A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders.

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.

DNA methylation of FKBP5 and response to exposure-based psychological therapy.

Differential DNA methylation of the hypothalamic-pituitary-adrenal axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences and may play a role in how well people respond to psychological treatments. Participants (n = 111) received exposure-based cognitive behavioural therapy (CBT) for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (ß = -4.26, p = 3.90 × 10-4 ), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p = .045) but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences.

Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders.

OBJECTIVES: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. METHODS: Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. RESULTS: Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. CONCLUSIONS: We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.

Internal bacterial colonization of implants: association with peri-implant bone loss.

OBJECTIVES: The aim of the present longitudinal study was to investigate bacterial colonization of the internal implant cavity and to evaluate a possible association with peri-implant bone loss. METHODS: A total of 264 paper point samples were harvested from the intra-implant cavity of 66 implants in 26 patients immediately following implant insertion and after 3, 4, and 12 months. Samples were evaluated for Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia as well as total bacterial counts by real-time PCR. Bone loss was evaluated on standardized radiographs up to 25 months after implant insertion. For the statistical analysis of the data, mixed effects models were fitted. RESULTS: There was an increase in the frequency of detection as well as in the mean counts of the selected bacteria over time. The evaluation of the target bacteria revealed a significant association of Pr. intermedia at 4 and 12 months with peri-implant bone loss at 25 months (4 months: P = 0.009; 12 months: P = 0.021). CONCLUSIONS: The present study could demonstrate a progressive colonization by periodontopathogenic bacteria in the internal cavities of two-piece implants. The results suggest that internal colonization with Pr. intermedia was associated with peri-implant bone loss.

Dental phobia is no contraindication for oral implant therapy.

OBJECTIVES: Dental phobia is a psychological disease and a possible contraindication for implant therapy. The study aimed to show that implant therapy in dental-phobic patients (DP, test group) after adequate psychological and dental pretreatment (PDPT) is successfully possible and results in a similar implant prognosis as in nonfearful patients (NF, control group). METHOD AND MATERIALS: 15 DP with PDPT and 15 NF were treated with dental implants and were re-evaluated 2 to 4 years after denture-mounting regarding: alteration of dental anxiety (Hierarchical Anxiety Questionnaire [HAQ], Visual Analog Scale [VAS]), patient satisfaction and compliance, implant success, and peri-implant health. Statistical tests of non-inferiority DP versus NF were performed with Hodges-Lehmann estimators and respective one-sided 97.5% confidence intervals of Moses, and pairwise testings with Mann-Whitney test. RESULTS: The DP test group rated its anxiety significantly lower at follow- up than at baseline (PHAQ < .001). However, at follow-up, anxiety was still higher in DP than in NF (PHAQ = .046; PVAS < .001). Implant success at follow-up was 100%. Oral health was equally good in DP and NF patients. At follow-up, all patients were satisfied with implant therapy, but compliance was better for NF (100%) than for DP (73% dental checkup; 67% dental hygienist). CONCLUSION: Implant therapy can be successfully performed in DP patients with PDPT as phobia is not negatively influenced by the invasive implant therapy. However, motivation for professional maintenance programs remains challenging.

Mental retrieval of treatment context in dental phobia.

BACKGROUND: The effect of mental retrieval of an exposure session was investigated during a follow-up examination in dental phobia patients. METHOD: The exposure session took place at the psychology unit and the follow-up a week later at the dental clinic prior to dental treatment while patients were seated in the dental chair. During exposure, individuals with dental phobia (N = 72) were shown a video of a dental appointment, after which they were instructed to imagine themselves receiving dental treatment. During follow-up half of the participants received instructions to mentally retrieve the exposure session and the other half were asked to recall everyday activities. Before and after exposure treatment, and after mental retrieval, participants were shown three dental instruments while heart rate (HR) and avoidance and subjective units of discomfort (SUD) were recorded. RESULTS: Questionnaires of phobic anxiety administered before and after treatment indicated significant improvement. Mental retrieval of treatment was moderately superior to the control condition with regard to avoidance. Over 80% of patients underwent the subsequent dental treatment session. Those not adhering showed initially more dysfunctional cognitions and more desire for control. CONCLUSION: There is some evidence that retrieval of treatment context may have a moderately beneficial effect on avoidance.

Impact of anxiety parameters on prospective and experienced pain intensity in implant surgery.

PURPOSE: To investigate the relationship between anxiety and pain perception in the context of implant surgery and to examine the impact of factors such as gender and surgery duration on anxiety and pain levels. METHODS: One hundred twenty-one patients undergoing implant surgery evaluated their anxiety and pain levels by completing a set of 2 questionnaires at different points in time. RESULTS: Both anxiety and pain levels were highest on the day of surgery and showed a significant decrease when evaluated retrospectively (P < 0.01; P < 0.05). Correlations were found between preoperative anxiety and expected pain levels (r = 0.19), pain peak and duration of pain (r = 0.79), and a nearly significant correlation between preoperative anxiety and duration of pain (r = 0.18). Women showed significantly higher levels of preoperative anxiety (P < 0.05) and expected pain (P < 0.05) than men. CONCLUSION: The results confirm a strong negative impact of increased preoperative anxiety levels on pain perception and the recovery process. Therefore, future research should focus on individual patient's sources of dental anxiety to reduce its negative consequences.

Vinylsiloxanether: a new impression material. Clinical study of implant impressions with vinylsiloxanether versus polyether materials.

AIM: The performance of three elastomeric materials for the open monophase implant impressions technique was tested under the following clinical conditions: polyether (IM) and vinylsiloxanether without (ID) and with additional simultaneous splinting of the implant impression copings with a higher shore hardness A-silicone (IDF). MATERIALS AND METHODS: The three test groups, IM, ID, and IDF, were randomly allocated 10 test subjects with three to five implants each. The impressions were analyzed regarding the subjective clinical assessments with 11-point rating scales by the dentist, the patient, and the dental technician, as well as to the comparison of these assessments with the objectified clinical fit of the manufactured crowns based on standard clinical evaluation criteria. The three groups were statistically analyzed on the basis of the hypothesis of non-inferiority of ID versus IM and IDF versus IM (alpha < 0.05). RESULTS: The results of the study showed the objective clinical fit of the dental prostheses made using ID being comparable to the results obtained with IM. Compared with ID and IM, the precision of fit attained with IDF was reduced, although the subjective dentist assessments of IDF were in parts significantly better than those of IM and ID (p = .015). A statistically significant superiority of ID in comparison with IM could be determined with regard to the subjective ratings of the taste by the test subject (p < .01), of the handling (p < .001) and of the precision details of impression (p = .012) by the dentist, and of removing the plaster model from the mold by the dental technician (p = .017). CONCLUSIONS: The overall results of the vinylsiloxanether material in terms of the patients', dentists', and dental technicians' assessments proved to be equivalent or superior to those of the polyether material. The IDF technique cannot be recommended for this application.

Effect of platform switching on peri-implant bone levels: a randomized clinical trial.

OBJECTIVE: The concept of platform switching has been introduced to implant dentistry based on observations of reduced peri-implant bone loss. However, randomized clinical trials are still lacking. This study aimed to test the hypothesis that platform switching has a positive impact on crestal bone-level changes. MATERIAL AND METHODS: Two implants with diameters of 4 mm were inserted epicrestally into one side of the posterior mandibles of 25 subjects. After 3 months of submerged healing, the reentry surgery was performed. On the randomly placed test implant, an abutment 3.3 mm in diameter was mounted, resulting in a horizontal circular step of 0.35 mm (platform switching). The control implant was straight, with an abutment 4 mm in diameter. Single-tooth crowns were cemented provisionally. All patients were monitored at short intervals over the course of 1 year. Standardized radiographs and microbiological samples from the implants' inner spaces were obtained at baseline (implant surgery), and after 3, 4, and 12 months. RESULTS: After 1 year, the mean radiographic vertical bone loss at the test implants was 0.53±0.35 mm and at the control implants, it was 0.58±0.55 mm. The mean intraindividual difference was 0.05±0.56 mm, which is significantly <0.35 mm (P=0.0093, post hoc power 79.9%). The crestal bone-level changes depended on time (P<0.001), but not on platform switching (P=0.4). The implants' internal spaces were contaminated by bacteria, with no significant differences in the total counts between the test and the control at any time point (P=0.98). CONCLUSIONS: The present randomized clinical trial could not confirm the hypothesis of a reduced peri-implant bone loss at implants restored according to the concept of platform switching.

Open or submerged healing of implants with platform switching: a randomized, controlled clinical trial.

AIM: The temporal pattern of bone-level alterations in conventionally restored implants is dependent upon healing mode (open or submerged). This study examined the influence of healing on marginal bone levels at implants with a medium-rough surface including the implant collar and a clearance-fit implant-abutment connection restored according to a platform-switching concept. MATERIAL AND METHODS: Two implants were placed in the posterior mandible of 21 test subjects, randomly assigned to open (OH) or submerged (SH) healing. Standardized radiographs were obtained after implant surgery, before re-entry, after crown mounting, 1 and 2 years after implant surgery, and evaluated for implant-bone-level alterations (ΔIBL). Bacterial samples of the implants' inner cavities were analysed by cultivation. STATISTICS: Brunner-Langer Model, equivalence testings by Wilcoxon's (equivalence range ±0.4mm). RESULTS: After 2 years, ΔIBL were -0.47±0.46mm (OH) and -0.54±0.38mm (SH). At the 1-year follow-up, all implants were contaminated with bacteria. ΔIBL (p<0.001) and the amount of bacterial contamination (p<0.001) significantly depended on time, but not on healing mode. ΔIBL of OH and SH were equivalent at all time points (all p0.044). CONCLUSIONS: Platform-switched implants showed very limited peri-implant bone-level alterations. The healing-mode neither affected the total amount nor the temporal patterns of ΔIBL. Thus, the results for the tested implants with a non-rigid implant-abutment connection were similar to results reported previously for implants with a rigid implant-abutment connection.

Attention focusing versus distraction during exposure in dental phobia.

A survey of the discrepant findings regarding the effects of attention focusing and distraction on exposure suggested that subjective measures of anxiety and avoidance respond better to the latter condition, and heart rate (HR) reaction responds to the former. To test this hypothesis, 63 dental phobics were recruited who had not visited a dentist for a mean of 6.6 (1.5-25) years. Participants received a 1-h exposure session with either attention focusing or distraction. Subjective anxiety and HR to phobia-related pictures were assessed before and after the treatment session and again after 1 week. Avoidance was recorded in terms of adherence to the dental treatment schedule in the following 6 months. Contrary to expectation, state anxiety showed a greater decrease in the attention focusing than the distraction condition after 1 week. Both treatment conditions were similarly effective with regard to HR and avoidance. HR habituated in both groups after exposure and 73% of followed-up patients adhered to the dental treatment schedule. Comparison of the present with previous results suggests that the differences between attentional conditions tend to be more pronounced during shorter exposure sessions than were employed in the present study.

Tactile sensibility of single-tooth implants and natural teeth.

AIM: The purpose of this randomized split-mouth clinical trial was to determine the active tactile sensibility between single-tooth implants and opposing natural teeth and to compare it with the tactile sensibility of pairs of natural teeth on the contralateral side in the same mouth (intraindividual comparison). MATERIAL AND METHODS: The hypothesis was that the active tactile sensibilities of the implant side and control side are equivalent. Sixty two subjects (n=36 from Bonn, n=26 from Bern) with single-tooth implants (22 anterior and 40 posterior dental implants) were asked to bite on narrow copper foil strips varying in thickness (5-200 microm) and to decide whether or not they were able to identify a foreign body between their teeth. Active tactile sensibility was defined as the 50% threshold of correct answers estimated by means of the Weibull distribution. RESULTS: The results obtained for the interocclusal perception sensibility differed between subjects far more than they differed between natural teeth and implants in the same individual [implant/natural tooth: 16.7+/-11.3 microm (0.6-53.1 microm); natural tooth/natural tooth: 14.3+/-10.6 microm (0.5-68.2 microm)]. The intraindividual differences only amounted to a mean value of 2.4+/-9.4 microm (-15.1 to 27.5 microm). The result of our statistical calculations showed that the active tactile sensibility of single-tooth implants, both in the anterior and posterior region of the mouth, in combination with a natural opposing tooth is similar to that of pairs of opposing natural teeth (double t-test, equivalence margin: +/-8 microm, P<0.001, power >80%). Hence, the implants could be integrated in the stomatognathic control circuit.

Clinical outcome of a short-term psychotherapeutic intervention for the treatment of dental phobia.

OBJECTIVE: Anxiety before receiving dental treatment is widespread. The aim of this investigation was to evaluate the effect of a brief psychologic treatment on adherence to the dental treatment regimen in patients with dental phobia. METHOD AND MATERIALS: Dental phobic patients (n = 160) received 3 sessions of cognitive behavioral therapy that consisted of stress management training and exposure to phobic stimuli. The outcome was determined in terms of 3 subsequent dental visits. RESULTS: Participating patients had not visited a dental clinician for an average of 6 years. Comparison of patients who completed the psychologic treatment with those who dropped out showed that 68% of the former but also 52% of the latter adhered to the subsequent dental treatment regimen. The number of psychologic treatment sessions correlated significantly and positively with anxiety level before treatment. CONCLUSION: Short-term psychologic therapy of 3 sessions results in a success rate of 70% to adherence to dental treatment among dental phobic patients. Duration of avoidance of anxiety before treatment was not related to success in completing the trial. Nevertheless, the more intense the patient's phobia, the more psychotherapeutic sessions were necessary.