham acupuncture (n = 106; 101 provided data) performed with a telescopic non-penetrating needle at a sham point 2-3 times/week during the whole radiotherapy period. The acupuncture cohort was compared to a reference cohort receiving standard care (n = 62; 62 provided data). The occurrence of emesis in each group was compared after a mean dose of 27 Gray. Nausea and vomiting were experienced during the preceding week by 37 and 8% in the verum acupuncture group, 38 and 7% in the sham acupuncture group and 63 and 15% in the standard care group, respectively. The lower occurrence of nausea in the acupuncture cohort (verum and sham) compared to patients receiving standard care (37% versus 63%, relative risk (RR) 0.6, 95 % confidence interval (CI) 0.5-0.8) was also true after adjustment for potential confounding factors for nausea (RR 0.8, CI 0.6 to 0.9). Nausea intensity was lower in the acupuncture cohort (78% no nausea, 13% a little, 8% moderate, 1% much) compared to the standard care cohort (52% no nausea, 32% a little, 15% moderate, 2% much) (p = 0.002). The acupuncture cohort expected antiemetic effects from their treatment (95%). Patients who expected nausea had increased risk for nausea compared to patients who expected low risk for nausea (RR 1.6; Cl 1.2-2.4)., Conclusions/significance: Patients treated with verum or sham acupuncture experienced less nausea and vomiting compared to patients receiving standard care, possibly through a general care effect or due to the high level of patient expectancy., Trial Registration: ClinicalTrials.gov NCT00621660.

Purpose: upper respiratory tract infection (URTI) is the most common reason for seeking primary care in many countries. Still, little is known about potential strategies to reduce susceptibility. We investigated the relationships between physical activity level, perceived stress, and incidence of self-reported URTI., Methods: we conducted a population-based prospective cohort study of 1509 Swedish men and women aged 20-60 yr with a follow-up period of 4 months. We used a Web-based questionnaire to assess disease status and lifestyle factors at the start of the study. We assessed physical activity and inactivity as total MET-hours (MET task) per day and perceived stress by the 14-item Perceived Stress Scale. Participants were contacted every 3 wk via e-mail to assess incidence of URTI. They reported a total of 1181 occurrences of URTI. We used Poisson regression models to control for age, sex, and other potential confounding factors., Results: we found that high levels of physical activity (≥ 55 MET·h·d) were associated with an 18% reduced risk (incidence rate ratio (IRR) = 0.82, 95% confidence interval (CI) = 0.69-0.98) of self-reporting URTI compared with low levels of physical activity (<45 MET·h·d). This association was stronger among those reporting high levels of stress (IRR = 0.58, 95% CI = 0.43-0.78), especially among men (IRR = 0.37, 95% CI = 0.24-0.59), but absent in the group with low levels of stress., Conclusions: we found that high physical activity was associated with a lower risk of contracting URTI for both men and women. In addition, we found that highly stressed people, particularly men, appear to benefit more from physical activity than those with lower stress levels.

Background: Prenatal factors such as prenatal psychological stress might influence the development of childhood asthma., Methodology and Principal Findings: We assessed the association between maternal bereavement shortly before and during pregnancy, as a proxy for prenatal stress, and the risk of childhood asthma in the offspring, based on two samples of children 1-4 (n = 426,334) and 7-12 (n = 493,813) years assembled from the Swedish Medical Birth Register. Exposure was maternal bereavement of a close relative from one year before pregnancy to child birth. Asthma event was defined by a hospital contact for asthma or at least two dispenses of inhaled corticosteroids or montelukast. In the younger sample we calculated hazards ratios (HRs) of a first-ever asthma event using Cox models and in the older sample odds ratio (ORs) of an asthma attack during 12 months using logistic regression. Compared to unexposed boys, exposed boys seemed to have a weakly higher risk of first-ever asthma event at 1-4 years (HR: 1.09; 95% confidence interval [CI]: 0.98, 1.22) as well as an asthma attack during 12 months at 7-12 years (OR: 1.10; 95% CI: 0.96, 1.24). No association was suggested for girls. Boys exposed during the second trimester had a significantly higher risk of asthma event at 1-4 years (HR: 1.55; 95% CI: 1.19, 2.02) and asthma attack at 7-12 years if the bereavement was an older child (OR: 1.58; 95% CI: 1.11, 2.25). The associations tended to be stronger if the bereavement was due to a traumatic death compared to natural death, but the difference was not statistically significant., Conclusions/significance: Our results showed some evidence for a positive association between prenatal stress and childhood asthma among boys but not girls.

Background: The underlying pathophysiology of eating disorders (ED) is dependent on complex interactions between psychological, biological and social factors. The purpose of the present study was to examine a possible increase in cytokines indicating inflammation, as measured by tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in ED patients, and to explore possible relationships between cytokines and self-reported personality traits., Methods: Female patients with severe ED (n = 26) were recruited consecutively from an inpatient clinic and were compared to age-matched healthy females (n = 12). Commercial ELISA tests developed for the measurement of serum levels of TNF-α and IL-6 were employed. Personality traits were measured using Karolinska Scales of Personality., Results: The patient group displayed increased levels of the cytokine TNF-α and a tendency towards increased IL-6 levels. Spearman's rank correlation coefficient was used to examine possible relationships between levels of cytokines and personality traits. The results showed that IL-6 levels were positively related to both somatic and psychic anxiety and to aggression scales, such as irritability and suspicion. Increased levels of TNF-α, in turn, were significantly correlated with high scores on the depression-related anxiety scale Inhibition of Aggression. However, increased levels of cytokines in the ED group did not seem to be mainly associated with symptoms of depression., Conclusion: We cannot rule out the possibility that comorbid conditions in the group contribute to the higher cytokine values. Further studies need to explore the possible influence of cytokines on the severity of ED and whether this might be mediated or moderated by specific personality traits., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To evaluate the effect of acupressure administered during the active phase of labor on nulliparous women's ratings of labor pain., Design: Randomized controlled trial., Setting: Public hospital in India., Sample: Seventy-one women randomized to receive acupressure at acupuncture point spleen 6 (SP6) on both legs during contractions over a 30-minute period (acupressure group), 71 women to receive light touch at SP6 on both legs during the same period of time (touch group) and 70 women to receive standard care (standard care group)., Methods: Experience of in-labor pain was assessed by visual analog scale at baseline before treatment, immediately after treatment, and at 30, 60 and 120 minutes after treatment., Main Outcome Measure: Labor pain intensity at different time intervals after treatment compared with before treatment., Results: A reduction of in-labor pain was found in the acupressure group and was most noticeable immediately after treatment (acupressure group vs. standard care group p < 0.001; acupressure group vs. touch group p < 0.001)., Conclusion: Acupressure seems to reduce pain during the active phase of labor in nulliparous women giving birth in a context in which social support and epidural analgesia are not available. However, the treatment effect is small which suggests that acupressure may be most effective during the initial phase of labor.

Objectives: The primary aim of this study was to compare the retrieval of autobiographical memory and the social problem-solving performance of individuals with borderline personality disorder (BPD) and a history of suicide attempts, with and without concurrent diagnoses of depression and/or post-traumatic stress disorder (PTSD), to that of controls. Additionally, the relationships between autobiographical memory, social problem-solving skills, and various clinical characteristics were examined in the BPD group., Design: Individuals with BPD who had made at least two suicide attempts were compared to controls with regard to specificity of autobiographical memory and social problem-solving skills. Autobiographical memory specificity and social problem-solving skills were further studied in the BPD group by comparing depressed participants to non-depressed participants; and autobiographical memory specificity was also studied by comparing participants with and without PTSD., Method: A total of 47 women with a diagnosis of BPD and 30 controls completed the Autobiographical Memory Test, assessing memory specificity, and the means-end problem solving-procedure, measuring social problem-solving skills. The prevalence of suicidal/self-injurious behaviour, and the exposure to violence, was also assessed in the BPD group., Results: Compared to controls, participants with BPD showed reduced specificity of autobiographical memory, irrespective of either concurrent depression, previous depression, or concurrent PTSD. The depressed BPD group displayed poor problem-solving skills. Further, an association between unspecific memory and poor problem-solving was displayed in the BPD group., Conclusion: Our results confirmed that reduced specificity of autobiographical memory is an important characteristic of BPD individuals with a history of suicide attempt, independent of depression, or PTSD. Reduced specificity of autobiographical memory was further related to poor social problem-solving capacity in the BPD group.

Background: As an important mediator by which the brain receives information about the body's energy state, leptin may be associated with subjectively perceived health., Objective: The main aim of the present study was to investigate concurrent and prospective associations between leptin and self-rated health (SRH), a strong predictor of morbidity and mortality, in a random population sample. An additional aim was to examine whether sick leave was associated with leptin and poor SRH., Methods: In a prospective, population-based cohort study in Sweden, men and women underwent a medical examination in 1998, at which time blood was drawn and participants were asked to respond to a questionnaire concerning demographics, health behavior, and psychosocial factors. In 2000, the participants responded to a second questionnaire sent by postal mail. Spearman rank correlations were used to investigate the relationships between leptin, SRH, sick leave, and background variables. Partial Spearman coefficients were then calculated to investigate the patterns of association between leptin, SRH, and sick leave independent of age, body mass index (BMI), presence of diagnosis, and testosterone or estradiol., Results: A total of 98 men and 104 women, aged 23 to 76 years, and 91 men and 96 women at follow-up, participated in the study. In men, relatively higher levels of leptin were prospectively associated with relatively worse SRH (rho = 0.20; P = 0.05), but the relationship was not significant in the cross-sectional analysis (rho = 0.18; P = 0.07). This association was not found in women. When controlling for age, BMI, presence of diagnosis, and testosterone, higher levels of leptin were associated with poor SRH in men in cross-sectional analysis (rho = 0.27; P < 0.01) but not prospectively. In women, leptin was not associated with SRH in cross-sectional analysis, but relatively higher levels were prospectively associated with better SRH when adjusted for background factors and estradiol (rho = -0.26; P < 0.05). SRH was independently associated with future sick leave in both men (rho = 0.34; P < 0.01) and women (rho = 0.30; P < 0.05), whereas no association between leptin and future sick leave was found., Conclusions: Contrasting associations were found between men and women in the relationship between leptin and SRH. Based on the finding that higher leptin levels were associated with better SRH in women than in men, along with corroboration from recent studies, we propose that leptin may serve different psychobiological functions in men than in women., (Copyright (c) 2010 Excerpta Medica Inc. All rights reserved.)

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels., Methods: 136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 +/- 87 nmol/24 h) and the 10 with the lowest UFC (168 +/- 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 microg/1.73 m(2)) of ACTH challenge and after 2 weeks' exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in a whole-blood assay., Results: After exposure to DEX in vivo, inhibition of IL-6 and TNF-alpha decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1beta and IL-6, both compared to the high-cortisol group and their own baseline levels., Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels., (Copyright 2009 S. Karger AG, Basel.)

Background: Recent findings indicate that atopics may be more vulnerable to stress than non-atopics. However, the roles of psychological well-being and sleep in this presumed increased sensitivity are not known., Purpose: To investigate the effects of a brief naturalistic stressor on psychological responses, sleep, and allergic symptoms and to compare those responses between atopic and non-atopic individuals., Methods: We assessed atopic and non-atopic students during a period without and during a period with examinations., Results: For both atopic and non-atopic students, tension, anxiety, and depression deteriorated in response to examination, as did sleep latency and sleep quality. Overall, atopics were more tense, had more anxiety, longer sleep latencies, and were less well rested than non-atopics. Non-atopic students rose from bed later during the examination period. In response to examination, atopic students reported increased frequency of stress behaviors (e.g., eating fast), while decreased stress behaviors were reported by non-atopic students. Allergic symptoms were not affected., Conclusion: Atopic students were worse off in aspects of psychological well-being and sleep, but displayed only partly stronger responses to a stressor compared to non-atopic students. In spite of a broad negative response to examination, allergic symptoms were not affected.

Immunotherapy is being increasingly utilized for adjuvant treatment for breast cancer (BC). We have previously described immune functions during primary therapy for BC. The present study describes immune recovery patterns during long-term, unmaintained follow-up after completion of adjuvant therapy.A group of patients with primary BC had been treated with adjuvant radio-chemotherapy (RT + CT) 5-fluorouracil, epirubicin and cyclophosphamide (FEC) (n = 21) and another group with radiotherapy (RT) (n = 20) alone. Immunological testing of NK and T-cell functions was performed initially at the end of adjuvant treatment and repeated after 2, 6 and 12 months. NK cell cytotoxicity was significantly higher (P < 0.05) at all time-points in patients than in age-matched controls and did not differ between the two treatments groups during one year observation. In contrast, lower numbers of CD4 T-cells and lower expression of CD28 on T-cells was observed particularly in RT + CT patients and did not normalize during the observation period. The numbers of T(reg) cells (CD4(+)CD25(high)) were low in the RT + CT group during follow-up, as well as expression of TCRxi, Zap70, p56(lck), P59(fyn) and PI3 k in CD4(+) cells. In contrast, expression of intracellular cytokines (IFN-gamma, IL-2, IL-4) in CD4 and CD8 T cells were significantly higher in RT + CT patients than in the RT group and the difference increased during follow-up. In conclusion, NK-cell cytotoxicity increased during unmaintained long-term follow-up whereas CD4 and regulatory T cells as well as signal transduction molecules remained low following adjuvant radio-chemotherapy.

Background: Prolonged psychosocial stress is a condition assessed through self-reports. Here we aimed to identify biochemical markers for screening and early intervention in women., Methods: Plasma concentrations of interleukin (IL) 1-alpha, IL1-beta, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (INF-gamma), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), prolactin, and testosterone were measured in: 195 women on long-term sick-leave for a stress-related affective disorder, 45 women at risk for professional burnout, and 84 healthy women., Results: We found significantly increased levels of MCP-1, VEGF and EGF in women exposed to prolonged psychosocial stress. Statistical analysis indicates that they independently associate with a significant risk for being classified as ill., Conclusions: MCP-1, EGF, and VEGF are potential markers for screening and early intervention in women under prolonged psychosocial stress.

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.

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.

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.

Background: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown., Objective: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals., Methods: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed., Results: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress., Conclusion: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.

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.

In order to evaluate a structured support intervention programme, symptoms and quality of life (QOL) were studied in 61 consecutive cancer patients with different tumour diagnoses in relation to intervention and follow-up. The majority of the patients were female. The Edmonton symptom assessment scale (ESAS), the Norwegian fatigue questionnaire and the hospital anxiety and depression scale (HADS) were used. Data were analysed according to ANOVA and Tukey's honest significant difference (HSD) test. ESAS sickness score (P=0.0001), depression (P=0.0001), anxiety (P=0.0001) and QOL (P=0.0009) improved and the improvements in depression and anxiety were still significant after 3 months (P=0.02 respectively). Aspects of fatigue also improved significantly in 7 of 11 questions after the intervention (P< or =0.04) but these improvements were not observed after 3 months. Anxiety according to the HADS questionnaire improved significantly after the intervention (P=0.0006). The majority of the patients highly appreciated the possibility of sharing thoughts and troubles with others with similar experiences (59%). The programme was therefore found to improve QOL, and physical and psychological functions. Randomized studies in relation to immunological changes and follow-up are in progress.

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 night's 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.

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)., Subjects and Methods: Consecutive women patients who survived hospitalization for acute myocardial infarction, and/or underwent a percutaneous transluminal coronary angioplasty or a coronary artery bypass grafting were included and evaluated in a stable condition 1 year after the index events. An ambulatory 24-h ECG was recorded during normal activities. SDNN index (mean of the standard deviations of all normal to normal intervals for all 5-min segments of the entire recording) and the following frequency domain parameters were assessed: total power, high frequency (HF) power, low frequency (LF) power and very low frequency (VLF) power. Levels of high-sensitivity CRP were measured by nephelometry, IL-6 and IL-1ra concentrations were determined by enzyme immunoassay., Results: Levels of IL-6 showed an inverse relation with HRV measures even after controlling for potential confounding factors. The P-values were 0.02, 0.04, 0.01, 0.03, 0.18 for the multivariate association with SDDN index, total power, VLF power, LF power and HF power respectively. In contrast, the inverse relationship between HRV measures and CRP or IL-1ra levels were weak and nonsignificant. Correlation coefficients for the relationship between IL-6 and HRV measures were both uni- and multivariately higher than for the relationship between HRV measures and any other factors evaluated in this study., Conclusion: Concentration of IL-6 showed a negative, independent association with HRV in women with CHD. Thus, increased inflammatory activity, as reflected by IL-6 levels, may represent a new auxiliary mechanism linking decreased HRV to poor prognosis in CHD.

The article consists in a review of the evidence of psychological and neural influences on the aetiology and severity of allergy. Histamine release in response to symbolic stimuli and behavioural conditioning of allergy-related immune variables suggest the existence of links via which psychological factors can affect the allergic cascade. Although this has been established in animal species, and is supported by evidence of neuro-immune communication pathways, convincing evidence of its occurrence in humans is sparse. Although asthma and stress symptoms seem to be related, the causal direction of such relationship remains unclear. In view of the occurrence of undocumented allergy and the importance of symptom perception as a basis for optimal medication, the assessment of subjective allergy symptoms is a cogent issue.

To study brain-immune relations, we correlated positron emission tomographic (PET) measures of regional cerebral blood flow (rCBF) with immune measures in 10 female volunteers. The natural killer (NK) activity correlated negatively with activity bilaterally in the secondary sensory cortex, whereas the Concanavalin A (Con A) response correlated positively with rCBF bilaterally in secondary visual, motor, and sensory cortices, the thalamus, the putamen, and the left hippocampus. Although representing preliminary data from a small number of subjects, these observations provide further support for the presence of interactions between the brain and the immune system., (Copyright 1998 Academic Press.)

Social support and immune status were assessed in women treated with adjuvant chemotherapy for breast cancer. Perception of enhanced attachment was associated with an increased number of white blood cell levels three months after, but not during, chemotherapy. After treatment, patients with high attachment ratings had higher numbers and proportions of granulocytes, and lower proportions of lymphocytes and monocytes. It is concluded that the support experienced by a cancer patient can be associated with counts and proportions of leukocytes, but that this effect, if present during chemotherapy, is overridden by the biological factor that affects the haematopoetic process.

Immune parameters were assessed in 22 women before chemotherapy for ovarian cancer and compared with assessment made at home 2 days earlier. In the hospital, as compared to home measures, patients had a lower percentage of lymphocytes and monocytes and a higher percentage of granulocytes. Absolute numbers of lymphocytes were lower at the hospital as compared to at home. T-cell proliferative responses to concanavalin A were elevated for cells isolated from hospital blood samples as compared to home samples. The observed changes in immune parameters were not related to levels o r state anxiety at home or at the hospital. The results show anticipatory immune changes in a group of patients receiving chemotherapy that did not include cyclophosphamide.