| 1. |
- Herrera-Rivero, Marisol, et al.
(författare)
-
Exploring the genetics of lithium response in bipolar disorders.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
|
|
| 2. |
- Herrera-Rivero, Marisol, et al.
(författare)
-
Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
|
|
| 3. |
- Kelsoe, John, et al.
(författare)
-
Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
|
|
| 4. |
- Bernal, Ximena E., et al.
(författare)
-
Empowering Latina scientists
- 2019
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 5. |
- Hagström, Peter, 1967-
(författare)
-
Biomass Potential for Heat, Electricity and Vehicle Fuel in Sweden
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main objective of this thesis was to determine how far a biomass quantity, equal to the potential produced within the Swedish borders, could cover the present energy needs inSwedenwith respect to economic and ecological circumstances. Three scenarios were studied where the available biomass was converted to heat, electricity and vehicle fuel. Three different amounts of biomass supply were studied for each scenario: 1) potential biomass amounts derived from forestry, non-forest land, forest industry and community; 2) the same amounts as in Case 1, plus the potential biomass amounts derived from agriculture; 3) the same amounts as in Case 1, plus 50% of the potential pulpwood quantity.For evaluating the economic and ecological circumstances of using biomass in the Swedish energy system, the scenarios were complemented with energy, cost and emergy analysis.The scenarios indicated that it may be possible to produce 170.2 PJ (47.3 TWh) per year of electricity from the biomass amounts in Case 2. From the same amount of biomass, the maximum annual production of hydrogen was 241.5 PJ (67.1 TWh) per year or 197.2 PJ (54.8 TWh) per year of methanol.The energy analysis showed that the ratio of energy output to energy input for large-scale applications ranged from 1.9 at electric power generation by gasification of straw to 40 at district heating generation by combustion of recovered wood. The cost of electricity at gasification ranged from 7.95 to 22.58 €/GJ. The cost of vehicle work generated by using hydrogen produced from forestry biomass in novel fuel cells was economically competitive compared to today’s propulsion systems. However, the cost of vehicle work generated by using methanol produced from forestry biomass in combustion engines was rather higher compared to use of petrol in petrol engines.The emergy analysis indicated that the only biomass assortment studied with a larger emergy flow from the local environment, in relation to the emergy flow invested from society after conversion, was fuel wood from non-forest land. However, even use of this biomass assortment for production of heat, electricity or vehicle fuels had smaller yields of emergy output in relation to emergy invested from society compared to alternative conversion processes; thus, the net contribution of emergy generated to the economy was smaller compared to these alternative conversion processes.
|
|
| 6. |
- Lane, Paul, 1957-, et al.
(författare)
-
Introducing African archaeology
- 2013
-
Ingår i: <em>The Oxford</em> <em>Handbook of African Archaeology</em>. - Oxford : Oxford University Press. ; , s. 3-11
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 7. |
|
|
| 8. |
|
|
