| 1. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 2. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 3. |
- Cooper, Lyndon F., et al.
(författare)
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Immediate Provisionalization of Dental Implants Placed in Healed Alveolar Ridges and Extraction Sockets : A 5-year Prospective Evaluation
- 2014
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Ingår i: International Journal of Oral & Maxillofacial Implants. - : Quintessence. - 0882-2786 .- 1942-4434. ; 29:3, s. 709-717
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This 5-year prospective multicenter study compared implant survival and success, peri-implant health and soft tissue responses, crestal bone level stability, and complication rates following immediate loading of single OsseoSpeed implants placed in anterior maxillary healed ridges or extraction sockets. Materials and Methods: Individuals requiring anterior tooth replacement with single implants were treated and immediately provisionalized. Definitive all-ceramic crowns were placed at 12 weeks. Implant survival, bone levels, soft tissue levels, and peri-implant health were monitored for 5 years. Results: One hundred thirteen patients received implants in fresh sockets (55) and healed ridges (58). After 5 years, 45 and 49 patients remained for evaluation, respectively. During the first year, three implants failed in the extraction socket group (94.6% survival) and one implant failed in the healed ridge group (98.3% survival); this difference was not significant. No further implant failures were recorded. After 5 years, the interproximal crestal bone levels were located a mean of 0.43 +/- 0.63 mm and 0.38 +/- 0.62 mm from the reference points of implants in sockets and healed ridges (not a significant difference). In both groups, papillae increased over time and peri-implant mucosal zenith positions were stable from the time of definitive crown placement in sockets and healed ridges. Compared to flap surgery for implants in healed ridges, flapless surgery resulted in increased peri-implant mucosal tissue dimension (average, 0.78 +/- 1.34 mm vs 0.19 +/- 0.79 mm). Conclusion: After 5 years, the bone and soft tissue parameters that characterize implant success and contribute to dental implant esthetics were similar following the immediate provisionalization of implants in sockets and healed ridges. The overall tissue responses and reported implant survival support the immediate provisionalization of dental implants in situations involving healed ridges and, under ideal circumstances, extraction sockets.
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| 4. |
- De Bruyn, Hugo, et al.
(författare)
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Three-years clinical outcome of immediate provisionalization of single Osseospeed™ implants in extraction sockets and healed ridges
- 2013
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Ingår i: Clinical Oral Implants Research. - : John Wiley & Sons. - 0905-7161 .- 1600-0501. ; 24:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Aim The purpose of this prospective multicenter clinical study was to compare 3 years implant survival, bone and soft tissue changes following immediate loading using single Osseospeed™ implants (Astra Tech AB, Mölndal, Sweden) installed in healed ridges or extraction sockets. Material and methods Implants were provisionally restored the day of surgery using cemented acrylic crowns out of full occlusion. The provisional crowns were replaced after 12 weeks by full-ceramic crowns. Implant survival, bone levels, soft tissue levels and peri-implant health were monitored up to 3 years. Results 55 patients (22 men, 33 women; mean age 45) had the implant installed in extraction sockets and 58 patients (25 men, 33 women; mean age 42) received conventional implant treatment in healed ridges. Three implants failed in the extraction group and one implant failed in the healed group, all failures occurred before the final crown placement. No further losses occurred during 3 years, giving a statistically comparable survival rate of 94.6% and 98.3%, respectively. The total bone loss after 3 years, compared to implant placement was 0.4 mm (SD 1.5) in healed sites, whilst the immediate sites showed a bone gain of 1.6 mm (SD 2.4) due to bone fill in the alveolus. Papillae retracted with 0.3 and 0.0 mm in the period of provisionalization, but grew back after final crown was placed with 0.3 and 0.5 mm in extraction and healed sites respectively after 3 years. Plaque and inflammation scores were very low throughout the study time, irrespective of treatment modality. Conclusions Immediate implants restored at the day of surgery show comparable risk for implant failure, bone loss and midfacial soft tissue recession compared to conventionally installed implants. The 3-years results suggest both hard and soft tissue stability.
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| 5. |
- Hämmerle, Christoph H.F., et al.
(författare)
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Submerged and transmucosal healing yield the same clinical outcomes with two-piece implants in the anterior maxilla and mandible: Interim 1-year results of a randomized, controlled clinical trial
- 2012
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Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 23:2, s. 211-219
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To test whether or not transmucosal healing at two-piece implants is as successful as submerged placement regarding crestal bone levels and patient satisfaction. Material and methods: Adults requiring implants in the anterior maxilla or mandible in regions 21-25, 11-15, 31-35 or 41-45 (WHO) were recruited for this randomized, controlled multi-center clinical trial of a 5-year duration. Randomization was performed at implantation allowing for either submerged or transmucosal healing. Final reconstructions were seated 6 months after implantation. Radiographic interproximal crestal bone levels and peri-implant soft tissue parameters were measured at implant placement (IP) (baseline), 6 and 12 months. Patient satisfaction was assessed by a questionnaire. A two-sided t-test (80% power, significance level α=0.05) was performed on bone-level changes at 6 and 12 months. Results: One hundred and twenty-seven subjects were included in the 12-month analysis (submerged [S]: 52.5%, transmucosal [TM]: 47.2%). From IP to 6 months, the change in the crestal bone level was -0.32mm (P<0.001) for the S group and -0.29mm (P<0.001) for the TM group. From IP to 12 months, bone-level changes were statistically significant in both groups (S -0.47 mm, P<0.001; TM -0.48mm, P<0.001). The mean differences of change in the bone levels between the two groups were not statistically significant at either time point, indicating the equivalence of both procedures. For both groups, very good results were obtained for soft tissue parameters and for patient satisfaction. Conclusions: Transmucosal healing of two-piece implants is as successful as the submerged healing mode with respect to tissue integration and patient satisfaction within the first 12 months after IP. © 2011 John Wiley & Sons A/S.
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| 6. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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