| 11. |
|
|
| 12. |
|
|
| 13. |
- Koppelman, SJ, et al.
(författare)
-
Allergenicity attributes of different peanut market types
- 2016
-
Ingår i: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. - : Elsevier BV. - 1873-6351. ; 91, s. 82-90
-
Tidskriftsartikel (refereegranskat)
|
|
| 14. |
|
|
| 15. |
- Lahteenvuo, M, et al.
(författare)
-
Effectiveness of antipsychotics in schizophrenia with comorbid substance use disorder
- 2021
-
Ingår i: EUROPEAN PSYCHIATRY. - : Royal College of Psychiatrists. - 0924-9338 .- 1778-3585. ; 64, s. S161-S161
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Schizophrenia is highly comorbid with substance use disorders (SUD), which may negatively impact the course of illness. However, large studies exploring the best lines of treatment for this combination are lacking.ObjectivesWe investigated what are the most effective antipsychotics for patients with schizophrenia in preventing the development of substance use disorders and preventing hospitalizations in patients already having substance use disorder.MethodsWe used two independent national cohort registries including all patient with schizophrenia aged under 46 years. Participants were followed during 22 (1996–2017, Finland) and 11 years (2006–2016, Sweden). We studied risk of rehospitalization, and risk of developing an SUD when using vs. not using antipsychotics, using Cox proportional hazards regression analysis models.Results45,476 patients with schizophrenia were identified (30,860 in Finland; 14,616 in Sweden). For patients without SUD, clozapine and antipsychotic polytherapy were associated with the lowest risks of developing SUD in both countries. For patients with co-existing SUD, the risk of hospitalization was the lowest during clozapine, polytherapy and long-acting injectable use.ConclusionsIn patients with schizophrenia and comorbid SUD, antipsychotic medications were effective in preventing relapses. In those without an SUD, antipsychotic use was associated with a markedly reduced risk of developing an initial SUD. Clozapine and long-acting injectables should be considered treatments of choice in patients with schizophrenia and SUD, or at risk of developing co-morbid SUD.DisclosureML: Genomi Solutions Ltd, DNE Ltd, Sunovion, Orion Pharma, Janssen-Cilag, Finnish Medical Foundation, Emil Aaltonen Foundation. HT, EMR, AT: Eli Lilly, Janssen–Cilag. JT: Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka.
|
|
| 16. |
- Lahteenvuo, M, et al.
(författare)
-
Morbidity and mortality in schizophrenia with comorbid substance use disorders in Finland and Sweden
- 2021
-
Ingår i: EUROPEAN PSYCHIATRY. - : Royal College of Psychiatrists. - 0924-9338 .- 1778-3585. ; 64, s. S237-S238
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Schizophrenia is highly comorbid with substance use disorders (SUD) but large epidemiological cohorts exploring the prevalence and prognostic significance of SUD are lacking.ObjectivesTo investigate the prevalence of SUD in patients with schizophrenia in Finland and Sweden, and the effect of these co-occurring disorders on risks of psychiatric hospitalization and mortality.Methods45,476 individuals with schizophrenia from two independent national cohort studies, aged <46 years at cohort entry, were followed during 22 (1996-2017, Finland) and 11 years (2006-2016, Sweden). We first assessed SUD prevalence (excluding smoking). Then we performed Cox regression on risk of psychiatric hospitalization and mortality in patients with schizohrenia and SUD compared with those without SUD.ResultsThe prevalence of SUD in specialized healthcare ranged from 26% (Finland) to 31% (Sweden). Multiple drug use and alcohol use disorders were the most prevalent SUD, followed by cannabis use disorders. Any SUD comorbidity, and particularly multiple drug use and alcohol use, were associated with 50% to 100% increases in hospitalization and mortality compared to individuals without SUD. Elevated mortality risks were observed especially for deaths due to suicide and other external causes. All results were similar across countries.ConclusionsCo-occurring SUD, and particularly alcohol and multiple drug use, are associated with high rates of hospitalization and mortality in patients with schizophrenia. Preventive interventions should prioritize detection and tailored treatments for these co-morbidities, which often remain underdiagnosed and untreated.Conflict of interestML: Genomi Solutions Ltd, Nursie Health Ltd, Sunovion, Orion Pharma, Janssen-Cilag, Finnish Medical Foundation, Emil Aaltonen Foundation. HT, EMR, AT: Eli Lilly, Janssen–Cilag. JT: Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka.
|
|
| 17. |
- Okhuijsen-Pfeifer, C, et al.
(författare)
-
Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders
- 2022
-
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 145-
-
Tidskriftsartikel (refereegranskat)abstract
- Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10−3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10−4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10−3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10−7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.
|
|
| 18. |
- Olislagers, M., et al.
(författare)
-
Comprehensive analyses of RNA-seq and genome-wide data point to enrichment of neuronal cell type subsets in neuropsychiatric disorders
- 2022
-
Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 27, s. 947-955
-
Tidskriftsartikel (refereegranskat)abstract
- Neurological and psychiatric disorders, including substance use disorders, share a range of symptoms, which could be the result of shared genetic background. Many genetic loci have been identified for these disorders using genome-wide association studies, but conclusive evidence about cell types wherein these loci are active is lacking. We aimed to uncover implicated brain cell types in neuropsychiatric traits and to assess consistency in results across RNA datasets and methods. We therefore comprehensively employed cell type enrichment methods by integrating single-cell transcriptomic data from mouse brain regions with an unprecedented dataset of 42 human genome-wide association study results of neuropsychiatric, substance use and behavioral/quantitative brain-related traits (n = 12,544,007 individuals). Single-cell transcriptomic datasets from the Karolinska Institute and 10x Genomics were used. Cell type enrichment was determined using Linkage Disequilibrium Score Regression, Multi-marker Analysis of GenoMic Annotation, and Data-driven Expression Prioritized Integration for Complex Traits. We found the largest degree of consistency across methods for implication of pyramidal cells in schizophrenia and cognitive performance. For other phenotypes, such as bipolar disorder, two methods implicated the same cell types, i.e., medium spiny neurons and pyramidal cells. For autism spectrum disorders and anorexia nervosa, no consistency in implicated cell types was observed across methods. We found no evidence for astrocytes being consistently implicated in neuropsychiatric traits. In conclusion, we provide comprehensive evidence for a subset of neuronal cell types being consistently implicated in several, but not all psychiatric disorders, while non-neuronal cell types seem less implicated. © 2021, The Author(s).
|
|
| 19. |
|
|
| 20. |
|
|
