| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Johansson, Madeleine
(författare)
-
Longitudinellt perspektiv på symtomatisk remission vid schizofreni
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objective: The overall aim of this thesis was to investigate the remission criteria according to the Remisson in Schizophrenia Working Group (RWSG), mainly from a longitudinal perspective.Paper I showed that all remission symptoms in the RSWG criteria, affected the remission status in the cross-sectional setting. In the longitudinal setting, the symptoms Delusions and Hallucinatory behavior contributed mostly to the fluctuation between remission and non-remission, while negative symptoms were more prominent in the group that never reached remission. Finally, the sustainability of remission was significantly longer when only minimal symptom intensity occurred, compared with mild.Paper II showed that the cognitive areas associated with long-term remission pattern were executive functioning, working memory and verbal functioning, where significant better results were shown in the group of stable remission with only minimal symptoms compared to the group never reaching remission. Verbal functioning was the only cognitive area that could predict long-term remission pattern, as a better result increased the probability of being in long-term remission.Paper III focused on the patient’s perspective and examined the relationship between subjective quality of life (SQoL) and remission. The paper showed significant associations between a better SQoL, self-assessed with Short Form Health Survey-36, and both cross-sectional remission and long-term. A significant better SQoL was present regardless of being in stable remission over time or if remission was reached during the study period.Conclusions: The thesis support that the RSWG criteria for remission is a valuable concept, also from a longitudinal perspective. Taken together, the results emphasize the heterogeneity of schizophrenia, where different groups within the disorder show different clinical characteristics. This thesis highlights the importance of regular assessments of broad clinical status, to support a higher frequency and sustainability of remission.
|
|
| 5. |
- Pardiñas, Antonio F., et al.
(författare)
-
Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
- 2022
-
Ingår i: JAMA psychiatry. - Chicago, IL, United States : American Medical Association. - 2168-6238 .- 2168-622X. ; 79:3, s. 260-269
-
Tidskriftsartikel (refereegranskat)abstract
- Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts.Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples.Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]).Main Outcomes and Measures GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition.Results The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04).Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance.
|
|
| 6. |
- Smart, Sophie E., et al.
(författare)
-
Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium
- 2022
-
Ingår i: Schizophrenia Research. - : Elsevier. - 0920-9964 .- 1573-2509. ; 250
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionOur aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.MethodsWe combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction.ResultsOur sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %).ImplicationsOur findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.
|
|
