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author:("leander, Mats")
1.  Personality Change following Internet-Based Cognitive Behavior Therapy for Severe Health Anxiety 
PLoS ONE  2014;9(12):e113871.
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)
doi:10.1371/journal.pone.0113871
PMCID: PMC4250052  PMID: 25437150
2.  Sleep Polysomnography and Reported Stress Across 6 Weeks 
Industrial Health  2013;52(1):36-42.
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.
doi:10.2486/indhealth.2013-0169
PMCID: PMC4202771  PMID: 24292880
Polysomnography; Subjective ratings; EEG; Diary
3.  Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/ T Helper 2 Balance in Humans 
PLoS ONE  2013;8(12):e82291.
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.
doi:10.1371/journal.pone.0082291
PMCID: PMC3859577  PMID: 24349251
4.  Mediators in Internet-Based Cognitive Behavior Therapy for Severe Health Anxiety 
PLoS ONE  2013;8(10):e77752.
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.
doi:10.1371/journal.pone.0077752
PMCID: PMC3798404  PMID: 24147073
5.  Serotonin-1A Receptor Polymorphism (rs6295) Associated with Thermal Pain Perception 
PLoS ONE  2012;7(8):e43221.
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.
doi:10.1371/journal.pone.0043221
PMCID: PMC3432037  PMID: 22952650
6.  Efficacy of a behavioral self-help treatment with or without therapist guidance for co-morbid and primary insomnia -a randomized controlled trial 
BMC Psychiatry  2012;12:5.
Background
Cognitive behavioral therapy is treatment of choice for insomnia, but availability is scarce. Self-help can increase availability at low cost, but evidence for its efficacy is limited, especially for the typical insomnia patient with co-morbid problems. We hypothesized that a cognitive behaviorally based self-help book is effective to treat insomnia in individuals, also with co-morbid problems, and that the effect is enhanced by adding brief therapist telephone support.
Methods
Volunteer sample; 133 media-recruited adults with insomnia. History of sleep difficulties (mean [SD]) 11.8 [12.0] years. 92.5% had co-morbid problems (e.g. allergy, pain, and depression). Parallel randomized (block-randomization, n ≥ 21) controlled "open label" trial; three groups-bibliotherapy with (n = 44) and without (n = 45) therapist support, and waiting list control (n = 44). Assessments before and after treatment, and at three-month follow-up. Intervention was six weeks of bibliotherapeutic self-help, with established cognitive behavioral methods including sleep restriction, stimulus control, and cognitive restructuring. Therapist support was a 15-minute structured telephone call scheduled weekly. Main outcome measures were sleep diary data, and the Insomnia Severity Index.
Results
Intention-to-treat analyses of 133 participants showed significant improvements in both self-help groups from pre to post treatment compared to waiting list. For example, treatment with and without support gave shorter sleep onset latency (improvement minutes [95% Confidence Interval], 35.4 [24.2 to 46.6], and 20.6 [10.6 to 30.6] respectively), and support gave a higher remission rate (defined as ISI score below 8; 61.4%), than bibliotherapy alone (24.4%, p's < .001). Improvements were not seen in the control group (sleep onset latency 4.6 minutes shorter [-1.5 to 10.7], and remission rate 2.3%). Self-help groups maintained gains at three-month follow-up.
Conclusions
Participants receiving self-help for insomnia benefited markedly. Self-help, especially if therapist-supported, has considerable potential to be as effective as individual treatment at lower cost, also for individuals with co-morbid problems.
Trial Registration
ClinicalTrials.gov: NCT01105052
doi:10.1186/1471-244X-12-5
PMCID: PMC3328261  PMID: 22264332
7.  Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro 
Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation.
However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.
doi:10.1186/1744-9081-7-47
PMCID: PMC3247862  PMID: 22098673
associative learning; conditioning; habituation; in vitro; monocyte; macrophage; lipopolysaccharide; streptomycin; interleukin-6
8.  Maternal Bereavement and Childhood Asthma—Analyses in Two Large Samples of Swedish Children 
PLoS ONE  2011;6(11):e27202.
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.
doi:10.1371/journal.pone.0027202
PMCID: PMC3210147  PMID: 22087265
9.  Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care 
PLoS ONE  2011;6(3):e14766.
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
doi:10.1371/journal.pone.0014766
PMCID: PMC3063156  PMID: 21448267
10.  Beauty sleep: experimental study on the perceived health and attractiveness of sleep deprived people 
Objective To investigate whether sleep deprived people are perceived as less healthy, less attractive, and more tired than after a normal night’s sleep.
Design Experimental study.
Setting Sleep laboratory in Stockholm, Sweden.
Participants 23 healthy, sleep deprived adults (age 18-31) who were photographed and 65 untrained observers (age 18-61) who rated the photographs.
Intervention Participants were photographed after a normal night’s sleep (eight hours) and after sleep deprivation (31 hours of wakefulness after a night of reduced sleep). The photographs were presented in a randomised order and rated by untrained observers.
Main outcome measure Difference in observer ratings of perceived health, attractiveness, and tiredness between sleep deprived and well rested participants using a visual analogue scale (100 mm).
Results Sleep deprived people were rated as less healthy (visual analogue scale scores, mean 63 (SE 2) v 68 (SE 2), P<0.001), more tired (53 (SE 3) v 44 (SE 3), P<0.001), and less attractive (38 (SE 2) v 40 (SE 2), P<0.001) than after a normal night’s sleep. The decrease in rated health was associated with ratings of increased tiredness and decreased attractiveness.
Conclusion Our findings show that sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested. This suggests that humans are sensitive to sleep related facial cues, with potential implications for social and clinical judgments and behaviour. Studies are warranted for understanding how these effects may affect clinical decision making and can add knowledge with direct implications in a medical context.
doi:10.1136/bmj.c6614
PMCID: PMC3001961  PMID: 21156746
11.  Novel Biochemical Markers of Psychosocial Stress in Women 
PLoS ONE  2009;4(1):e3590.
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-α, IL1-β, IL-2, IL-4, IL-6, IL-8, IL-10, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), 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.
doi:10.1371/journal.pone.0003590
PMCID: PMC2627901  PMID: 19177163

Results 1-11 (11)