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- Kaltsouni, Elisavet, et al.
(författare)
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Selective progesterone receptor modulation and brain activity at rest in patients with premenstrual dysphoric disorder
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian hormones have been indicated to impact brain connectivity and mood. However, there is no consistent evidence on hormone-dependent functional connectivity and mental health. Alterations in resting state networks have been suggested as markers of affective disorders, but only preliminary evidence is provided on premenstrual dysphoric disorder, in which symptoms occur upon fluctuations of ovarian hormones. Recently, three-month low-dose selective progesterone receptor modulator (SPRM) administration has been associated with symptom relief and altered task-based brain reactivity during a reactive aggression condition. The present study sought to investigate the effect of this treatment on resting state functional connectivity (rs-FC) in patients with PMDD. Seed-based analyses were conducted, including including seeds from the classic resting state networks along with the functional cluster affected by SPRM treatment. Within previously identified networks related with emotional processing, rs-FC was compared between individuals with PMDD during the symptomatic luteal phase before randomization to treatment or placebo and during the end of the last treatment cycle. Seed-based rs-FC analyses yielded significant treatment by time effects on rs-FC between the left posterior superior temporal gyrus and the right insula cortex, between the posterior cerebellum and the left temporal pole, and between the right lateral visual network and left superior frontal gyrus. Visuo-frontal luteal phase connectivity decreased for the SPRM group and was positively correlated with changes in mood symptom severity in the placebo group. Cerebellar and temporal connectivity increased for the SPRM treatment group, while temporo-insular connectivity decreased and was positively correlated with cortisol levels. These findings indicate that SPRM treatment influenced rs-FC, which could be a relevant mechanism behind symptom alleviation.
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- Espregueira Themudo, Raquel, 1978-, et al.
(författare)
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Clinically unrecognized myocardial scars detected by MR are not associated with coronary artery disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: We have previously discovered an unexpected high prevalence of unrecognized myocardial infarction (UMI) scars by delayed-enhanced magnetic resonance imaging (DE-MRI) in the general elderly population. We now investigated if those UMIs were associated with coronary artery disease (CAD). Methods: Eighty-eight subjects from the PIVUS study (age 75-years) who had been investigated with DE-MRI (45 with UMI and 43 without DE-MRI-detected scars) underwent coronary computed tomography angiography (CTA) to assess Agatston calcium score and coronary artery stenosis. Of those, 65 also performed an exercise ECG test. Results: No differences were found between the subjects with UMI and the group without DE-MRI-detected scars regarding the number of coronary artery segments with significant stenosis, Agatston calcium score, or degree of ST-depression at the exercise test. Conclusion: DE-MRI-detected UMI scars do not have an increased prevalence of coronary artery stenosis or signs of myocardial ischemia at exercise test when compared to a control group. These findings indicate that UMI scars in general are not related to CAD.
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- van der Meer, Dennis, et al.
(författare)
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The role of liver fat in cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background & AimsObesity and associated morbidities, metabolic associated liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting the first genome-wide association study (GWAS) of these MRI-derived measures.MethodsWe ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 34,036 White European UK Biobank participants (mean age of 64.5 years, 51.5% female).ResultsThrough multivariate analysis, we discovered 108 loci with distributed effects across the body composition measures and 256 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h2=.25 vs. .16, p=1.4×10−6). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (rg=.48, p=1.6×10−22).ConclusionsThese findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.
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- Kaltsouni, Elisavet, et al.
(författare)
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White matter integrity upon progesterone antagonism in individuals with premenstrual dysphoric disorder: a randomized placebo-controlled diffusion tensor imaging study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Premenstrual dysphoric disorder (PMDD) is a depressive disorder triggered by fluctuations of progesterone and estradiol during the luteal phase of the menstrual cycle. Selective progesterone receptor modulation (SPRM), while exerting an antagonistic effect on progesterone and maintaining the estradiol on moderate levels, has shown beneficial effects on the mental symptoms of PMDD. Progesterone is also known for its neuroprotective effects, while synthetic progestins have been suggested to promote myelination. However, the impact of this treatment on white matter neuroanatomy is unexplored. Diffusion tensor imaging was used to collect data on white matter integrity in patients with PMDD, before and after treatment with ulipristal acetate (an SPRM) or placebo, as part of a double-blind randomized controlled-trial. Tract based spatial statistics were performed to investigate SPRM treatment vs. placebo longitudinal effects on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) on the whole white matter skeleton. Voxel-wise analyses indicated no change over time in any white matter microstructure metrics in individuals treated with SPRM versus placebo. Improvement in PMDD symptoms did not correlate with changes in white matter microstructure. In secondary, cross-sectional comparisons during treatment, the SPRM group displayed lower FA and higher MD, RD, and AD in several tracts. The main findings suggest that SPRM treatment did not impact white matter microstructure. However, the between-group differences after treatment call for further investigation on the tracts potentially impacted by progesterone antagonism.
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