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- Pisanu, Claudia, et al.
(författare)
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Recent trends on the role of epigenomics, metabolomics and noncoding RNAs in rationalizing mood stabilizing treatment
- 2018
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Ingår i: Pharmacogenomics (London). - : Future Medicine Ltd. - 1462-2416 .- 1744-8042. ; 19:2, s. 129-143
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Forskningsöversikt (refereegranskat)abstract
- Mood stabilizers are the cornerstone in treatment of mood disorders, but their use is characterized by high interindividual variability. This feature has stimulated intensive research to identify predictive biomarkers of response and disentangle the molecular bases of their clinical efficacy. Nevertheless, findings from studies conducted so far have only explained a small proportion of the observed variability, suggesting that factors other than DNA variants could be involved. A growing body of research has been focusing on the role of epigenetics and metabolomics in response to mood stabilizers, especially lithium salts. Studies from these approaches have provided new insights into the molecular networks and processes involved in the mechanism of action of mood stabilizers, promoting a systems-level multiomics synergy. In this article, we reviewed the literature investigating the involvement of epigenetic mechanisms, noncoding RNAs and metabolomic modifications in bipolar disorder and the mechanism of action and clinical efficacy of mood stabilizers.
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| 2. |
- Pisanu, Claudia, et al.
(författare)
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The Role of Pharmacogenomics in Bipolar Disorder : Moving Towards Precision Medicine
- 2018
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Ingår i: Molecular Diagnosis & Therapy. - : Springer Science and Business Media LLC. - 1177-1062 .- 1179-2000. ; 22:4, s. 409-420
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Forskningsöversikt (refereegranskat)abstract
- Bipolar disorder (BD) is a common and disabling psychiatric condition with a severe socioeconomic impact. BD is treated with mood stabilizers, among which lithium represents the first-line treatment. Lithium alone or in combination is effective in 60% of chronically treated patients, but response remains heterogenous and a large number of patients require a change in therapy after several weeks or months. Many studies have so far tried to identify molecular and genetic markers that could help us to predict response to mood stabilizers or the risk for adverse drug reactions. Pharmacogenetic studies in BD have been for the most part focused on lithium, but the complexity and variability of the response phenotype, together with the unclear mechanism of action of lithium, limited the power of these studies to identify robust biomarkers. Recent pharmacogenomic studies on lithium response have provided promising findings, suggesting that the integration of genome-wide investigations with deep phenotyping, in silico analyses and machine learning could lead us closer to personalized treatments for BD. Nevertheless, to date none of the genes suggested by pharmacogenetic studies on mood stabilizers have been included in any of the genetic tests approved by the Food and Drug Administration (FDA) for drug efficacy. On the other hand, genetic information has been included in drug labels to test for the safety of carbamazepine and valproate. In this review, we will outline available studies investigating the pharmacogenetics and pharmacogenomics of lithium and other mood stabilizers, with a specific focus on the limitations of these studies and potential strategies to overcome them. We will also discuss FDA-approved pharmacogenetic tests for treatments commonly used in the management of BD.
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| 3. |
- Pisanu, Claudia, et al.
(författare)
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We are not Alone in Our Body : Insights into the Involvement of Microbiota in the Etiopathogenesis and Pharmacology of Mental Illness
- 2018
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Ingår i: Current drug metabolism. - : BENTHAM SCIENCE PUBL LTD. - 1389-2002 .- 1875-5453. ; 19:8, s. 688-694
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Forskningsöversikt (refereegranskat)abstract
- Background: The etiopathogenesis of psychiatric disorders is still not completely understood. Growing evidence supports the hypothesis that mental illness and related disturbances do not necessarily originate in the brain. Inflammation has been suggested to play a central role in psychiatric disorders and altered levels of peripheral cytokines have been reported in several studies. Recently, it has emerged that bacteria populating the human gut could modulate low-grade inflammation, as well as high-order brain functions, including mood and behavior. These bacteria constitute the microbiota, a large population comprising 40,000 bacterial species and 1,800 phila involved in key processes important to maintain body homeostasis. Method: In this review, we present and discuss studies exploring the role of dysbiosis and products of the gut-microbiota in the pathogenesis of psychiatric disorders, as well as their potential involvement in mediating the effect of antidepressants, mood stabilizers, and antipsychotics. Results: Although this field is still at its early stage of development, a growing number of studies suggest that an altered composition of the gut microbiota, together with translocation of bacterial products into the systemic circulation, might play a role in the pathogenesis of psychiatric disorders as well as in response to psychotropic medications. Conclusion: An altered composition and functioning of gut microbiota have been reported in psychiatric disorders, and recent findings suggest that gut bacteria could be involved in modulating the efficacy of psychotropic medications.
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| 4. |
- Skuladottir, Gudrun Valgerdur, et al.
(författare)
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Plasma stearoyl-CoA desaturase activity indices and bile acid concentrations after a low-fat meal : association with a genetic variant in the FTO gene
- 2018
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Ingår i: Diabetes, Metabolic Syndrome and Obesity. - 1178-7007 .- 1178-7007. ; 11, s. 611-618
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Dietary macronutrient composition, stearoyl-CoA desaturase (SCD) activity indices, and primary bile acid (BA) concentrations are among the factors that have been associated with lipid metabolism and contributed to obesity. We investigated the association between the polymorphic expression of the fat mass and obesity-associated (FTO) gene and its relationship with SCD activity indices and primary BA concentrations after a low-fat meal. Subjects and methods: Blood plasma samples were collected from 56 young (20-36 years) healthy subjects with different rs9939609 FTO genotypes. Fasting and post-meal (2 hours after a low-fat breakfast) blood samples were collected on the subsequent morning for the analysis of DNA methylation, SCD activity indices (product-to-precursor fatty acid ratios; 16:1n-7/16:0 and 18: 1n-9/18:0), and chenodeoxycholic acid (CDCA) and cholic acid (CA) concentrations. Expression of lipogenic genes was investigated post-meal to assess the relationship between the CDCA and CA concentrations and mRNA levels of lipogenic genes. Results: The FTO AA (obesity risk) genotype group (n = 18) had higher (P<0.05) post-meal SCD-16 activity index than the FTO TT (wild type) genotype group (n=26). In both the FTO TT (n=16) and AA (n=8) genotype groups, the post-meal concentrations of CDCA and CA were lower (P<0.05) compared with the fasted state. No difference in BA concentrations between the FTO TT and AA genotype groups in both meal states was observed. After adjusting for the body mass index, the highest 50% post-meal concentrations of CA were inversely (P=0.010) correlated with the level of mRNA SCD expression. Conclusion: FTO AA carriers may be at a higher risk for obesity through higher SCD activity in a low-fat diet environment. This effect may be partly pronounced by very low CA concentrations.
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