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- Hudecova, Miriam, 1971-, et al.
(author)
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Prevalence of diabetes, impaired glucose tolerance and insulin sensitivity in patients with polycystic ovary syndrome - a long term follow-up
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Other publication (other academic/artistic)abstract
- Background: The aim of this long-term follow-up study was to examine glucose tolerance and insulin sensitivity in middle-aged women previously diagnosed with PCOS in comparison with age-matched healthy controls. Methods: Women diagnosed with PCOS between 1987 and 1995 were invited for the study. 84 PCOS patients and 87 control subjects, randomly selected from the general population, participated in the study. Anthropometric and metabolic parameters, including an oral glucose tolerance test, were examined. Results: Eighteen (21.4 %) PCOS patients had type 1 or type 2 diabetes or impaired glucose tolerance at the follow-up investigation, which was significantly more common than in control subjects (4.5 %), p < 0.05. Following the adjustment for BMI, insulin sensitivity measured by the Matsuda insulin sensitivity index was significantly lower in women with PCOS and the insulinogenic index, as a measure of beta-cell function, was elevated in PCOS patients in comparison to control subjects. Furthermore, both women with persisting and resolved PCOS at the follow-up investigation displayed decreased Matsuda insulin sensitivity index and increased insulinogenic index in comparison with control subjects. Women without clinical signs of hyperandrogenism at the index assessment displayed higher fasting insulin and proinsulin plasma concentrations than controls at the follow-up investigation. In addition, they had lower Matsuda insulin sensitivity index and higher insulinogenic index than controls. When adjusted for BMI, there was also a trend towards significantly lower Matsuda insulin sensitivity index and increased insulinogenic index at the follow-up investigation among women who had presented with hyperandrogenism at the index assessment. Conclusion: IGT and type 2 diabetes occurred more often in PCOS patients. Independent of PCOS phenotype at index assessment and persistence of PCOS symptoms at the follow-up investigation, women with PCOS had lower insulin sensitivity and increased beta-cell function in comparison with control subjects.
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- Iliadis, Stavros I, et al.
(author)
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Association between a single nucleotide polymorphism in the hydroxysteroid (11-beta) dehydrogenase 1 gene and postpartum depression symptoms: the role of neuroticism
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Other publication (other academic/artistic)abstract
- BackgroundPostpartum depression is a common psychiatric disorder and numerous studies have assessed its association with psychosocial and biological factors. However, the contribution of genetic factors remains largely unknown. A dysregulated hypothalamus-pituitary-adrenal (HPA) axis and neuroticism associate with depressive symptoms after childbirth. A common genetic variant in the hydroxysteroid (11-beta) dehydrogenase 1 gene (HSD11B1), a component of the HPA-axis, has been recently associated with postpartum depressive symptoms. AimTo examine the association between the single nucleotide polymorphism (SNP) rs12565406 in HSD11B1 and neuroticism, as well as the possible mediatory role of neuroticism in the association between the polymorphism and postpartum depressive symptoms. Materials and MethodsThe present study was conducted as part of the BASIC-project and included 771 women. Self-administered questionnaires were sent to study participants, containing the Edinburgh Postnatal Depression Scale (EPDS) at six weeks postpartum and questions on demographic variables at pregnancy week 17 and 32 and at six weeks postpartum, as well as the Swedish universities Scale of Personality (SSP) at pregnancy week 32. Blood samples for genetic analyses were collected. ResultsSixty-five women (8.6%) reported depressive symptoms six weeks postpartum. Study subjects with EPDS ≥ 12 had higher scores on neuroticism compared to controls. Women who were homozygous for the major allele (GG) presented with higher EPDS score postpartum and scored higher in neuroticism, compared to T carriers. Linear regression models with log transformed EPDS score as the dependent variable and the rs12565406 genotype (GG vs. TG/TT) as the independent variable showed an association between the GG genotype and depressive symptoms. When neuroticism was introduced in the model, it was associated with EPDS score, whereas the association between the GG genotype and EPDS became borderline significant. Results were unaltered after adjustment for possible confounders. A path analysis on these variables revealed that neuroticism had a mediatory role in the association between the SNP and EPDS score. ConclusionsNeuroticism had a mediatory role in the association between the HSD11B1 rs12565406 SNP and postpartum depression. Future studies are needed to ascertain whether neuroticism can be used as an easily assessed intermediate phenotype that can reflect the genetic risk of PPD.
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- Immenschuh, Jana, et al.
(author)
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Long-term effects of early life stress on Cyp19a1 mRNA expression and DNA methylation levels in male rats
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Other publication (other academic/artistic)abstract
- Early life stress (ELS) raises the risk of developing mental disorders later in life by inducing lasting epigenetic changes that can impact gene expression. Aromatase, the enzyme responsible for the synthesis of estrogen, is highly expressed in the limbic brain, a key circuit in mental wellbeing. Its neuroprotective role has been investigated in relation to brain trauma but not emotional stress. The present study aimed to investigate the effect of ELS on the expression of the aromatase gene (Cyp19a1), and whether a relation can be observed with the methylation of the gene, in the limbic brain of young adult male rats. ELS was modelled by daily maternal separation for 360 minutes (MS360) in the first three postnatal weeks and compared to a control group (MS15). Cyp19a1 mRNA levels in the cingulate cortex (CCX), medial prefrontal cortex (mPFC), hypothalamus, hippocampus, and amygdala, were quantified by real-time qPCR. Additionally, CpG methylation levels in the Cyp19a1 gene were assessed via targeted next generation bisulfite sequencing. Lower levels of Cyp19a1 were found in the mPFC in MS360 rats compared to MS15, while the opposite trend was observed in the amygdala. Additionally, higher methylation levels were observed in CpGs of intron 2 in the mPFC of MS360 compared with MS15 rats. The methylation levels of intron 2 were negatively correlated with gene expression in the mPFC of MS15 rats, while the correlation was positive for MS360 rats. These findings suggest that ELS might exert a region-specific, long-term effect on both gene expression and methylation of Cyp19a1, especially in the mPFC, a key regions in stress response regulation.
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- Immenschuh, Jana, et al.
(author)
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Multimodal neuroimaging reveals neural correlates of aromatase availability in the female brain
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Other publication (other academic/artistic)abstract
- Background: Estrogens extend their influence beyond reproduction, having been associated with neural plasticity and therefore the potential to shape the brain. It is unknown if the availability of aromatase, which is responsible for local estrogen synthesis in the brain, is associated with neural morphology. Here the correlation between in vivo brain availability of aromatase, grey and white matter structure, and peripheral levels of estradiol in healthy, young women was investigated.Methods: [11C]cetrozole positron emission tomography was performed together with structural and diffusion magnetic resonance imaging to assess the availability of aromatase, grey and white matter volumes, cortical surface architecture and white matter microstructure, respectively. Bioavailable gonadal hormone levels were measured. Results: Aromatase availability was notably high in the thalamus, hypothalamus, and amygdala, positively correlating with the grey matter volume of these regions. Cortical thickness and gyrification of the prefrontal cortex, as well as white matter properties of the fornix, were associated with aromatase availability. This suggests the impact of estrogens on the grey matter areas to which high aromatase-expressing regions are connected, and projecting white matter tracts, all part of the limbic brain that is often involved in mental disorders. Brain aromatase availability did not correlate with peripheral bioavailable hormone levels, pointing to a unique role of brain-derived estrogens. Conclusions: These findings provide the first evidence of brain morphological characteristics being associated with aromatase availability, shedding light on the impact of estrogens on brain structure.
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