Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

Smartphone-Supported versus Full Behavioural Activation for Depression: A Randomised Controlled Trial.

BACKGROUND: There is need for more cost and time effective treatments for depression. This is the first randomised controlled trial in which a blended treatment--including four face-to-face sessions and a smartphone application--was compared against a full behavioural treatment. Hence, the aim of the current paper was to examine whether a blended smartphone treatment was non-inferior to a full behavioural activation treatment for depression. METHODS: This was a randomised controlled non-inferiority trial (NCT01819025) comparing a blended treatment (n=46) against a full ten-session treatment (n=47) for people suffering from major depression. Primary outcome measure was the BDI-II, that was administered at pre- and post-treatment, as well as six months after the treatment. RESULTS: Results showed significant improvements in both groups across time on the primary outcome measure (within-group Cohen's d=1.35; CI [-0.82, 3.52] to d=1.47; CI [-0.41, 3.35]; between group d=-0.13 CI [-2.37, 2.09] and d=-0.10 CI [-2.53, 2.33]). At the same time, the blended treatment reduced the therapist time with an average of 47%. CONCLUSIONS: We could not establish whether the blended treatment was non-inferior to a full BA treatment. Nevertheless, this study points to that the blended treatment approach could possibly treat nearly twice as many patients suffering from depression by using a smartphone application as add-on. More studies are needed before we can suggest that the blended treatment method is a promising cost-effective alternative to regular face-to-face treatment for depression. TRIAL REGISTRATION: Cognitive Behavioral Therapy Treatment of Depression With Smartphone Support NCT01819025.

Compartment differences of inflammatory activity in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with local and systemic inflammation. The knowledge of interaction and co-variation of the inflammatory responses in different compartments is meagre. METHOD: Healthy controls (n = 23), smokers with (n = 28) and without (n = 29) COPD performed spirometry and dental examinations. Saliva, induced sputum, bronchoalveolar lavage (BAL) fluid and serum were collected. Inflammatory markers were assessed in all compartments using ELISA, flow cytometry and RT-PCR. RESULTS: Negative correlations between lung function and saliva IL-8 and matrix metalloproteinase-9 (MMP-9) were found in smokers with COPD. IL-8 and MMP-9 in saliva correlated positively with periodontal disease as assessed by gingival bleeding in non-smokers.Tumor necrosis factor-α (TNF-α) in saliva, serum and TNF-α mRNA expression on macrophages in BAL-fluid were lower in smokers than in non-smokers. There were positive correlations between soluble TNF-α receptor 1 (sTNFR1) and soluble TNF-α receptor 2 (sTNFR2) in sputum, BAL-fluid and serum in all groups. Sputum interleukin-8 (IL-8) or interleukin-6 (IL-6) was positively correlated with sTNFR1 or sTNFR2 in non-smokers and with sTNFR2 in COPD. CONCLUSION: Saliva which is convenient to collect and analyse, may be suitable for biomarker assessment of disease activity in COPD. An attenuated TNF-α expression was demonstrated by both protein and mRNA analyses in different compartments suggesting that TNF-α response is altered in moderate and severe COPD. Shedding of TNFR1 or TNFR2 is similarly regulated irrespective of airflow limitation.

Smoking rate and periodontal disease prevalence: 40-year trends in Sweden 1970-2010.

AIM: To investigate the relationship between smoking rate and periodontal disease prevalence in Sweden. MATERIAL AND METHODS: National smoking rates were found from Swedish National Statistics on smoking habits. Based on smoking rates for the years 1970-2010, periodontal disease prevalence estimates were calculated for the age bracket 40-70 years and smoking-associated relative risks between 2.0 and 20.0. The impact of smoking on the population was estimated according to the concept of population attributable fraction. RESULTS: The age-standardized smoking rate in Sweden declined from 44% in 1970 to 15% in 2010. In parallel with the smoking decline the calculated prevalence estimate of periodontal disease dropped from 26% to 12% assuming a 10-fold smoking-associated relative risk. Even at more moderate magnitudes of the relative risk, e.g. 2-fold or 5-fold, the prevalence decrease was quite tangible, suggesting that the current prevalence in Sweden is about 20-50% of the level 40 years ago. The population attributable fraction, estimating the portion of the disease that would have been avoided in the absence of smoking, was 80% in 1970 and 58% in 2010 at a ten-fold relative risk. CONCLUSION: Calculated estimates of periodontal disease prevalence are closely related to real changes in smoking rate. As smoking rate drops periodontal disease prevalence will drop.

Clinical validation of a non-heteronormative version of the Social Interaction Anxiety Scale (SIAS).

INTRODUCTION: Despite welcomed changes in societal attitudes and practices towards sexual minorities, instances of heteronormativity can still be found within healthcare and research. The Social Interaction Anxiety Scale (SIAS) is a valid and reliable self-rating scale of social anxiety, which includes one item (number 14) with an explicit heteronormative assumption about the respondent's sexual orientation. This heteronormative phrasing may confuse, insult or alienate sexual minority respondents. A clinically validated version of the SIAS featuring a non-heteronormative phrasing of item 14 is thus needed. METHODS: 129 participants with diagnosed social anxiety disorder, enrolled in an Internet-based intervention trial, were randomly assigned to responding to the SIAS featuring either the original or a novel non-heteronormative phrasing of item 14, and then answered the other item version. Within-subject, correlation between item versions was calculated and the two scores were statistically compared. The two items' correlations with the other SIAS items and other psychiatric rating scales were also statistically compared. RESULTS: Item versions were highly correlated and scores did not differ statistically. The two items' correlations with other measures did not differ statistically either. CONCLUSIONS: The SIAS can be revised with a non-heteronormative formulation of item 14 with psychometric equivalence on item and scale level. Implications for other psychiatric instruments with heteronormative phrasings are discussed.

Predictors and moderators of internet- and group-based cognitive behaviour therapy for panic disorder.

Internet-based cognitive behaviour therapy (ICBT) can be equally effective as traditional face-to-face cognitive behaviour therapy (CBT) for treating panic disorder (PD). However, little is known about the predictors and moderators of outcome of ICBT when delivered in psychiatric outpatient settings. This study investigated a selection of outcome predictors and moderators of ICBT for panic disorder based on data from a randomised controlled trial where therapist-guided ICBT was compared with group CBT (GCBT) for panic disorder. Participants (N = 104) received 10 weeks of ICBT or GCBT and were assessed before and after treatment, and after six months. Multiple regression analyses were used to test for significant predictors of treatment outcome. Predictors of positive treatment response for both modalities were having low levels of symptom severity and work impairment. In addition, anxiety sensitivity was found to have a small negative relationship with treatment outcome, suggesting that anxiety sensitivity may slightly enhance treatment response. Treatment modality had a moderating effect on the relationship between domestic impairment and outcome and on the relationship between initial age of onset of panic symptoms and treatment outcome, favouring ICBT for patients having had an early onset of PD symptoms and for patients having a high domestic functional impairment. These results suggest that both ICBT and GCBT are effective treatment modalities for PD and that it is possible to predict a significant proportion of the long-term outcome variance based on clinical variables.

Dental health in smokers with and without COPD.

The association between chronic obstructive pulmonary disease (COPD) and periodontal disease is sparsely studied. The aim was to describe the co-variation of periodontitis and lung function impairment in smokers. The hypothesis was that the destructive processes in the mouth and the lungs are interdependent due to a general individual susceptibility to detrimental effects of tobacco smoke. Smokers with COPD (n = 28) stage II and III according to GOLD guidelines and smokers without COPD (n = 29) and healthy non-smokers (n = 23) participated in the study. The groups of smokers were matched for cumulative exposure to tobacco smoke. Radiographic, general and dental clinical examination, lung function measurements and quality of life (SF-36) assessment were conducted. The relationship between respiratory and dental outcomes was analyzed. Dental health, assessed by plaque, gingival bleeding, periodontal pocket depth and loss of teeth was impaired in the smokers compared with non-smokers with no major differences between smokers with and without COPD. There was, however, a weak correlation between periodontitis and emphysema/impaired diffusion capacity. Impaired quality of life was associated with smoking and impaired lung function but not influenced by dental status. In conclusion periodontitis was strongly associated with smoking, weakly associated with lung tissue destruction and very weakly or even not at all associated with chronic airflow limitation. The results indicate that, although there was a co-variation between periodontitis and pathologic lung processes in smokers, the risk of developing COPD, as defined by spirometric outcomes, is not associated with the risk of impaired dental health in smokers.

The oral cone of Anomalocaris is not a classic ''peytoia''.

The Cambro-Ordovician anomalocaridids are large ecdysozoans commonly regarded as ancestors of the arthropods and apex predators. Predation is indicated partly by the presence of an unusual "peytoia"-type oral cone, which is a tetraradial outer ring of 32 plates, four of which are enlarged and in perpendicular arrangement. This oral cone morphology was considered a highly consistent and defining characteristic of well-known Burgess Shale taxa. It is here shown that Anomalocaris has a different oral cone, with only three large plates and a variable number of smaller and medium plates. Its functional morphology suggests that suction, rather than biting, was used for food ingestion, and that anomalocaridids in general employed a range of different scavenging and predatory feeding strategies. Removing anomalocaridids from the position of highly specialized trilobite predators forces a reconsideration of the ecological structure of the earliest marine animal communities in the Cambrian.

The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met) in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting. METHODS: We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients. RESULTS: We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based) CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material. CONCLUSIONS: We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed. TRIAL REGISTRATION: Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2). Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260.

Internet-versus group-administered cognitive behaviour therapy for panic disorder in a psychiatric setting: a randomised trial.

BACKGROUND: Internet administered cognitive behaviour therapy (CBT) is a promising new way to deliver psychological treatment, but its effectiveness in regular care settings and in relation to more traditional CBT group treatment has not yet been determined. The primary aim of this study was to compare the effectiveness of Internet-and group administered CBT for panic disorder (with or without agoraphobia) in a randomised trial within a regular psychiatric care setting. The second aim of the study was to establish the cost-effectiveness of these interventions. METHODS: Patients referred for treatment by their physician, or self-referred, were telephone-screened by a psychiatric nurse. Patients fulfilling screening criteria underwent an in-person structured clinical interview carried out by a psychiatrist. A total of 113 consecutive patients were then randomly assigned to 10 weeks of either guided Internet delivered CBT (n = 53) or group CBT (n = 60). After treatment, and at a 6-month follow-up, patients were again assessed by the psychiatrist, blind to treatment condition. RESULTS: Immediately after randomization 9 patients dropped out, leaving 104 patients who started treatment. Patients in both treatment conditions showed significant improvement on the main outcome measure, the Panic Disorder Severity Scale (PDSS) after treatment. For the Internet treatment the within-group effect size (pre-post) on the PDSS was Cohen's d = 1.73, and for the group treatment it was d = 1.63. Between group effect sizes were low and treatment effects were maintained at 6-months follow-up. We found no statistically significant differences between the two treatment conditions using a mixed models approach to account for missing data. Group CBT utilised considerably more therapist time than did Internet CBT. Defining effect as proportion of PDSS responders, the cost-effectiveness analysis concerning therapist time showed that Internet treatment had superior cost-effectiveness ratios in relation to group treatment both at post-treatment and follow-up. CONCLUSIONS: This study provides support for the effectiveness of Internet CBT in a psychiatric setting for patients with panic disorder, and suggests that it is equally effective as the more widely used group administered CBT in reducing panic-and agoraphobic symptoms, as well as being more cost effective with respect to therapist time. TRIAL REGISTRATION: ClinicalTrials.gov NCT00845260.

Consensus Report: 2nd European Workshop on Tobacco Use Prevention and Cessation for Oral Health Professionals.

Tobacco use has been identified as a major risk factor for oral disorders such as cancer and periodontal disease. Tobacco use cessation (TUC) is associated with the potential for reversal of precancer, enhanced outcomes following periodontal treatment, and better periodontal status compared to patients who continue to smoke. Consequently, helping tobacco users to quit has become a part of both the responsibility of oral health professionals and the general practice of dentistry. TUC should consist of behavioural support, and if accompanied by pharmacotherapy, is more likely to be successful. It is widely accepted that appropriate compensation of TUC counselling would give oral health professionals greater incentives to provide these measures. Therefore, TUC-related compensation should be made accessible to all dental professionals and be in appropriate relation to other therapeutic interventions. International and national associations for oral health professionals are urged to act as advocates to promote population, community and individual initiatives in support of tobacco use prevention and cessation (TUPAC) counselling, including integration in undergraduate and graduate dental curricula. In order to facilitate the adoption of TUPAC strategies by oral health professionals, we propose a level of care model which includes 1) basic care: brief interventions for all patients in the dental practice to identify tobacco users, assess readiness to quit, and request permission to re-address at a subsequent visit, 2) intermediate care: interventions consisting of (brief) motivational interviewing sessions to build on readiness to quit, enlist resources to support change, and to include cessation medications, and 3) advanced care: intensive interventions to develop a detailed quit plan including the use of suitable pharmacotherapy. To ensure that the delivery of effective TUC becomes part of standard care, continuing education courses and updates should be implemented and offered to all oral health professionals on a regular basis.

Oral health risks of tobacco use and effects of cessation.

The purpose of this paper is to review the epidemiologic evidence for the effects of tobacco use and tobacco use cessation on a variety of oral diseases and conditions. Exposures considered include cigarette and bidi smoking, pipe and cigar smoking, and smokeless tobacco use. Oral diseases and disorders considered include oral cancer and precancer, periodontal disease, caries and tooth loss, gingival recession and other benign mucosal disorders as well as implant failure. Particular attention is given to the impact of tobacco use cessation on oral health outcomes. We conclude that robust epidemiologic evidence exists for adverse oral health effects of tobacco smoking and other types of tobacco use. In addition, there is compelling evidence to support significant benefits of tobacco use cessation with regard to various oral health outcomes. Substantial oral health benefits can be expected from abstention and successful smoking cessation in a variety of populations across all ages.

Periodontal health in children exposed to passive smoking.

AIM: To determine (1) the cotinine levels of saliva, urine and gingival crevicular fluid (GCF) of children in families with and without smoking members and (2) a possible association between the periodontal health of the children and exposure to passive smoking. MATERIAL AND METHODS: The study population comprised of 109 children in the age range 6-12 years. Children were classified as exposed to passive tobacco smoking (PTS-exposed, n=51) and as unexposed controls (PTS-unexposed, n=58). Plaque index, gingival index, bleeding on probing, probing depth and clinical attachment level (CAL) were recorded. GCF, saliva and urine samples were also collected. The levels of cotinine in these fluids were determined by enzyme-linked immunosorbent assay. RESULTS: The mean salivary cotinine concentration was significantly increased in PTS-exposed children compared with PTS-unexposed children (p<0.05). Further, in a dose-dependent way, the mean salivary concentration was significantly higher in children whose father or mother was a smoker (p<0.05) as compared, respectively, with children whose fathers and mothers were non-smokers. The mean CAL was significantly less in PTS-exposed children compared with non-PTS-exposed children (0.09 mm; p<0.05) and also in children whose father was a smoker (p<0.05), but not in children whose mother was a smoker as compared with non-smoker fathers and mothers, respectively. The GCF cotinine levels were below the detection limits with the assay method that was used. CONCLUSIONS: We have observed that children who are exposed to passive smoking have elevated cotinine levels in their saliva concomitant with a lowered CAL.

The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism.

The short allele of a functional polymorphism (5-HTTLPR) in the serotonin transporter (5-HTT) promoter is associated with reduced serotonin transporter expression, lower in vivo 5-HTT binding, higher neuroticism and amygdala reactivity as well as facilitated fear conditioning and is a candidate variant for panic disorder. However, case-control studies have consistently failed to show an association between 5-HTTLPR and panic disorder. As psychiatric disorders are broadly defined phenotypes merging different symptoms to syndromes, they may not be very well suited for genetic association studies. An alternative approach is to measure symptoms along continuous symptom dimensions which may more appropriately reflect their biological underpinnings and may reveal subpopulations within clinical diagnostic groups. We recorded the symptomatic profile in 73 in panic disorder patients using observer-rated instruments (Panic Disorder Severity Scale, PDSS; Montgomery-Asberg Depression Rating Scale, MADRS) and hypothesized more severe symptoms in patients carrying the 5-HTTLPR s-allele. We observed a strong association between bi- and triallelic 5-HTTLPR polymorphisms and the symptomatic profile. Carriers of the 5-HTTLPR s-allele suffered from most severe panic and depressive symptoms. Our data highlight the importance of defining appropriate phenotypes for psychiatric genetic studies and demonstrate that the 5-HTTLPR genotype may be related to the symptomatic profiles rather than to the vulnerability to develop panic disorder.

Morphology of Luolishania longicruris (Lower Cambrian, Chengjiang Lagerstätte, SW China) and the phylogenetic relationships within lobopodians.

New material of the lobopodian Luolishania longicruris has been recovered from the Lower Cambrian Chengjiang Lagerstätte, southwest China. The specimens throw new light on several morphological features of the species, including the paired antenniform outgrowths, eyes, head shield, setae and other cuticular projections, as well as the differentiated sclerites, appendages, claws, and lobopod interspaces. L. longicruris shows well developed tagmosis: a distinct head and a trunk divided into two sections. The new data allow a revised comparison with other lobopodians. Miraluolishania haikouensis Liu et al., 2004 is considered to be a junior synonym of L. longicruris Hou and Chen, 1989. Evidence from gut filling and specialized morphological characters indicates that L. longicruris may have had a filter feeding lifestyle. A new cladistic analysis suggests that fossil lobopodians are paraphyletic or even polyphyletic and L. longicruris may be an important representative of the stem lineage leading to arthropods.

Sensory structures of Archaeostraca (Phyllocaridida, Crustacea).

The carapace of some Archaeostraca exhibits two kinds of structures that are best interpreted as corresponding to sensory organs. Dorsal ones are located either along the dorsal margin of the valves of the carapace, or on the median dorsal plate. Anterolateral ones are located in the anterior region of both valves. Both structures are respectively homologous of the anterior and posterior sensory organs known from extant Leptostraca and other Crustacea. These structures are described in adult Archaeostraca from the Ordovician to the Carboniferous. It is expected that they could have baroreceptor, mechanoreceptor, and/or chemoreceptor functions in some cases, and a function in osmotic regulation in others.

An open study of the effectiveness of Internet treatment for panic disorder delivered in a psychiatric setting.

Panic disorder with or without agoraphobia (PD/A) is common and can be treated effectively with selective serotonin reuptake inhibitor (SSRI) medication or cognitive-behaviour therapy (CBT). However, the lack of access to CBT services has motivated the development of self-help approaches requiring less therapist contact. A novel treatment modality in this field, showing efficacy in several randomized trials but until now not evaluated within the context of regular psychiatric care, is Internet-based treatment. The aim of the present study was to evaluate the effectiveness of Internet-based CBT for patients in a psychiatric setting. Twenty consecutively referred patients with PD were included in the study. A structured clinical interview with a psychiatrist was conducted for inclusion, as well as at post-treatment and at the 6-month follow-up. The treatment consisted of a 10-week CBT-based self-help programme, including minimal therapist support by e-mail. At post-treatment, 94% of patients no longer met DSM-IV criteria for PD (82% at 6-month follow-up). The within-group effect sizes (for the main outcome PDSS; Panic Disorder Severity Scale) were Cohen's d=2.5 (pre- to post-treatment) and 2.8 (pre-treatment to follow-up), respectively. The proportion of responders on the PDSS was 75% at post-treatment and 70% at 6-month follow-up. The results supports earlier efficacy data on Internet-based CBT for PD and indicates that it is effective also within a regular psychiatric setting. However, a larger randomized controlled trial should be conducted, directly comparing Internet-based CBT with traditionally administered CBT within such a setting.