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- Herrera-Rivero, Marisol, et al.
(författare)
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Exploring the genetics of lithium response in bipolar disorders.
- 2023
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Ingår i: Research square.
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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.
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- Natchimuthu, Sivakiruthika
(författare)
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Freshwater methane and carbon dioxide fluxes : Spatio-temporal variability and an integrated assessment of lake and stream emissions in a catchment
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Freshwater bodies such as lakes and streams release the greenhouse gases methane (CH4) and carbon dioxide (CO2) into the atmosphere. Global freshwater CH4 and CO2 emissions have been estimated to be of a similar magnitude to the global land or ocean carbon sink, and are thus significant components of global carbon budgets. However, the data supporting global estimates frequently lacks information regarding spatial and temporal variability and are thus highly inaccurate. In this thesis, detailed studies of the spatio-temporal variability of CH4 and CO2 fluxes were conducted in the open water areas of lakes and streams within a whole catchment in Sweden. One aim was also to evaluate the importance of spatio-temporal variability in lake and stream fluxes when making whole catchment aquatic or large scale assessments. Apart from the expected large spatio-temporal variability in lake fluxes, interactions between spatial and temporal variability in CH4 fluxes were found. Shallow lakes and shallow areas of lakes were observed to emit more CH4 as compared to their deeper counterparts. This spatial variability interacted with the temporal variability driven by an exponential temperature response of the fluxes, which meant that shallow waters were more sensitive to warming than deeper ones. Such interactions may be important for climate feedbacks. Surface water CO2 in lakes showed significant spatio-temporal variability and, when considering variability in both space and time, CO2 fluxes were largely controlled by concentrations, rather than gas transfer velocities. Stream fluxes were also highly variable in space and time and in particular, stream CH4 fluxes were surprisingly large and more variable than CO2 fluxes. Fluxes were large from stream areas with steep slopes and periods of high discharge which occupied a small fraction of the total stream area and the total measurement period, respectively, and a failure to account for these spatially distinct or episodic high fluxes could lead to underestimates. The total aquatic fluxes from the whole catchment were estimated by combining the measurements in open waters of lakes and streams. Using our data, recommendations on improved study designs for representative measurements in lakes and streams were provided for future studies. Thus, this thesis presents findings relating to flux regulation in lakes and streams, and urges forthcoming studies to better consider spatio-temporal variability so as to achieve unbiased large-scale estimates.
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